RNA in control Blencowe BJ, Khanna M. Molecular biology: RNA in control. Nature. 2007 May 24; 447 (7143): 391-3. RNA in control Compartmentalization of the splicing machinery in plant cell nuclei Lorkovi? ZJ, Barta A. Compartmentalization of the splicing machinery in plant cell nuclei. Trends Plant Sci. 2004 Dec; 9 (12): 565-8. The cell nucleus is a membrane-surrounded organelle that contains numerous compartments in addition to chromatin. Compartmentalization of the nucleus is now accepted as an important feature for the organization of nuclear processes and for gene expression. Recent studies on nuclear organization of splicing factors in plant cells provide insights into the compartmentalization of the plant cell nuclei and conservation of nuclear compartments between plants and metazoans. Compartmentalization of the splicing machinery in plant cell nuclei Pre-mRNA splicing in higher plants Lorkovi? ZJ, Wieczorek Kirk DA, Lambermon MH, Filipowicz W. Pre-mRNA splicing in higher plants. Trends Plant Sci. 2000 Apr; 5 (4): 160-7. Most plant mRNAs are synthesized as precursors containing one or more intervening sequences (introns) that are removed during the process of splicing. The basic mechanism of spliceosome assembly and intron excision is similar in all eukaryotes. However, the recognition of introns in plants has some unique features, which distinguishes it from the reactions in vertebrates and yeast. Recent progress has occurred in characterizing the splicing signals in plant pre-mRNAs, in identifying the mutants affected in splicing and in discovering new examples of alternatively spliced mRNAs. In combination with information provided by the Arabidopsis genome-sequencing project, these studies are contributing to a better understanding of the splicing process and its role in the regulation of gene expression in plants. Pre-mRNA splicing in higher plants Plant serine/arginine-rich proteins and their role in pre-mRAN spicing Reddy AS. Plant serine/arginine-rich proteins and their role in pre-mRNA splicing. Trends Plant Sci. 2004 Nov; 9 (11): 541-7. Pre-messenger RNA (pre-mRNA) splicing, a process by which mature mRNAs are generated by excision of introns and ligation of exons, is an important step in the regulation of gene expression in all eukaryotes. Selection of alternative splice sites in a pre-mRNA generates multiple mRNAs from a single gene that encode structurally and functionally distinct proteins. Alternative splicing of pre-mRNAs contributes greatly to the proteomic complexity of plants and animals and increases the coding potential of a genome. However, the mechanisms that regulate constitutive and alternative splicing of pre-mRNA are not understood in plants. A serine/arginine-rich (SR) family of proteins is implicated in constitutive and alternative splicing of pre-mRNAs. Here I review recent progress in elucidating the roles of serine/arginine-rich proteins in pre-mRNA splicing. Plant serine/arginine-rich proteins and their role in pre-mRAN spicing Alternative splicing and proteome diversity in plants: the tip of the iceberg has just emerged Kazan K. Alternative splicing and proteome diversity in plants: the tip of the iceberg has just emerged. Trends Plant Sci. 2003 Oct;8(10):468-71. Alternative splicing has recently emerged as one of the most significant generators of functional complexity in several relatively well-studied animal genomes, but little is known about the extent of this phenomenon in higher plants. However, recent computational and experimental studies discussed here suggest that alternative splicing probably plays a far more significant role in the generation of proteome diversity in plants than was previously thought. Alternative splicing and proteome diversity in plants Genome-wide natural antisense transcription: coupling its regulation to its different regulatory mechanisms Lapidot M, Pilpel Y. Genome-wide natural antisense transcription: coupling its regulation to its different regulatory mechanisms. EMBO Rep. 2006 Dec; 7 (12): 1216-22. Many genomic loci contain transcription units on both strands, therefore two oppositely oriented transcripts can overlap. Often, one strand codes for a protein, whereas the transcript from the other strand is non-encoding. Such natural antisense transcripts (NATs) can negatively regulate the conjugated sense transcript. NATs are highly prevalent in a wide range of species--for example, around 15% of human protein-encoding genes have an associated NAT. The regulatory mechanisms by which NATs act are diverse, as are the means to control their expression. Here, we review the current understanding of NAT function and its mechanistic basis, which has been gathered from both individual gene cases and genome-wide studies. In parallel, we survey findings about the regulation of NAT transcription. Finally, we hypothesize that the regulation of antisense transcription might be tailored to its mode of action. According to this model, the observed relationship between the expression patterns of NATs and their targets might indicate the regulatory mechanism that is in action. Genome-wide natural antisense transcription-coupling its regulation to its different regulatory mechanisms Plant snoRNAs: functional evolution and new models of gene expression Brown JW, Echeverria M, Qu LH. Plant snoRNAs: functional evolution and new modes of gene expression. Trends Plant Sci. 2003 Jan; 8 (1): 42-9. Small nucleolar RNAs (snoRNAs) are a well-characterized family of non-coding RNAs whose main function is rRNA modification. The diversity and complexity of this gene family continues to expand with the discovery of snoRNAs with non-rRNA or unknown targets. Plants contain more snoRNAs than other eukaryotes and have developed novel expression and processing strategies. The increased number of modifications, which will influence ribosome function, and the novel modes of expression might reflect the environmental conditions to which plants are exposed. Polyploidy and chromosomal rearrangements have generated multiple copies of snoRNA genes, allowing the generation of new snoRNAs for selection. The large snoRNA family in plants is an ideal model for investigation of mechanisms of evolution of gene families in plants. MicroRNAs: Genomics, Biogenesis, Mechanism, and Function David P. Bartel. MicroRNAs: Genomics, Biogenesis, Mechanism, and Function. Cell Volume 116, Issue 2, 23 January 2004, Pages 281-297 MicroRNAs (miRNAs) are endogenous 22 nt RNAs that can play important regulatory roles in animals and plants by targeting mRNAs for cleavage or translational repression. Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes. Let Me Count the Ways: Mechanisms of Gene Regulation by miRNAs and siRNAs Ligang Wu and Joel G. Belasco Let Me Count the Ways: Mechanisms of Gene Regulation by miRNAs and siRNAs. Molecular Cell. Volume 29, Issue 1, 18 January 2008, Pages 1-7 The downregulation of gene expression by miRNAs and siRNAs is a complex process involving both translational repression and accelerated mRNA turnover, each of which appears to occur by multiple mechanisms. Moreover, under certain conditions, miRNAs are also capable of activating translation. A variety of cellular proteins have been implicated in these regulatory mechanisms, yet their exact roles remain largely unresolved. MicroRNAs: Genomics, Biogenesis, Mechanism, and Fu Let Me Count the Ways: Mechanisms of Gene Regulati
the expanding world of small RNAs Grosshans H, Filipowicz W. Molecular biology: the expanding world of small RNAs. Nature. 2008 Jan 24; 451 (7177): 414-6. the expanding world of small RNAs Impact of small RNAs Obernosterer G, Meister G, Poy MN, Kuras A. The impact of small RNAs. Microsymposium on small RNAs. EMBO Rep. 2007 Jan; 8 (1): 23-7. Epub 2006 Dec 15. Impact of small RNAs Small RNAs as big players in plant abiotic stress response and nutrient deprivation Sunkar R, Chinnusamy V, Zhu J, Zhu JK. Small RNAs as big players in plant abiotic stress responses and nutrient deprivation. Trends Plant Sci. 2007 Jul; 12 (7): 301-9. Epub 2007 Jun 18. Abiotic stress is one of the primary causes of crop losses worldwide. Much progress has been made in unraveling the complex stress response mechanisms, particularly in the identification of stress responsive protein-coding genes. In addition to protein coding genes, recently discovered microRNAs (miRNAs) and endogenous small interfering RNAs (siRNAs) have emerged as important players in plant stress responses. Initial clues suggesting that small RNAs are involved in plant stress responses stem from studies showing stress regulation of miRNAs and endogenous siRNAs, as well as from target predictions for some miRNAs. Subsequent studies have demonstrated an important functional role for these small RNAs in abiotic stress responses. This review focuses on recent advances, with emphasis on integration of small RNAs in stress regulatory networks. Small RNAs as big players in plant abiotic stress response and nutrient deprivation RNA silencing: small RNAs as ubiquitous regulators of gene expression Voinnet O. RNA silencing: small RNAs as ubiquitous regulators of gene expression. Curr Opin Plant Biol. 2002 Oct; 5 (5): 444-51. 'RNA silencing' is the suppression of gene expression through nucleotide sequence-specific interactions that are mediated by RNA. Initially identified as an immune system that is targeted against transposons and viruses, RNA silencing is emerging as a fundamental regulatory process that is likely to affect many layers of endogenous gene expression in most, if not all, eukaryotes. RNA silencing-small RNAs as ubiquitous regulators of gene expression Specialization and evolution of endogenous small RNA pathways Chapman EJ, Carrington JC. Specialization and evolution of endogenous small RNA pathways. Nat Rev Genet. 2007 Nov; 8 (11): 884-96. The specificity of RNA silencing is conferred by small RNA guides that are processed from structured RNA or dsRNA. The core components for small RNA biogenesis and effector functions have proliferated and specialized in eukaryotic lineages, resulting in diversified pathways that control expression of endogenous and exogenous genes, invasive elements and viruses, and repeated sequences. Deployment of small RNA pathways for spatiotemporal regulation of the transcriptome has shaped the evolution of eukaryotic genomes and contributed to the complexity of multicellular organisms. Specialization and evolution of endogenous small RNA pathways Targets of RNA-directed DNA methylation Matzke M, Kanno T, Huettel B, Daxinger L, Matzke AJ. Targets of RNA-directed DNA methylation. Curr Opin Plant Biol. 2007 Oct; 10 (5): 512-9. Epub 2007 Aug 16. RNA-directed DNA methylation contributes substantially to epigenetic regulation of the plant genome. Methylation is guided to homologous DNA target sequences by 24 nt 'heterochromatic' small RNAs produced by nucleolar-localized components of the RNAi machinery and a plant-specific RNA polymerase, Pol IV. Plants contain unusually large and diverse populations of small RNAs, many of which originate from transposons and repeats. These sequences are frequent targets of methylation, and they are able to bring plant genes in their vicinity under small RNA-mediated control. RNA-directed DNA methylation can be removed by enzymatic demethylation, providing plants with a versatile system that facilitates epigenetic plasticity. In addition to subduing transposons, RNA-directed DNA methylation has roles in plant development and, perhaps, stress responses. Targets of RNA-directed DNA methylation Signaling in gene silencing Signaling in gene silencing Nucleolar dominance and silencing of transcription Pikaard CS. Nucleolar dominance and silencing of transcription. Trends Plant Sci. 1999 Dec; 4 (12): 478-483. Nucleolar dominance is a phenomenon in plant and animal hybrids whereby one parental set of ribosomal RNA (rRNA) genes is transcribed, but the hundreds of rRNA genes inherited from the other parent are silent. The phenomenon gets it name because only transcriptionally active rRNA genes give rise to a nucleolus, the site of ribosome assembly. Nucleolar dominance provided the first clear example of DNA methylation and histone deacetylation acting in partnership in a gene-silencing pathway. However, the sites of chromatin modification and the ways in which one set of rRNA genes are targeted for repression remain unclear. Another unresolved question is whether the units of regulation are the individual rRNA genes or the multi-megabase chromosomal domains that encompass the rRNA gene clusters. Nucleolar dominance and silencing of transcription Small RNAs and transposon silencing in plants Hidetaka Ito. Small RNAs and transposon silencing in plants. Develop. Growth Differ., 2011. doi: 10.1111/j.1440-169X.2011.01309.x Transposons are highly conserved in plants and have created a symbiotic relationship with the host genome. An important factor of the successful communication between transposons and host plants is epigenetic modifications including DNA methylation and the modifications of the histone tail. In plants, small interfering RNAs (siRNAs) are responsible for RNA-directed DNA methylation (RdDM) that suppresses transposon activities. Although most transposons are silent in their host plants, certain genomic shocks, such as an environmental stress or a hybridization event, might trigger transposon activation. Further, since transposons can affect the regulation mechanisms of host genes, it is possible that transposons have co-evolved as an important mechanism for plant development and adaptation. Recent new findings reveal that siRNAs control not only transcriptional activation, but also suppress transgenerational transposition of mobile elements making siRNAs critically important towards maintaining genome stability. Together these data suggest host-mediated siRNA regulation of transposons appears to have been adapted for controlling essential systems of plant development, morphogenesis, and reproduction. Small RNAs and transposon silencing in plants.pdf
The silence of genes Hunter P. The silence of genes. Is genomic imprinting the software of evolution or just a battleground for gender conflict? EMBO Rep. 2007 May; 8 (5): 441-3. The silence of genes Return to the RNAi world: rethinking gene expression and evolution Mello CC. Return to the RNAi world: rethinking gene expression and evolution. Cell Death Differ. 2007 Dec; 14 (12): 2013-20. Thanks to the Nobel Foundation for permission to publish this Lecture. Here we report the transcript of the lecture delivered by Professor Craig C Mello at the Nobel Prize ceremony. Professor Mello vividly describes the years of research that led to the discovery of RNA interference and the molecular mechanisms that regulate this fundamental cellular process. The turning point of discoveries and the role played by all his colleagues and collaborators are described, making this a wonderful report of the adventure of research. The lecture explains in simple language the importance of this discovery that has added a great level of complexity to the way cells regulate protein levels; moreover, it points out the beauty and importance of Caenorhabditis elegans as a model organism and how the use of this model has greatly contributed to the advance of science. Finally, Professor Mello leaves us with a number of questions that his research has raised and that will require years of future research to be answered. Return to the RNAi world-rethinking gene expression and evolution RNAi: a defensive RNA-silencing against viruses and transposable elements Buchon N, Vaury C. RNAi: a defensive RNA-silencing against viruses and transposable elements. Heredity. 2006 Feb; 96 (2): 195-202. RNA silencing is a form of nucleic-acid-based immunity, targeting viruses and genomic repeated sequences. First documented in plants and invertebrate animals, this host defence has recently been identified in mammals. RNAi is viewed as a conserved ancient mechanism protecting genomes from nucleic acid invaders. However, these tamed sequences are known to occasionally escape this host surveillance and invade the genome of their host. This response is consistent with the overall idea that parasitic sequences compete with cells to systematically counter host defences. Using examples taken from the current literature, we illustrate the dynamic move-countermove game played between these two protagonists, the host cell and its parasitic sequences, and discuss the consequences of this game on genome stability. RNAi-a defensive RNA-silencing against viruses and transposable elements Chromatin-based silenceing mechanism Bender J. Chromatin-based silencing mechanisms. Curr Opin Plant Biol. 2004 Oct; 7 (5): 521-6. Eukaryotic genomes are organized into regions of transcriptionally active euchromatin and transcriptionally inactive heterochromatin. In plant genomes, heterochromatin is marked by methylation of cytosine and methylation of histone H3 at lysine 9. Heterochromatin formation is targeted to transposons as a means of defending the host genome against the deleterious effects of these sequences. Heterochromatin is directed to transposon sequences by transposon-derived aberrant RNA species and functions to prevent unwanted transcription and movement. Formation of heterochromatin at rRNA-encoding genes and centromere-associated repeats might also involve an RNA-based mechanism that is designed to stabilize these potentially labile structures. Chromatin-based silenceing mechanism Role of histone and DNA methylation in gene regulation Vaillant I, Paszkowski J. Role of histone and DNA methylation in gene regulation. Curr Opin Plant Biol. 2007 Oct; 10 (5): 528-33. Epub 2007 Aug 9. Transcription is known to be regulated by given chromatin states, distinguished as transcriptionally active euchromatin and silent heterochromatin. In plants, silencing in heterochromatin is associated with hypermethylation of DNA and specific covalent modifications of histone H3. Several lines of evidence have suggested that maintenance of DNA methylation patterns at CG sequences is responsible for the formation of stable and thus heritable activity states termed epialleles. By contrast, histone modification and DNA methylation outside CGs confer the flexibility of transcriptional regulation necessary for plant development and adaptive responses to the environment. Recent studies have refined our understanding of the biological significance of and the molecular mechanisms involved in the interplay between DNA and histone H3 methylation. Role of histone and DNA methylation in gene regulation DNA-RNA-protein gang together in silence Stokes T. DNA-RNA-protein gang together in silence. Trends Plant Sci. 2003 Feb; 8 (2): 53-5. Two recent reports demonstrate interdependence between DNA and histone methylation in Arabidopsis. ddm1 (decrease in DNA methylation 1) mutants switch histone methylation from a form associated with inactive chromatin to a form connected to actively transcribed genomic regions. The loss of DNA methylation and shift in histone methylation cause transcriptional derepression of heterochromatic regions. In a related report, small RNAs in Schizosaccharomyces pombe mark histone methylation to form heterochromatin, suggesting that methylation systems work alongside RNA metabolism. DNA-RNA-protein gang together in silence RNA interference against viruses: strike and counterstrike Haasnoot J, Westerhout EM, Berkhout B. RNA interference against viruses: strike and counterstrike. Nat Biotechnol. 2007 Dec; 25 (12): 1435-43. RNA interference (RNAi) is a conserved sequence-specific, gene-silencing mechanism that is induced by double-stranded RNA. RNAi holds great promise as a novel nucleic acid-based therapeutic against a wide variety of diseases, including cancer, infectious diseases and genetic disorders. Antiviral RNAi strategies have received much attention and several compounds are currently being tested in clinical trials. Although induced RNAi is able to trigger profound and specific inhibition of virus replication, it is becoming clear that RNAi therapeutics are not as straightforward as we had initially hoped. Difficulties concerning toxicity and delivery to the right cells that earlier hampered the development of antisense-based therapeutics may also apply to RNAi. In addition, there are indications that viruses have evolved ways to escape from RNAi. Proper consideration of all of these issues will be necessary in the design of RNAi-based therapeutics for successful clinical intervention of human pathogenic viruses. RNA interference against viruses-strike and counterstrike RNA silencing and antiviral defence in plants Wang MB , Metzlaff M. RNA silencing and antiviral defense in plants. Curr Opin Plant Biol. 2005 Apr; 8 (2): 216-22. Much progress has been made recently in identifying the molecular components of RNA silencing in plants, and in understanding their roles in the biogenesis of small interfering RNAs and microRNAs, in RNA-directed DNA methylation, and in RNA-mediated antiviral defense. However, many crucial questions remain unanswered. What are the molecular bases of sense and antisense transgene-mediated silencing? Why does silencing only appear to spread through transgenes? Plant viruses encode silencing suppressors to counteract host RNA silencing, and some of these suppressors affect microRNA accumulation and function and hence normal plant development. Is viral pathogenicity determined, partly or entirely, by their silencing suppressor activity? RNA silencing and antiviral defence in plants RNA silencing bridging the gaps in wheat extracts Voinnet O. RNA silencing bridging the gaps in wheat extracts. Trends Plant Sci. 2003 Jul; 8 (7): 307-9. In plants, RNA silencing plays important roles in antiviral defence, genome integrity and development. This process involves nucleotide sequence-specific interactions that are mediated by small RNA molecules of 21-25 nucleotides. Although the core biochemical reactions of RNA silencing have been well characterized in animals, such information was crucially missing in plants. Recent work now addresses this question and reveals an overall similarity between the plant and animal RNA-silencing pathways, as well as some intriguing plant-specific aspects. RNA silencing bridging the gaps in wheat extracts RNA silencing in plants-defense and counterdefense Vance V, Vaucheret H. RNA silencing in plants--defense and counterdefense. Science. 2001 Jun 22; 292 (5525): 2277-80. RNA silencing is a remarkable type of gene regulation based on sequence-specific targeting and degradation of RNA. The term encompasses related pathways found in a broad range of eukaryotic organisms, including fungi, plants, and animals. In plants, it serves as an antiviral defense, and many plant viruses encode suppressors of silencing. The emerging view is that RNA silencing is part of a sophisticated network of interconnected pathways for cellular defense, RNA surveillance, and development and that it may become a powerful tool to manipulate gene expression experimentally. RNA silencing in plants-defense and counterdefense Strategies for silencing human disease using RNA interference Kim DH, Rossi JJ. Strategies for silencing human disease using RNA interference. Nat Rev Genet. 2007 Mar; 8 (3): 173-84. Since the first description of RNA interference (RNAi) in animals less than a decade ago, there has been rapid progress towards its use as a therapeutic modality against human diseases. Advances in our understanding of the mechanisms of RNAi and studies of RNAi in vivo indicate that RNAi-based therapies might soon provide a powerful new arsenal against pathogens and diseases for which treatment options are currently limited. Recent findings have highlighted both promise and challenges in using RNAi for therapeutic applications. Design and delivery strategies for RNAi effector molecules must be carefully considered to address safety concerns and to ensure effective, successful treatment of human diseases. Strategies for silencing human disease using RNA interference Role of short RNAs in gene silencing Waterhouse PM, Wang MB, Finnegan EJ. Role of short RNAs in gene silencing. Trends Plant Sci. 2001 Jul; 6 (7): 297-301. Recent research has revealed the existence of an elegant defence mechanism in plants and lower eukaryotes. The mechanism, known in plants as post-transcriptional gene silencing, works through sequence-specific degradation of RNA. It appears to be directed by double-stranded RNA, associated with the production of short 21-25 nt RNAs, and spread through the plant by a diffusible signal. The short RNAs are implicated as the guides for both a nuclease complex that degrades the mRNA and a methyltransferase complex that methylates the DNA of silenced genes. It has also been suggested that these short RNAs might be the mobile silencing signal, a suggestion that has been challenged recently. Role of short RNAs in gene silencing
Functions of microRNAs and the related small RNAs in plants Mallory AC, Vaucheret H. Functions of microRNAs and related small RNAs in plants. Nat Genet. 2006 Jun;38 Suppl: S31-6. MicroRNAs (miRNAs) and short interfering RNAs (siRNAs), 20- to 27-nt in length, are essential regulatory molecules that act as sequence-specific guides in several processes in most eukaryotes (with the notable exception of the yeast Saccharomyces cerevisiae). These processes include DNA elimination, heterochromatin assembly, mRNA cleavage and translational repression. This review focuses on the regulatory roles of plant miRNAs during development, in the adaptive response to stresses and in the miRNA pathway itself. This review also covers the regulatory roles of two classes of endogenous plant siRNAs, ta-siRNAs and nat-siRNAs, which participate in post-transcriptional control of gene expression. Functions of microRNAs and the related small RNAs in plants microRNA regulation of gene expression in plants Dugas DV, Bartel B. MicroRNA regulation of gene expression in plants. Curr Opin Plant Biol. 2004 Oct; 7 (5): 512-20. It has only been a few years since we began to appreciate that microRNAs provide an unanticipated level of gene regulation in both plants and metazoans. The high level of complementarity between plant microRNAs and their target mRNAs has allowed rapid progress towards the elucidation of their varied biological functions. MicroRNAs have been shown to regulate diverse developmental processes, including organ separation, polarity, and identity, and to modulate their own biogenesis and function. Recently, they have also been implicated in some processes outside of plant development. microRNA regulation of gene expression in plants The evolution of gene regulation by transcription factors and microRNAs Chen K, Rajewsky N. The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet. 2007 Feb; 8 (2): 93-103. Changes in the patterns of gene expression are widely believed to underlie many of the phenotypic differences within and between species. Although much emphasis has been placed on changes in transcriptional regulation, gene expression is regulated at many levels, all of which must ultimately be studied together to obtain a complete picture of the evolution of gene expression. Here we compare the evolution of transcriptional regulation and post-transcriptional regulation that is mediated by microRNAs, a large class of small, non-coding RNAs in plants and animals, focusing on the evolution of the individual regulators and their binding sites. As an initial step towards integrating these mechanisms into a unified framework, we propose a simple model that describes the transcriptional regulation of new microRNA genes. The evolution of gene regulation by transcription factors and microRNAs Mechanisms of post-transcriptional regulation by microRNAs: are the answer in sight? Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet. 2008 Feb; 9 (2): 102-14. MicroRNAs constitute a large family of small, approximately 21-nucleotide-long, non-coding RNAs that have emerged as key post-transcriptional regulators of gene expression in metazoans and plants. In mammals, microRNAs are predicted to control the activity of approximately 30% of all protein-coding genes, and have been shown to participate in the regulation of almost every cellular process investigated so far. By base pairing to mRNAs, microRNAs mediate translational repression or mRNA degradation. This Review summarizes the current understanding of the mechanistic aspects of microRNA-induced repression of translation and discusses some of the controversies regarding different modes of microRNA function. Mechanisms of post-transcriptional regulation by microRNAs MicroRNAs: something important between the genes Mallory AC, Vaucheret H. MicroRNAs: something important between the genes. Curr Opin Plant Biol. 2004 Apr; 7 (2): 120-5. Non-coding small endogenous RNAs, of 21-24 nucleotides in length, have recently emerged as important regulators of gene expression in both plants and animals. At least three categories of small RNAs exist in plants: short interfering RNAs (siRNAs) deriving from viruses or transgenes and mediating virus resistance or transgene silencing via RNA degradation; siRNAs deriving from transposons or transgene promoters and controlling transposon and transgene silencing probably via chromatin changes; and microRNAs (miRNAs) deriving from intergenic regions of the genome and regulating the expression of endogenous genes either by mRNA cleavage or translational repression. The disruption of miRNA-mediated regulation causes developmental abnormalities in plants, demonstrating that miRNAs play an important role in the regulation of developmental decisions. MicroRNAs-something important between the genes MicroRNA biogenesis: coordinated cropping and dicing Kim VN. MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol. 2005 May; 6 (5): 376-85. The recent discovery of microRNAs (miRNAs) took many by surprise because of their unorthodox features and widespread functions. These tiny, approximately 22-nucleotide, RNAs control several pathways including developmental timing, haematopoiesis, organogenesis, apoptosis, cell proliferation and possibly even tumorigenesis. Among the most pressing questions regarding this unusual class of regulatory miRNA-encoding genes is how miRNAs are produced in cells and how the genes themselves are controlled by various regulatory networks. MicroRNA biogenesis-coordinated cropping and dicing Prediction of plant microRNA targets Rhoades MW, Reinhart BJ, Lim LP, Burge CB, Bartel B, Bartel DP. Prediction of plant microRNA targets. Cell. 2002 Aug 23;110(4):513-20. We predict regulatory targets for 14 Arabidopsis microRNAs (miRNAs) by identifying mRNAs with near complementarity. Complementary sites within predicted targets are conserved in rice. Of the 49 predicted targets, 34 are members of transcription factor gene families involved in developmental patterning or cell differentiation. The near-perfect complementarity between plant miRNAs and their targets suggests that many plant miRNAs act similarly to small interfering RNAs and direct mRNA cleavage. The targeting of developmental transcription factors suggests that many plant miRNAs function during cellular differentiation to clear key regulatory transcripts from daughter cell lineages. Prediction of plant microRNA targets Developmental role of microRNA in plants Kidner CA , Martienssen RA. The developmental role of microRNA in plants. Curr Opin Plant Biol. 2005 Feb; 8 (1): 38-44. MicroRNAs (miRNAs) are single-stranded RNA molecules of around 22 nucleotides (nt) in length that are associated with the RNA-induced silencing complex (RISC). They play an important role in plant development, either by targeting mRNA for cleavage or by inhibiting translation. Over the past year, the list of known miRNAs, confirmed targets and developmental effects has expanded, as has the realization that they are conserved during evolution and that small RNAs can play a direct role in cell-cell signaling. Developmental role of microRNA in plants Encountering microRNAs in cell fate signalling Karp X, Ambros V. Developmental biology. Encountering microRNAs in cell fate signaling. Science. 2005 Nov 25; 310 (5752): 1288-9. Encountering microRNAs in cell fate signalling
Perceptions of epigenetics Bird A. Perceptions of epigenetics. Nature. 2007 May 24; 447 (7143): 396-8. Geneticists study the gene; however, for epigeneticists, there is no obvious 'epigene'. Nevertheless, during the past year, more than 2,500 articles, numerous scientific meetings and a new journal were devoted to the subject of epigenetics. It encompasses some of the most exciting contemporary biology and is portrayed by the popular press as a revolutionary new science--an antidote to the idea that we are hard-wired by our genes. So what is epigenetics? Perceptions of epigenetics Epigenetic inheritance in plants Henderson IR, Jacobsen SE. Epigenetic inheritance in plants. Nature. 2007 May 24; 447 (7143): 418-24. The function of plant genomes depends on chromatin marks such as the methylation of DNA and the post-translational modification of histones. Techniques for studying model plants such as Arabidopsis thaliana have enabled researchers to begin to uncover the pathways that establish and maintain chromatin modifications, and genomic studies are allowing the mapping of modifications such as DNA methylation on a genome-wide scale. Small RNAs seem to be important in determining the distribution of chromatin modifications, and RNA might also underlie the complex epigenetic interactions that occur between homologous sequences. Plants use these epigenetic silencing mechanisms extensively to control development and parent-of-origin imprinted gene expression. Epigenetic inheritance in plants Passing the message on: inheritance of epigenetic traits Bond DM, Finnegan EJ. Passing the message on: inheritance of epigenetic traits. Trends Plant Sci. 2007 May; 12 (5): 211-6. Epub 2007 Apr 16. Epigenetic modifiers play an important role in genome organization, stability and the control of gene expression. Three research groups that are exploring the transfer of epigenetic information between generations have recently published papers. Mary Alleman et al. have shown that RNA-directed chromatin changes mediate paramutation in maize, and Minoo Rassoulzadegan et al. have demonstrated that RNA also plays a role in paramutation in mice. A new aspect of epigenetic regulation has been revealed by Jean Molinier et al. - they have demonstrated that the memory of exposure to stress is transferred through several generations. Passing the message on-inheritance of epigenetic traits Epigenetics: regulation through repression Wolffe AP, Matzke MA. Epigenetics: regulation through repression. Science. 1999 Oct 15; 286 (5439): 481-6. Epigenetics is the study of heritable changes in gene expression that occur without a change in DNA sequence. Epigenetic phenomena have major economic and medical relevance, and several, such as imprinting and paramutation, violate Mendelian principles. Recent discoveries link the recognition of nucleic acid sequence homology to the targeting of DNA methylation, chromosome remodeling, and RNA turnover. Although epigenetic mechanisms help to protect cells from parasitic elements, this defense can complicate the genetic manipulation of plants and animals. Essential for normal development, epigenetic controls become misdirected in cancer cells and other human disease syndromes. Epigenetics-regulation through repression Inherited epigenetic variation: revisting soft inheritance Richards EJ. Inherited epigenetic variation--revisiting soft inheritance. Nat Rev Genet. 2006 May; 7 (5): 395-401 Phenotypic variation is traditionally parsed into components that are directed by genetic and environmental variation. The line between these two components is blurred by inherited epigenetic variation, which is potentially sensitive to environmental inputs. Chromatin and DNA methylation-based mechanisms mediate a semi-independent epigenetic inheritance system at the interface between genetic control and the environment. Should the existence of inherited epigenetic variation alter our thinking about evolutionary change? Inherited epigenetic variation-revisting soft inheritance Nucleosome destabilization in the epigenetic regulation of gene expression Henikoff S. Nucleosome destabilization in the epigenetic regulation of gene expression. Nat Rev Genet. 2008 Jan; 9 (1): 15-26. Assembly, mobilization and disassembly of nucleosomes can influence the regulation of gene expression and other processes that act on eukaryotic DNA. Distinct nucleosome-assembly pathways deposit dimeric subunits behind the replication fork or at sites of active processes that mobilize pre-existing nucleosomes. Replication-coupled nucleosome assembly appears to be the default process that maintains silent chromatin, counteracted by active processes that destabilize nucleosomes. Nucleosome stability is regulated by the combined effects of nucleosome-positioning sequences, histone chaperones, ATP-dependent nucleosome remodellers, post-translational modifications and histone variants. Recent studies suggest that histone turnover helps to maintain continuous access to sequence-specific DNA-binding proteins that regulate epigenetic inheritance, providing a dynamic alternative to histone-marking models for the propagation of active chromatin. Nucleosome destabilization in the epigenetic regulation of gene expression Arabidopsis epigenetics: when RNA meets chromatin Gendrel A, Colot V. Arabidopsis epigenetics: when RNA meets chromatin. Curr Opin Plant Biol. 2005 Apr; 8 (2): 142-7. Recent work in plants and other eukaryotes has uncovered a major role for RNA interference in silent chromatin formation. The heritability of the silent state through multiple cell division cycles and, in some instances, through meiosis is assured by epigenetic marks. In plants, transposable elements and transgenes provide striking examples of the stable inheritance of repressed states, and are characterized by dense DNA methylation and heterochromatin histone modifications. Arabidopsis is a useful higher eukaryotes model with which to explore the crossroads between silent chromatin and RNA interference both during development and in the genome-wide control of repeat elements. Arabidopsis epigenetics-when RNA meets chromatin Transposable elements and the epigenetic regulation of the genome Slotkin RK, Martienssen R. Transposable elements and the epigenetic regulation of the genome. Nat Rev Genet. 2007 Apr; 8 (4): 272-85. Overlapping epigenetic mechanisms have evolved in eukaryotic cells to silence the expression and mobility of transposable elements (TEs). Owing to their ability to recruit the silencing machinery, TEs have served as building blocks for epigenetic phenomena, both at the level of single genes and across larger chromosomal regions. Important progress has been made recently in understanding these silencing mechanisms. In addition, new insights have been gained into how this silencing has been co-opted to serve essential functions in 'host' cells, highlighting the importance of TEs in the epigenetic regulation of the genome. Transposable elements and the epigenetic regulation of the genome Methyl-CpG-binding domain proteins in plants: interpreters of DNA methylation Zemach A, Grafi G. Methyl-CpG-binding domain proteins in plants: interpreters of DNA methylation. Trends Plant Sci. 2007 Feb; 12 (2): 80-5. Epub 2007 Jan 8. The effect of DNA methylation on various aspects of plant cellular and developmental processes has been well documented over the past 35 years. However, the underlying molecular mechanism interpreting the methylation signal has only recently been explored with the isolation and characterization of the Arabidopsis methyl-CpG-binding domain (MBD) proteins. In this review, we highlight recent advances and present new models concerning Arabidopsis MBD proteins and their possible role in controlling chromatin structure mediated by CpG methylation. Methyl-CpG-binding domain proteins in plants-interpreters of DNA methylation Imprinting-a green variation Berger F. Plant sciences. Imprinting--a green variation. Science. 2004 Jan 23; 303 (5657): 483-5. Imprinting-a green variation
Towards an accurate sequence of the rice genome Delseny M. Towards an accurate sequence of the rice genome. Curr Opin Plant Biol. 2003 Apr; 6 (2): 101-5. Several more- or less-elaborated rice genome sequences have been produced recently using different strategies. It has become possible to compare them and to unravel the major features of the rice genome in terms of nucleotide composition, repeats, gene content and variability. It has also become possible to compare the rice and Arabidopsis genomes and to evaluate rice as a model genome. Towards an accurate sequence of the rice genome Comparing the whole-genome-shotgun and map-based sequences of the rice genome Yu J, Ni P, Wong GK. Comparing the whole-genome-shotgun and map-based sequences of the rice genome. Trends Plant Sci. 2006 Aug; 11 (8): 387-91. Epub 2006 Jul 13. The rice genome has now been sequenced using whole-genome-shotgun and map-based methods. The relative merits of the two methods are the subject of debate, as they were in the human genome project. In this Opinion article, we will show that the serious discrepancies between the resultant sequences are mostly found in the large transposable elements such as copia and gypsy that populate the intergenic regions of plant genomes. Differences in published gene counts and polymorphism rates are similarly resolved by considering how transposable elements affect the sequence analysis. Comparing the whole-genome-shotgun and map-based sequences of the rice genome Diversity in Oryza genus Vaughan DA, Morishima H, Kadowaki K. Diversity in the Oryza genus. Curr Opin Plant Biol. 2003 Apr; 6 (2): 139-46. The pan-tropical wild relatives of rice grow in a wide variety of habitats: forests, savanna, mountainsides, rivers and lakes. The completion of the sequencing of the rice nuclear and cytoplasmic genomes affords an opportunity to widen our understanding of the genomes of the genus Oryza. Research on the Oryza genus has begun to help to answer questions related to domestication, speciation, polyploidy and ecological adaptation that cannot be answered by studying rice alone. The wild relatives of rice have furnished genes for the hybrid rice revolution, and other genes from Oryza species with major impact on rice yields and sustainable rice production are likely to be found. Care is needed, however, when using wild relatives of rice in experiments and in interpreting the results of these experiments. Careful checking of species identity, maintenance of herbarium specimens and recording of Genbank accession numbers of material used in experiments should be standard procedure when studying wild relatives of rice. Diversity in Oryza genus Genome-wide intraspecific DNA-sequence variations in rice Han B, Xue Y. Genome-wide intraspecific DNA-sequence variations in rice. Curr Opin Plant Biol.2003 Apr; 6 (2): 134-8. Genome-wide comparative analysis of the DNA sequences of two major cultivated rice subspecies, Oryza sativa L. ssp indica and Oryza sativa L. ssp japonica, have revealed their extensive microcolinearity in gene order and content. However, deviations from colinearity are frequent owing to insertions or deletions. Intraspecific sequence polymorphisms commonly occur in both coding and non-coding regions. These variations often affect gene structures and may contribute to intraspecific phenotypic adaptations. Genome-wide intraspecific DNA-sequence variations in rice Sequencing the maize genome Martienssen RA, Rabinowicz PD, O'Shaughnessy A, McCombie WR. Sequencing the maize genome. Curr Opin Plant Biol. 2004 Apr; 7 (2): 102-7. Sequencing of complex genomes can be accomplished by enriching shotgun libraries for genes. In maize, gene-enrichment by copy-number normalization (high C(0)t) and methylation filtration (MF) have been used to generate up to two-fold coverage of the gene-space with less than 1 million sequencing reads. Simulations using sequenced bacterial artificial chromosome (BAC) clones predict that 5x coverage of gene-rich regions, accompanied by less than 1x coverage of subclones from BAC contigs, will generate high-quality mapped sequence that meets the needs of geneticists while accommodating unusually high levels of structural polymorphism. By sequencing several inbred strains, we propose a strategy for capturing this polymorphism to investigate hybrid vigor or heterosis. Sequencing the maize genome Genomic diversity in forest tree Savolainen O, Pyhjrvi T. Genomic diversity in forest trees. Curr Opin Plant Biol. 2007 Apr; 10 (2): 162-7. Epub 2007 Feb 9. Forest trees in general are out-crossing, long-lived, and at early stages of domestication. Molecular evolution at neutral sites is very slow because of the long generation times. Transferring information between closely related conifer species is facilitated by high sequence similarity. At the nucleotide level, trees have at most intermediate levels of variation relative to other plants. Importantly, in many species linkage disequilibrium within genes declines within less than 1000 bp. In contrast to the slow rate of neutral evolution, large tree populations respond rapidly to natural selection. Detecting traces of selection may be easier in tree populations than in many other species. Association studies between genotypes and phenotypes are proving to be useful tools for functional genomics. Genomic diversity in forest tree Complex gene families in pine genomes Jumping genes and maize genomics
Comparison of rice and Arabidopsis annotation Schoof H, Karlowski WM. Comparison of rice and Arabidopsis annotation. Curr Opin Plant Biol. 2003 Apr; 6 (2): 106-12. Several versions of the rice genome were published in 2002, providing a first overview of the genome content of this model monocot. At the same time, the genome of the model dicot, Arabidopsis thaliana, reached a new level of annotation as thousands of full-length cDNA sequences were integrated with the genome sequence. Comparison of rice and Arabidopsis annotation The ABCs of comparative genomics in the Brassicaceae: building blocks of crucifer genomes Schranz ME, Lysak MA, Mitchell-Olds T. The ABC's of comparative genomics in the Brassicaceae: building blocks of crucifer genomes. Trends Plant Sci. 2006 Nov; 11 (11): 535-42. Epub 2006 Oct 6. In this review we summarize recent advances in our understanding of phylogenetics, polyploidization and comparative genomics in the family Brassicaceae. These findings pave the way for a unified comparative genomic framework. We integrate several of these findings into a simple system of 24 conserved chromosomal blocks (labeled A-X). The naming, order, orientation and color-coding of these blocks are based on their positions in a proposed ancestral karyotype (n=8), rather than by their position in the reduced genome of Arabidopsis thaliana (n=5). We show how these crucifer building blocks can be rearranged to model the genome structures of A. thaliana, Arabidopsis lyrata, Capsella rubella and Brassica rapa. A framework for comparison between species is timely because several crucifer genome-sequencing projects are underway. The ABCs of comparative genomics in the Brassicaceae-building blocks of crucifer genomes Comparative biology comes into bloom: genomic and genetic comparision of flowering pathways in rice and Arabidopsis Izawa T, Takahashi Y, Yano M. Comparative biology comes into bloom: genomic and genetic comparison of flowering pathways in rice and Arabidopsis. Curr Opin Plant Biol. 2003 Apr; 6 (2): 113-20. Huge advances in plant biology are possible now that we have the complete genome sequences of several flowering plants. Now, genomes can be comprehensively compared and map-based cloning can be performed more easily. Association study is emerging as a powerful method for the functional identification of genes and molecular genetics has begun to reveal the basis of plant diversity. Taking the flowering pathways as an example, we discuss the potential of several approaches to comparative biology. Comparative biology comes into bloom-genomic and genetic comparision of flowering pathways in rice and Arabidopsis Unveiling the molecular arms race between two conflicting genomes in cytoplasmic male sterility Touzet P, Budar F. Unveiling the molecular arms race between two conflicting genomes in cytoplasmic male sterility? Trends Plant Sci. 2004 Dec; 9 (12): 568-70. Cytoplasmic male sterility can be thought of as the product of a genetic conflict between two genomes that have different modes of inheritance. Male sterilizing factors, generally encoded by chimeric mitochondrial genes, can be down-regulated by specific nuclear restorer genes. The recent cloning of a restorer gene in rice and its comparison with restorer genes cloned in petunia and radish could be regarded as the beginning of a general molecular scenario in this peculiar arms race. Unveiling the molecular arms race between two conflicting genomes in cytoplasmic male sterility
The genetic colinearty of rice and other cereals on the basis of genomic sequence analysis Bennetzen JL, Ma J. The genetic colinearity of rice and other cereals on the basis of genomic sequence analysis. Curr Opin Plant Biol. 2003 Apr; 6 (2): 128-33. Small segments of rice genome sequence have been compared with that of the model plant Arabidopsis thaliana and with several closer relatives, including the cereals maize, rice, sorghum, barley and wheat. The rice genome is relatively stable relative to those of other grasses. Nevertheless, comparisons with other cereals have demonstrated that the DNA between cereal genes is highly variable and evolves rapidly. Genic regions have undergone many more small rearrangements than have been revealed by recombinational mapping studies. Tandem gene duplication/deletion is particularly common, but other types of deletions, inversions and translocations also occur. The many thousands of small genic rearrangements within the rice genome complicate but do not negate its use as a model for larger cereal genomes. The genetic colinearty of rice and other cereals on the basis of genomic sequence analysis Updating the crop circle Devos KM. Updating the 'crop circle'. Curr Opin Plant Biol. 2005 Apr; 8 (2): 155-62. Comparative analyses unravel the relationships between genomes of related species. The most comprehensive comparative dataset obtained to date is from the grass family, which contains all of the major cereals. Early studies aimed to identify chromosomal regions that have remained conserved over long evolutionary time periods, but in recent years, researchers have focused more on the extent of colinearity at the DNA-sequence level. The latter studies have uncovered many small rearrangements that disturb colinearity in orthologous chromosome regions. In part, genomes derive their plasticity from genome- and gene-amplification processes. Duplicated gene copies are more likely to escape selective constraints and thus move to other regions of the genome, where they might acquire new functions or become deleted. These rearrangements will affect map applications. The most popular applications, especially since the complete rice genomic sequence has been available, are the use of comparative data in the generation of new markers to tag traits in other species and to identify candidate genes for these traits. The isolation of genes underlying orthologous traits is the first step in conducting comparative functional studies. Updating the crop circle Colinearty and gene density in grass genomes Keller B, Feuillet C. Colinearity and gene density in grass genomes. Trends Plant Sci. 2000 Jun; 5 (6): 246-51. Grasses are the single most important plant family in agriculture. In the past years, comparative genetic mapping has revealed conserved gene order (colinearity) among many grass species. Recently, the first studies at gene level have demonstrated that microcolinearity of genes is less conserved: small scale rearrangements and deletions complicate the microcolinearity between closely related species, such as sorghum and maize, but also between rice and other crop plants. In spite of these problems, rice remains the model plant for grasses as there is limited useful colinearity between Arabidopsis and grasses. However, studies in rice have to be complemented by more intensive genetic work on grass species with large genomes (maize, Triticeae). Gene-rich chromosomal regions in species with large genomes, such as wheat, have a high gene density and are ideal targets for partial genome sequencing. Colinearty and gene density in grass genomes Comparison of genes among cereals Ware D, Stein L. Comparison of genes among cereals. Curr Opin Plant Biol. 2003 Apr; 6 (2): 121-7. Comparison of partially sequenced cereal genomes suggests a mosaic structure consisting of recombinationally active gene-rich islands that are separated by blocks of high-copy DNA. Annotation of the whole rice genome suggests that most, but not all, cereal genes are present within the rice genome and that the high number of reported genes in this genome is probably due to duplications. Within the cereals, macrocolinearity is conserved but, at the level of individual genes, microcolinearity is frequently disrupted. Preliminary evidence from limited comparative analysis of sequenced orthologous genomic segments suggests that local gene amplification and translocation within a plant genome may be linked in some cases. Comparison of genes among cereals Patterns in grass genome evolution Bennetzen JL. Patterns in grass genome evolution. Curr Opin Plant Biol. 2007 Apr; 10 (2): 176-81. Epub 2007 Feb 8. Increasingly comprehensive, species-rich, and large-scale comparisons of grass genome structure have uncovered an even higher level of genomic rearrangement than originally observed by recombinational mapping or orthologous clone sequence comparisons. Small rearrangements are exceedingly abundant, even in comparisons of closely related species. The mechanisms of these small rearrangements, mostly tiny deletions caused by illegitimate recombination, appear to be active in all of the plant species investigated, but their relative aggressiveness differs dramatically in different plant lineages. Transposable element amplification, including the acquisition and occasional fusion of gene fragments from multiple loci, is also common in all grasses studied, but has been a much more major contributor in some species than in others. The reasons for these quantitative differences are not known, but it is clear that they lead to species that have very different levels of genomic instability. Similarly, polyploidy and segmental duplication followed by gene loss are standard phenomena in the history of all flowering plants, including the grasses, but their frequency and final outcomes are very different in different lineages. Now that genomic instability has begun to be characterized in detail across an array of plant species, it is time for comprehensive studies to investigate the relationships between particular changes in genome structure and organismal function or fitness. Patterns in grass genome evolution The rice genome and comparative genomics of higher plants The rice genome and comparative genomics of higher plants
Leafing through the genomes of our major crop plants: strategies for capturing unique information Paterson AH. Leafing through the genomes of our major crop plants: strategies for capturing unique information. Nat Rev Genet. 2006 Mar; 7 (3): 174-84. Crop plants not only have economic significance, but also comprise important botanical models for evolution and development. This is reflected by the recent increase in the percentage of publicly available sequence data that are derived from angiosperms. Further genome sequencing of the major crop plants will offer new learning opportunities, but their large, repetitive, and often polyploid genomes present challenges. Reduced-representation approaches - such as EST sequencing, methyl filtration and Cot-based cloning and sequencing - provide increased efficiency in extracting key information from crop genomes without full-genome sequencing. Combining these methods with phylogenetically stratified sampling to allow comparative genomic approaches has the potential to further accelerate progress in angiosperm genomics. Leafing through the genomes of our major crop plants-strategies for capturing unique information Genomics tools for QTL analysis and gene discovery Borevitz JO, Chory J. Genomics tools for QTL analysis and gene discovery. Curr Opin Plant Biol. 2004 Apr; 7 (2): 132-6. In recent years, several new genomics resources and tools have become available that will greatly assist quantitative trait locus (QTL) mapping and cloning of the corresponding genes. Genome sequences, tens of thousands of molecular markers, microarrays, and knock-out collections are being applied to QTL mapping, facilitating the use of natural accessions for gene discovery. Genomics tools for QTL analysis and gene discovery Tandem gene arrays: a challenge for functional genomics Jander G, Barth C. Tandem gene arrays: a challenge for functional genomics. Trends Plant Sci. 2007 May; 12 (5): 203-10. Epub 2007 Apr 9. In sequenced plant genomes, 15% or more of the identified genes are members of tandem-arrayed gene families. Because mutating only one gene in a duplicated pair often produces no measurable phenotype, this poses a particular challenge for functional analysis. To generate phenotypic knockouts, it is necessary to create deletions that affect multiple genes, select for rare meiotic recombination between tightly linked loci, or perform sequential mutant screens in the same plant line. Successfully implemented strategies include PCR-based screening for fast neutron-induced deletions, selection for recombination between herbicide resistance markers, and localized transposon mutagenesis. Here, we review the relative merits of current genetic approaches and discuss the prospect of site-directed mutagenesis for generating elusive knockouts of tandem-arrayed gene families. Tandem gene arrays-a challenge for functional genomics Re-valuating the relevance of ancenstral shared synteny as a tool for crop improvement Delseny M. Re-evaluating the relevance of ancestral shared synteny as a tool for crop improvement. Curr Opin Plant Biol. 2004 Apr; 7 (2): 126-31. In addition to the Arabidopsis and rice genomic sequences, numerous expressed sequence tags (ESTs) and sequenced tag sites are now available for many species. These tools have made it possible to re-evaluate the extent of synteny and collinearity not only between Arabidopsis and related crops or between rice and other cereals but also between Arabidopsis and rice, between Arabidopsis and other dicots, and between cereals other than rice. Major progress in describing synteny relies on statistical tests. Overall, the data point to the occurrence of ancestral genome fragments in which a framework of common markers can be recognised. Micro-synteny studies reveal numerous rearrangements, which are likely to complicate map-based cloning strategies that use information from a model genome. Re-valuating the relevance of ancenstral shared synteny as a tool for crop improvement Synteny: recent advances and future prospects Schmidt R. Synteny: recent advances and future prospects. Curr Opin Plant Biol. 2000 Apr; 3 (2): 97-102. Their small sizes have meant that the Arabidopsis and rice genomes are the best-studied of all plant genomes. Although even closely related plant species can show large variations in genome size, extensive genome colinearity has been established at the genetic level and recently also at the gene level. This allows the transfer of information and resources assembled for rice and Arabidopsis to be used in the genome analysis of many other plants. Synteny-recent advances and future prospects Synergy between sequence and size in large-scale genomics Gregory TR. Synergy between sequence and size in large-scale genomics. Nat Rev Genet. 2005 Sep; 6 (9): 699-708. Until recently the study of individual DNA sequences and of total DNA content (the C-value) sat at opposite ends of the spectrum in genome biology. For gene sequencers, the vast stretches of non-coding DNA found in eukaryotic genomes were largely considered to be an annoyance, whereas genome-size researchers attributed little relevance to specific nucleotide sequences. However, the dawn of comprehensive genome sequencing has allowed a new synergy between these fields, with sequence data providing novel insights into genome-size evolution, and with genome-size data being of both practical and theoretical significance for large-scale sequence analysis. In combination, these formerly disconnected disciplines are poised to deliver a greatly improved understanding of genome structure and evolution. Synergy between sequence and size in large-scale genomics Transposable elements and the plant pan-genomes Morgante M, De Paoli E, Radovic S. Transposable elements and the plant pan-genomes. Curr Opin Plant Biol. 2007 Apr; 10 (2): 149-55. Epub 2007 Feb 14. The comparative sequencing of several grass genomes has revealed that transposable elements are largely responsible for extensive variation in both intergenic and local genic content, not only between closely related species but also among individuals within a species. These observations indicate that a single genome sequence might not reflect the entire genomic complement of a species, and prompted us to introduce the concept of the plant pan-genome, which includes core genomic features that are common to all individuals and a dispensable genome composed of partially shared and/or non-shared DNA sequence elements. Uncovering the intriguing nature of the dispensable genome, namely its composition, origin and function, represents a step forward towards an understanding of the processes that generate genetic diversity and phenotypic variation. The developing view of transcriptional regulation as a complex and modular system, in which long-range interactions and the involvement of transposable elements are frequently observed, lends support to the possibility of an important functional role for the dispensable genome and could make it less dispensable than previously thought. Transposable elements and the plant pan-genomes Flux an important, but neglected, component of functional genomics Fernie AR , Geigenberger P, Stitt M. Flux an important, but neglected, component of functional genomics. Curr Opin Plant Biol. 2005 Apr; 8 (2): 174-82. Genomics approaches aimed at understanding metabolism currently tend to involve mainly expression profiling, although proteomics and steady-state metabolite profiling are increasingly being carried out as alternative strategies. These approaches provide rich information on the inventory of the cell. It is, however, of growing importance that such approaches are augmented by sophisticated integrative analyses and a higher-level understanding of cellular dynamics to provide insights into mechanisms that underlie biological processes. We argue the need for, and discuss theoretical and practical aspects of, the determination of metabolic flux as a component of functional genomics. Flux an important, but neglected, component of functional genomics Genomics of sex chromosomes Ming R, Moore PH. Genomics of sex chromosomes. Curr Opin Plant Biol. 2007 Apr ;10 (2): 123-30. Epub 2007 Feb 14. Sex chromosomes in plants and animals are distinctive, not only because of their gender-determining role but also for genomic features that reflect their evolutionary history. The genomic sequences in the ancient sex chromosomes of humans and in the incipient sex chromosomes of medaka, stickleback, papaya, and poplar exhibit unusual features as consequences of their evolution. These include the enormous palindrome structure in human MSY, a duplicated genomic fragment that evolved into a Y chromosome in medaka, and a 700 kb extra telomeric sequence of the W chromosome in poplar. Comparative genomic analysis of ancient and incipient sex chromosomes highlights common features that implicate the selection forces that shaped them, even though evolutionary origin, pace, and fate vary widely among individual sex-determining systems. Genomics of sex chromosomes And then there were many: MADS goes genomic De Bodt S, Raes J, Van de Peer Y, Theissen G. And then there were many: MADS goes genomic. Trends Plant Sci. 2003 Oct; 8 (10): 475-83. During the past decade, MADS-box genes have become known as key regulators in both reproductive and vegetative plant development. Traditional genetics and functional genomics tools are now available to elucidate the expression and function of this complex gene family on a much larger scale. Moreover, comparative analysis of the MADS-box genes in diverse flowering and non-flowering plants, boosted by bioinformatics, contributes to our understanding of how this important gene family has expanded during the evolution of land plants. Therefore, the recent advances in comparative and functional genomics should enable researchers to identify the full range of MADS-box gene functions, which should help us significantly in developing a better understanding of plant development and evolution. And then there were many-MADS goes genomic Plant functional genomics: beyond the parts list Stewart CN Jr. Plant functional genomics: beyond the parts list. Trends Plant Sci. 2005 Dec; 10 (12): 561-2. Epub 2005 Nov 14. Plant functional genomics-beyond the parts list Genomics-deeper and wider in order to understanding plant diversity Genomics-deeper and wider in order to understanding plant diversity The consequences of gene and genome duplication in plants The consequences of gene and genome duplication in plants
Speciation: A new role for reinforcement Smadja C, Butlin R. Speciation: A new role for reinforcement. Heredity. 2006 Jun; 96 (6): 422-3. Speciation-A new role for reinforcement Plant speciation Rieseberg LH, Willis JH. Plant speciation. Science. 2007 Aug 17; 317 (5840): 910-4. Like the formation of animal species, plant speciation is characterized by the evolution of barriers to genetic exchange between previously interbreeding populations. Prezygotic barriers, which impede mating or fertilization between species, typically contribute more to total reproductive isolation in plants than do postzygotic barriers, in which hybrid offspring are selected against. Adaptive divergence in response to ecological factors such as pollinators and habitat commonly drives the evolution of prezygotic barriers, but the evolutionary forces responsible for the development of intrinsic postzygotic barriers are virtually unknown and frequently result in polymorphism of incompatibility factors within species. Polyploid speciation, in which the entire genome is duplicated, is particularly frequent in plants, perhaps because polyploid plants often exhibit ecological differentiation, local dispersal, high fecundity, perennial life history, and self-fertilization or asexual reproduction. Finally, species richness in plants is correlated with many biological and geohistorical factors, most of which increase ecological opportunities. Plant speciation The nature of plant species Rieseberg LH, Wood TE, Baack EJ. The nature of plant species. Nature. 2006 Mar 23; 440 (7083): 524-7. Many botanists doubt the existence of plant species, viewing them as arbitrary constructs of the human mind, as opposed to discrete, objective entities that represent reproductively independent lineages or 'units of evolution'. However, the discreteness of plant species and their correspondence with reproductive communities have not been tested quantitatively, allowing zoologists to argue that botanists have been overly influenced by a few 'botanical horror stories', such as dandelions, blackberries and oaks. Here we analyse phenetic and/or crossing relationships in over 400 genera of plants and animals. We show that although discrete phenotypic clusters exist in most genera ( 80%), the correspondence of taxonomic species to these clusters is poor ( 60%) and no different between plants and animals. Lack of congruence is caused by polyploidy, asexual reproduction and over-differentiation by taxonomists, but not by contemporary hybridization. Nonetheless, crossability data indicate that 70% of taxonomic species and 75% of phenotypic clusters in plants correspond to reproductively independent lineages (as measured by postmating isolation), and thus represent biologically real entities. Contrary to conventional wisdom, plant species are more likely than animal species to represent reproductively independent lineages. The nature of plant species There shall be order. The legacy of Linnaeus in the age of molecular biology Paterlini M. There shall be order. The legacy of Linnaeus in the age of molecular biology. EMBO Rep. 2007 Sep; 8 (9): 814-6. There shall be order DNA barcodes: recent successes and future prospects Dasmahapatra KK, Mallet J. DNA barcodes: recent successes and future prospects. Heredity. 2006 Oct; 97 (4): 254-5. Epub 2006 Jun 21. DNA barcodes-recent successes and future prospects The molecular genetics of crop domestication Doebley JF, Gaut BS, Smith BD. The molecular genetics of crop domestication. Cell. 2006 Dec 29; 127 (7): 1309-21. Ten thousand years ago human societies around the globe began to transition from hunting and gathering to agriculture. By 4000 years ago, ancient peoples had completed the domestication of all major crop species upon which human survival is dependent, including rice, wheat, and maize. Recent research has begun to reveal the genes responsible for this agricultural revolution. The list of genes to date tentatively suggests that diverse plant developmental pathways were the targets of Neolithic genetic tinkering, and we are now closer to understanding how plant development was redirected to meet the needs of a hungry world. The molecular genetics of crop domestication
The evolution of sex-biased genes and sex-biased gene expression Ellegren H, Parsch J. The evolution of sex-biased genes and sex-biased gene expression. Nat Rev Genet. 2007 Sep; 8 (9): 689-98. Epub 2007 Aug 7. Differences between males and females in the optimal phenotype that is favoured by selection can be resolved by the evolution of differential gene expression in the two sexes. Microarray experiments have shown that such sex-biased gene expression is widespread across organisms and genomes. Sex-biased genes show unusually rapid sequence evolution, are often labile in their pattern of expression, and are non-randomly distributed in the genome. Here we discuss the characteristics and expression of sex-biased genes, and the selective forces that shape this previously unappreciated source of phenotypic diversity. Sex-biased gene expression has implications beyond just evolutionary biology, including for medical genetics. The evolution of sex-biased genes and sex-biased gene expression Evolutionary complexity of MADS complexes Rijpkema AS , Gerats T, Vandenbussche M. Evolutionary complexity of MADS complexes. Curr Opin Plant Biol. 2007 Feb; 10 (1): 32-8. Epub 2006 Nov 30. Developmental programs rely on the timely and spatially correct expression of sets of interacting factors, many of which appear to be transcription factors. Examples of these can be found in the MADS-box gene family. This gene family has greatly expanded, particularly in plants, by a range of duplications that have enabled the genes to diversify in structure and function. MADS-box genes appear to have been instrumental in shaping one of the great evolutionary innovations, the true flower, which originated around 120-150 million years ago and led to the enormous radiation of the angiosperms. We propose a shift from analyzing individual gene functions towards studying MADS-box gene function at the subfamily level. This will enable us to distinguish subfunctionalization events from the evolutionary changes that defined floral morphology. Evolutionary complexity of MADS complexes Evolutionary genetics: fight or flinch? Brown JK, Handley RJ. Fight or flinch? Heredity. 2006 Jan; 96 (1): 3-4. Evolutionary genetics-fight or flinch Evolving disease resistance genes Meyers BC, Kaushik S, Nandety RS. Evolving disease resistance genes. Curr Opin Plant Biol. 2005 Apr; 8 (2): 129-34. Defenses against most specialized plant pathogens are often initiated by a plant disease resistance gene. Plant genomes encode several classes of genes that can function as resistance genes. Many of the mechanisms that drive the molecular evolution of these genes are now becoming clear. The processes that contribute to the diversity of R genes include tandem and segmental gene duplications, recombination, unequal crossing-over, point mutations, and diversifying selection. Diversity within populations is maintained by balancing selection. Analyses of whole-genome sequences have and will continue to provide new insight into the dynamics of resistance gene evolution. Evolving disease resistance genes
Chromosome evolution Schubert I. Chromosome evolution. Curr Opin Plant Biol. 2007 Apr; 10 (2): 109-15. Epub 2007 Feb 7. The idea of evolution as a principle for the origin of biodiversity fits all phenomena of life, including the carriers of nuclear inheritance, the chromosomes. Insights into the evolutionary mechanisms that contribute to the shape, size, composition, number and redundancy of chromosomes elucidate the high plasticity of nuclear genomes at the chromosomal level, and the potential for genome modification in the course of breeding processes. Aspects of chromosome fusion, as exemplified by karyotype evolution of relatives of Arabidopsis, have recently received special attention. Chromosome evolution Steps in the evolution of heteromorphic sex chromosomes Charlesworth D, Charlesworth B, Marais G. Steps in the evolution of heteromorphic sex chromosomes. Heredity. 2005 Aug; 95 (2): 118-28. We review some recently published results on sex chromosomes in a diversity of species. We focus on several fish and some plants whose sex chromosomes appear to be 'young', as only parts of the chromosome are nonrecombining, while the rest is pseudoautosomal. However, the age of these systems is not yet very clear. Even without knowing what proportions of their genes are genetically degenerate, these cases are of great interest, as they may offer opportunities to study in detail how sex chromosomes evolve. In particular, we review evidence that recombination suppression occurs progressively in evolutionarily independent cases, suggesting that selection drives loss of recombination over increasingly large regions. We discuss how selection during the period when a chromosome is adapting to its role as a Y chromosome might drive such a process. Steps in the evolution of heteromorphic sex chromosomes Evolutionary genetics: when duplicated gene dont stick to the rules Van de Peer Y. Evolutionary genetics: when duplicated genes don't stick to the rules. Heredity. 2006 Mar; 96 (3): 204-5. when duplicated gene dont stick to the rules Junk DNA as an evolutionary force Bimont C, Vieira C. Genetics: junk DNA as an evolutionary force. Nature. 2006 Oct 5; 443 (7111): 521-4. Junk DNA as an evolutionary force The evolutionary dynamics of plant duplicate genes Moore RC, Purugganan MD. The evolutionary dynamics of plant duplicate genes. Curr Opin Plant Biol. 2005 Apr; 8 (2): 122-8. Given the prevalence of duplicate genes and genomes in plant species, the study of their evolutionary dynamics has been a focus of study in plant evolutionary genetics over the past two decades. The past few years have been a particularly exciting time because recent theoretical and experimental investigations have led to a rethinking of the classic paradigm of duplicate gene evolution. By combining recent advances in genomic analysis with a new conceptual framework, researchers are determining the contributions of single-gene and whole-genome duplications to the diversification of plant species. This research provides insights into the roles that gene and genome duplications play in plant evolution. The evolutionary dynamics of plant duplicate genes The rise and falls of introns Belshaw R, Bensasson D. The rise and falls of introns. Heredity. 2006 Mar; 96 (3): 208-13. There has been a lively debate over the evolution of eukaryote introns: at what point in the tree of life did they appear and from where, and what has been their subsequent pattern of loss and gain? A diverse range of recent research papers is relevant to this debate, and it is timely to bring them together. The absence of introns that are not self-splicing in prokaryotes and several other lines of evidence suggest an ancient eukaryotic origin for these introns, and the subsequent gain and loss of introns appears to be an ongoing process in many organisms. Some introns are now functionally important and there have been suggestions that invoke natural selection for the ancient and recent gain of introns, but it is also possible that fixation and loss of introns can occur in the absence of positive selection. The rise and falls of introns Retrotransposons: central players in the structure, evolution and function of plant geneomes Kumar A, Bennetzen JL. Retrotransposons: central players in the structure, evolution and function of plant genomes. Trends Plant Sci. 2000 Dec;5 (12): 509-10. Retrotransposons-central players in the structure, evolution and function of plant geneomes
Eukaryotic evolution, changes and challenges Embley TM, Martin W. Eukaryotic evolution, changes and challenges. Nature. 2006 Mar 30; 440 (7084): 623-30. The idea that some eukaryotes primitively lacked mitochondria and were true intermediates in the prokaryote-to-eukaryote transition was an exciting prospect. It spawned major advances in understanding anaerobic and parasitic eukaryotes and those with previously overlooked mitochondria. But the evolutionary gap between prokaryotes and eukaryotes is now deeper, and the nature of the host that acquired the mitochondrion more obscure, than ever before. Eukaryotic evolution, changes and challenges Climbing the evolutionary tree- Andrews P Climbing the evolutionary tree- Andrews P Which evolutionar processes influence natural genetic variation for phenotypic traits Mitchell-Olds T, Willis JH, Goldstein DB. Which evolutionary processes influence natural genetic variation for phenotypic traits? Nat Rev Genet. 2007 Nov; 8 (11): 845-56. Although many studies provide examples of evolutionary processes such as adaptive evolution, balancing selection, deleterious variation and genetic drift, the relative importance of these selective and stochastic processes for phenotypic variation within and among populations is unclear. Theoretical and empirical studies from humans as well as natural animal and plant populations have made progress in examining the role of these evolutionary forces within species. Tentative generalizations about evolutionary processes across species are beginning to emerge, as well as contrasting patterns that characterize different groups of organisms. Furthermore, recent technical advances now allow the combination of ecological measurements of selection in natural environments with population genetic analysis of cloned QTLs, promising advances in identifying the evolutionary processes that influence natural genetic variation. Which evolutionar processes influence natural genetic variation for phenotypic traits Phylogenomics and the reconstruction of the tree of life Delsuc F, Brinkmann H, Philippe H. Phylogenomics and the reconstruction of the tree of life. Nat Rev Genet. 2005 May; 6 (5): 361-75. As more complete genomes are sequenced, phylogenetic analysis is entering a new era - that of phylogenomics. One branch of this expanding field aims to reconstruct the evolutionary history of organisms on the basis of the analysis of their genomes. Recent studies have demonstrated the power of this approach, which has the potential to provide answers to several fundamental evolutionary questions. However, challenges for the future have also been revealed. The very nature of the evolutionary history of organisms and the limitations of current phylogenetic reconstruction methods mean that part of the tree of life might prove difficult, if not impossible, to resolve with confidence. Phylogenomics and the reconstruction of the tree of life Variation and constraint in plant evolution and development Kalisz S, Kramer EM. Variation and constraint in plant evolution and development. Heredity. 2008 Feb; 100 (2): 171-7. Epub 2007 Jan 31. The goal of this short review is to consider the interrelated phenomena of phenotypic variation and genetic constraint with respect to plant diversity. The unique aspects of plants, including sessile habit, modular growth and diverse developmental programs expressed at the phytomer level, merit a specific examination of the genetic basis of their phenotypic variation, and how they experience and escape genetic constraint. Numerous QTL studies with wild and domesticated plants reveal that most phenotypic traits are polygenic but vary in the number and effect of the loci contributing, from a few loci of large effects to many with small effects. Further, somatic mutations, developmental plasticity and epigenetic variation, especially gene methylation, can contribute to increases in phenotypic variation. The flip side of these processes, genetic constraint, can similarly be the result of many factors, including pleiotropy, canalization and genetic redundancy. Genetic constraint is not only a mechanism to prevent change, however, it can also serve to direct evolution along certain paths. Ultimately, genetic constraint often comes full circle and is released through events such as hybridization, genome duplication and epigenetic remodeling. We are just beginning to understand how these processes can operate simultaneously during the evolution of ecologically important traits in plants. Variation and constraint in plant evolution and development
Finding a match-How do homologous sequences get together for recombination Barzel A, Kupiec M. Finding a match: how do homologous sequences get together for recombination? Nat Rev Genet. 2008 Jan; 9 (1): 27-37. Decades of research into homologous recombination have unravelled many of the details concerning the transfer of information between two homologous sequences. By contrast, the processes by which the interacting molecules initially colocalize are largely unknown. How can two homologous needles find each other in the genomic haystack? Is homologous pairing the result of a damage-induced homology search, or is it an enduring and general feature of the genomic architecture that facilitates homologous recombination whenever and wherever damage occurs? This Review presents the homologous-pairing enigma, delineates our current understanding of the process and offers guidelines for future research. Recent advances in plant recombination Li J, Hsia AP, Schnable PS. Recent advances in plant recombination. Curr Opin Plant Biol. 2007 Apr; 10 (2): 131-5. Epub 2007 Feb 8. Recombination is an essential cellular process and a source of genetic diversity. Recent studies have demonstrated the effects of various factors (e.g. DNA sequence similarity and activation of transposons) on rates of recombination and the distribution of recombination breakpoints in plants. These studies have also provided detailed characterizations of interchromatid and interhomolog recombination events. New approaches offer the promise of achieving the long-awaited goal of gene targeting in plants. Plant genome modification by homologous recombination Hanin M, Paszkowski J. Plant genome modification by homologous recombination. Curr Opin Plant Biol. 2003 Apr; 6 (2): 157-62. The mechanisms and frequencies of various types of homologous recombination (HR) have been studied in plants for several years. However, the application of techniques involving HR for precise genome modification is still not routine. The low frequency of HR remains the major obstacle but recent progress in gene targeting in Arabidopsis and rice, as well as accumulating knowledge on the regulation of recombination levels, is an encouraging sign of the further development of HR-based approaches for genome engineering in plants. Recombination-an underappreciated factor in evolution of plant genomes Gaut BS, Wright SI, Rizzon C, Dvorak J, Anderson LK. Recombination: an underappreciated factor in the evolution of plant genomes. Nat Rev Genet. 2007 Jan; 8 (1): 77-84. Our knowledge of recombination rates and patterns in plants is far from being comprehensive. However, compelling evidence indicates a central role for recombination, through its influences on mutation and selection, in the evolution of plant genomes. Furthermore, recombination seems to be generally higher and more variable in plants than in animals, which could be one of the primary reasons for differences in genome lability between these two kingdoms. Much additional study of recombination in plants is needed to investigate these ideas further. Genetics: paramutable possibilities Soloway PD. Genetics: paramutable possibilities. Nature. 2006 May 25; 441 (7092): 413-4 Paramutation: an encounter leaving a lasting impression Stam M, Mittelsten Scheid O. Paramutation: an encounter leaving a lasting impression. Trends Plant Sci. 2005 Jun; 10 (6): 283-90. Paramutation is the result of heritable changes in gene expression that occur upon interaction between alleles. Whereas Mendelian rules, together with the concept of genetic transmission via the DNA sequence, can account for most inheritance in sexually propagating organisms, paramutation-like phenomena challenge the exclusiveness of Mendelian inheritance. Most paramutation-like phenomena have been observed in plants but there is increasing evidence for its occurrence in other organisms, including mammals. Our knowledge of the underlying mechanisms, which might involve RNA silencing, physical pairing of homologous chromosomal regions or both, is still limited. Here, we discuss the characteristics of different paramutation-like interactions in the light of arguments supporting each of these alternative mechanisms. Paramutation and transgene silencing: A common responsive to invasive DNA? Finding a match-How do homologous sequences get together for recombination Recent advances in plant recombination Plant genome modification by homologous recombination Recombination-an underappreciated factor in evolution of plant genomes Genetics-paramutable possibilities Paramutation-an encounter leaving a lasting impression Paramutation and transgene silencing-A common responsive to invasive DNA From centiMorgans to base-pairs: homologous recombination in plants From centiMorgans to base-pairs: homologous recombination in plants
The chromosome number in humans Gartler SM. The chromosome number in humans: a brief history. Nat Rev Genet. 2006 Aug; 7 (8): 655-60 Following the rediscovery of Mendel's work in 1900, the field of genetics advanced rapidly. Human genetics, however, lagged behind; this was especially noticeable in cytogenetics, which was already a mature discipline in experimental forms in the 1950s. We did not know the correct human chromosome number in 1955, let alone were we able to detect a chromosomal abnormality. In 1956 a discovery was reported that markedly altered human cytogenetics and genetics. The following is an analysis of that discovery. The chromosome number in humans B chromosomes in plants: escapees from the A chromosome genome? Jones N, Houben A. B chromosomes in plants: escapees from the A chromosome genome? Trends Plant Sci. 2003 Sep; 8 (9): 417-23 B chromosomes are dispensable elements that do not recombine with the A chromosomes of the regular complement and that follow their own evolutionary track. In some cases, they are known to be nuclear parasites with autonomous modes of inheritance, exploiting drive to ensure their survival in populations. Their selfishness brings them into conflict with their host nuclear genome and generates a host-parasite relationship, with anti-B-chromosome genes working to ameliorate the worst of their excesses in depriving their hosts of genetic resources. Molecular studies are homing in on their sequence organization to give us an insight into the origin and evolution of these enigmatic chromosomes, which are, with rare exceptions, without active genes. B chromosomes in plants The advantages and disadvantages of being polyploidy Comai L. The advantages and disadvantages of being polyploid. Nat Rev Genet. 2005 Nov; 6 (11): 836-46 Polyploids - organisms that have multiple sets of chromosomes - are common in certain plant and animal taxa, and can be surprisingly stable. The evidence that has emerged from genome analyses also indicates that many other eukaryotic genomes have a polyploid ancestry, suggesting that both humans and most other eukaryotes have either benefited from or endured polyploidy. Studies of polyploids soon after their formation have revealed genetic and epigenetic interactions between redundant genes. These interactions can be related to the phenotypes and evolutionary fates of polyploids. Here, I consider the advantages and challenges of polyploidy, and its evolutionary potential. The advantages and disadvantages of being polyploidy Breaking down taxonomic barriers in polyploidy research Mable BK. Breaking down taxonomic barriers in polyploidy research. Trends Plant Sci. 2003 Dec; 8 (12): 582-90 Polyploidy is important in the evolutionary history of plants, and it has played a crucial role in shaping the genome structures of all eukaryotes. New and rapidly improving techniques in genomics, cytogenetics and molecular ecology have resulted in a dramatic increase in publications about duplicate genes, genome rearrangements and detection of ancient duplication events. Similarly, research associated with the origins of polyploidy, its persistence in natural populations and the resulting ecological consequences is receiving more attention. Although polyploidy research has been conducted using both animal and plant systems, inferences based on cross-disciplinary comparisons have been rare. Here, I review recent developments in the field in both plants and animals, emphasizing the benefits of communication between the two groups. Breaking down taxonomic barriers in polyploidy research Polyploidy and genome evolution in plants Adams KL, Wendel JF. Polyploidy and genome evolution in plants. Curr Opin Plant Biol. 2005 Apr; 8 (2): 135-41 Genome doubling (polyploidy) has been and continues to be a pervasive force in plant evolution. Modern plant genomes harbor evidence of multiple rounds of past polyploidization events, often followed by massive silencing and elimination of duplicated genes. Recent studies have refined our inferences of the number and timing of polyploidy events and the impact of these events on genome structure. Many polyploids experience extensive and rapid genomic alterations, some arising with the onset of polyploidy. Survivorship of duplicated genes are differential across gene classes, with some duplicate genes more prone to retention than others. Recent theory is now supported by evidence showing that genes that are retained in duplicate typically diversify in function or undergo subfunctionalization. Polyploidy has extensive effects on gene expression, with gene silencing accompanying polyploid formation and continuing over evolutionary time. Polyploidy and genome evolution in plants
Telomeres, telomeraes, and plant development Shippen DE, McKnight TD. Telomeres, telomeraes, and plant development. Trends Plant Sci. 1998, 3 (4): 126-130 Telomeres, telomeraes, and plant development The multifunctional nucleolus Boisvert FM, van Koningsbruggen S, Navascus J, Lamond AI. The multifunctional nucleolus. Nat Rev Mol Cell Biol. 2007 Jul; 8 (7): 574-85 The nucleolus is a distinct subnuclear compartment that was first observed more than 200 years ago. Nucleoli assemble around the tandemly repeated ribosomal DNA gene clusters and 28S, 18S and 5.8S ribosomal RNAs (rRNAs) are transcribed as a single precursor, which is processed and assembled with the 5S rRNA into ribosome subunits. Although the nucleolus is primarily associated with ribosome biogenesis, several lines of evidence now show that it has additional functions. Some of these functions, such as regulation of mitosis, cell-cycle progression and proliferation, many forms of stress response and biogenesis of multiple ribonucleoprotein particles, will be discussed, as will the relation of the nucleolus to human diseases. The multifunctional nucleolus What is new in the nucleolus?: workshop on the nucleolus: new perspectives. Matthews DA, Olson MO. What is new in the nucleolus?: workshop on the nucleolus: new perspectives. EMBO Rep. 2006 Sep; 7 (9): 870-3. Epub 2006 Aug 18 What is new in the nucleolus
A molecular view of plant centromeres Jiang J , Birchler JA , Parrott WA , Dawe RK. A molecular view of plant centromeres. Trends Plant Sci. 2003 Dec; 8 (12): 570-5 Although plants were the organisms of choice in several classical centromere studies, molecular and biochemical studies of plant centromeres have lagged behind those in model animal species. However, in the past several years, several centromeric repetitive DNA elements have been isolated in plant species and their roles in centromere function have been demonstrated. Most significantly, a Ty3/gypsy class of centromere-specific retrotransposons, the CR family, was discovered in the grass species. The CR elements are highly enriched in chromatin domains associated with CENH3, the centromere-specific histone H3 variant. CR elements as well as their flanking centromeric satellite DNA are actively transcribed in maize. These data suggest that the deposition of centromeric histones might be a transcription-coupled event. A molecular view of plant centromeres DNA and proteins of plant centromeres Houben A, Schubert I. DNA and proteins of plant centromeres. Curr Opin Plant Biol. 2003 Dec; 6 (6): 554-60 In plants, as in all eukaryotes, centromeres are chromatin domains that govern the transmission of nuclear chromosomes to the next generation of cells/individuals. The DNA composition and sequence organization of centromeres has recently been elucidated for a few plant species. Although there is little sequence conservation among centromeres, they usually contain tandem repeats and retroelements. The occurrence of neocentromeres reinforces the idea that the positions of centromeres are determined epigenetically. In contrast to centromeric DNA, structural and transient kinetochoric proteins are highly conserved among eukaryotes. Candidate sequences have been identified for a dozen putative kinetochore protein homologues, and some have been localized to plant centromeres. The kinetochore protein CENH3, which substitutes histone H3 within centromeric nucleosomes, co-immunoprecipitates preferentially with centromeric sequences. The mechanism(s) of centromere assembly and the functional implication of (peri-)centromeric modifications of chromatin remain to be elucidated. DNA and proteins of plant centromeres The rapidly evolving field of plant centromeres Hall AE, Keith KC, Hall SE, Copenhaver GP, Preuss D. The rapidly evolving field of plant centromeres. Curr Opin Plant Biol. 2004 Apr;7(2):108-14 Meiotic and mitotic chromosome segregation are highly conserved in eukaryotic organisms, yet centromeres--the chromosomal sites that mediate segregation--evolve extremely rapidly. Plant centromeres have DNA elements that are shared across species, yet they diverge rapidly through large- and small-scale changes. Over evolutionary time-scales, centromeres migrate to non-centromeric regions and, in plants, heterochromatic knobs can acquire centromere activity. Discerning the functional significance of these changes will require comparative analyses of closely related species. Combined with functional assays, continued efforts in plant genomics will uncover key DNA elements that allow centromeres to retain their role in chromosome segregation while allowing rapid evolution. The rapidly evolving field of plant centromeres Centrosome biogenesis and function: centrosomics brings new understanding Bettencourt-Dias M, Glover DM. Centrosome biogenesis and function: centrosomics brings new understanding. Nat Rev Mol Cell Biol. 2007 Jun; 8 (6): 451-63. Centrosomes, which were first described in the late 19th century, are found in most animal cells and undergo duplication once every cell cycle so that their number remains stable, like the genetic material of a cell. However, their function and regulation have remained elusive and controversial. Only recently has some understanding of these fundamental aspects of centrosome function and biogenesis been gained through the concerted application of genomics and proteomics, which we term 'centrosomics'. The identification of new molecules has highlighted the evolutionary conservation of centrosome function and provided a conceptual framework for understanding centrosome behaviour and how it can go awry in human disease. Centrosome biogenesis and function-centrosomics brings new understanding
The organization and function of chromosomes Baird DM, Farr CJ. The organization and function of chromosomes. EMBO Rep. 2006 Apr; 7 (4): 372-6. Epub 2006 Mar 17 The organization and function of chromosomes Genomes, genes and junk, the large scale organization of chromosomes Schmidt T, Heslop-Harrison JS. Genomes, genes and junk, the large scale organization of chromosomes. Trends Plant Sci. 1998 May; 3 (5): 195-9 Genomes, genes and junk, the large scale organization of chromosomes Heterochromatin revisited Grewal SI, Jia S. Heterochromatin revisited. Nat Rev Genet. 2007 Jan; 8 (1): 35-46 The formation of heterochromatin, which requires methylation of histone H3 at lysine 9 and the subsequent recruitment of chromodomain proteins such as heterochromatin protein HP1, serves as a model for the role of histone modifications and chromatin assembly in epigenetic control of the genome. Recent studies in Schizosaccharomyces pombe indicate that heterochromatin serves as a dynamic platform to recruit and spread a myriad of regulatory proteins across extended domains to control various chromosomal processes, including transcription, chromosome segregation and long-range chromatin interactions. Heterochromatin revisited Plant chromosomes from end to end: telomeres, heterochromatin and centromeres Lamb JC , Yu W , Han F , Birchler JA . Plant chromosomes from end to end: telomeres, heterochromatin and centromeres. Curr Opin Plant Biol. 2007 Apr; 10 (2): 116-22. Epub 2007 Feb 8. Recent evidence indicates that heterochromatin in plants is composed of heterogeneous sequences, which are usually composed of transposable elements or tandem repeat arrays. These arrays are associated with chromatin modifications that produce a closed configuration that limits transcription. Centromere sequences in plants are usually composed of tandem repeat arrays that are homogenized across the genome. Analysis of such arrays in closely related taxa suggests a rapid turnover of the repeat unit that is typical of a particular species. In addition, two lines of evidence for an epigenetic component of centromere specification have been reported, namely an example of a neocentromere formed over sequences without the typical repeat array and examples of centromere inactivation. Although the telomere repeat unit is quite prevalent in the plant kingdom, unusual repeats have been found in some families. Recently, it was demonstrated that the introduction of telomere sequences into plants cells causes truncation of the chromosomes, and that this technique can be used to produce artificial chromosome platforms. Plant chromosomes from end to end Planning for remodeling: nuclear architecture, chromotin and chromosomes Heslop-Harrison JS. Planning for remodelling: nuclear architecture, chromatin and chromosomes. Trends Plant Sci. 2003 May; 8 (5): 195-7 DNA sequences occupy three-dimensional positions and their architecture is related to gene expression, gene-protein interactions and epigenetic processes. The recent analysis of chromosome 4 in Arabidopsis interphase nuclei reveals that gene-rich, undermethylated DNA is composed of active loops of 200 to 2000 kb associated with acetylated histones, providing a well-defined model system to study chromatin in its nuclear context. Planning for remodeling-nuclear architecture, chromotin and chromosomes Advances in plant chromosome identification and cytogenetic techniques Kato A, Vega JM, Han F, Lamb JC, Birchler JA. Advances in plant chromosome identification and cytogenetic techniques. Curr Opin Plant Biol. 2005 Apr; 8 (2):148-54. Recent developments that improve our ability to distinguish slightly diverged genomes from each other, as well as to distinguish each of the nonhomologous chromosomes within a genome, add a new dimension to the study of plant genomics. Differences in repetitive sequences among different species have been used to develop multicolor fluorescent in situ hybridization techniques that can define the components of allopolyploids in detail and reveal introgression between species. Bacterial artificial chromosome probes and repetitive sequence arrays have been used to distinguish each of the nonhomologous somatic chromosomes within a species. Such karyotype analysis opens new avenues for the study of chromosomal variation and behavior, as well as for the localization of individual genes and transgenes to genomic position. Advances in plant chromosome identification and cytogenetic techniques Reinterpreting pericentrimeric Heterochromatin Topp CN, Dawe RK. Reinterpreting pericentromeric heterochromatin. Curr Opin Plant Biol. 2006 Dec; 9 (6): 647-53. Epub 2006 Oct 2 In fission yeast, pericentromeric heterochromatin is directly responsible for the sister chromatid cohesion that assures accurate chromosome segregation. In plants, however, heterochromatin and chromosome segregation appear to be largely unrelated: chromosome transmission is impaired by mutations in cohesion but not by mutations that affect heterochromatin formation. We argue that the formation of pericentromeric heterochromatin is primarily a response to constraints on chromosome mechanics that disfavor the transmission of recombination events in pericentromeric regions. This effect allows pericentromeres to expand to enormous sizes by the accumulation of transposons and through large-scale insertions and inversions. Although sister chromatid cohesion is spatially limited to pericentromeric regions at mitosis and meiosis II, the cohesive domains appear to be defined independently of heterochromatin. The available data from plants suggest that sister chromatid cohesion is marked by histone phosphorylation and mediated by Aurora kinases. Reinterpreting pericentrimeric Heterochromatin
生物学和遗传学的革命 单核苷酸多态性（ SNP ）取代基因（ gene ）成为遗传单位 《新闻周刊》发表文章《奇迹之年》（ The Year of Miracles ）指出，对人类自身进行探索的基因研究成为全球的科研热点，正是基因研究的奇迹之年 2007 年，有关致病基因的一系列新发现颠覆了人类对于基因和遗传的传统认知，单核苷酸多态性（ SNP ）取代基因（ gene ）成为遗传单位。 The Year of Miracles By Lee Silver | NEWSWEEK ， Oct 15, 2007 Issue Variations in these particular letterscalled snips, or SNPs, for single nucleotide polymorphismshave replaced genes as the unit of heredity. The year 1905 was an annus mirabilis, or miracle yearA rare historical moment in which key flashes of insight suddenly made the field of physics take off in new directions. That was the year Albert Einstein presented four papers that turned the conventional wisdom about how the universe works, from the infinitesimal realm of atoms to the vast reaches of the cosmos, upside down. During the next several decades, Einstein and a handful of other brilliant physicists went on to shape the 20th century and lay the foundation for all its technological accomplishments. A century later, the year 2007 is shaping up to be another annus mirabilis. This time biology is the field in transition, and the ideas being shattered are old notions of genes and inheritance. Ever since 1900, when Gregor Mendel's work on peas and inheritance was rediscovered, scientists have regarded the gene as the fundamental unit of heredity (just as the atom was regarded as the bedrock of pre-Einsteinian physics). Crick and Watson's discovery of the DNA double helix as the carrier of hereditary information did little to disturb the status quo. In recent months, however, a perfect storm of new technology and research has blown apart 20th-century dogma. The notion of the Mendelian gene as a unit of heredity, scientists now realize, is a fiction. What's taking its place? Many scientists now believe that heredity is the result of an incredibly complex interplay among the basic components of the genome, scattered among many different genes and even the vast stretches of junk DNA once thought to serve no purpose. Biology has been building up to this insight for years, but some big puzzle pieces have now fallen into place. Once scientists abandoned their preconceived notions of genes and looked instead at individual DNA letters in the genome the four bases A, C, T and Gthey immediately began to see cause-and-effect connections to myriad diseases and human traits. The result of this seemingly modest conceptual breakthrough has been a torrent of new discoveries. In five months, from April through August, geneticists at the Harvard/MIT Broad Institute, founded by Eric Lander; at deCODE Genetics in Iceland , founded by Kari Stefansson, and several other institutions have published papers suggesting that the key to a deeper understanding of the human genome may finally be in hand. These scientists have identified specific alterations in the sequence of DNA that play causative roles in a broad range of common diseases, including type 1 and type 2 diabetes; schizophrenia; bipolar disorder; glaucoma; inflammatory bowel disease; rheumatoid arthritis; hypertension; restless legs syndrome; susceptibility to gallstone formation; lupus; multiple sclerosis; coronary heart disease; colorectal, prostate and breast cancer, and the pace at which HIV infection causes full-blown AIDS. Unlike so many previous disease gene discoveries, these findings are being replicated and validated. The race to discover disease-linked genes reaches fever pitch, declared the leading British science journal, Nature. Its American counterparts at Science chimed in: After years of chasing false leads, gene hunters feel that they have finally cornered their prey. They are experiencing a rush this spring as they find, time after time, that a new strategy is enabling them to identify genetic variations that likely lie behind common diseases. That the world's top two scientific journals still use the old language of genes to describe these discoveries shows how new the new thinking really is. These findings are just a prelude to what's shaping up as a true conceptual and technological revolution. Just as physics shocked the world in the 20th century, it is now clear that the life sciences will shake up the world in the 21st. In a handful of years, your doctor may be able to run a computer analysis of your personal genome to get a detailed profile of your health prospects. This goes well beyond merely making predictions. A new technology called RNA interference may also allow doctors to control how your DNA is expressed, helping you circumvent potential health risks. Many common diseases that have preyed on humans for eonsdevastating neurological conditions such as Alzheimer's, Parkinson's, cancer and heart diseasecould be eradicated. If this sounds outrageously optimistic, so did the promise of eliminating smallpox and polio to previous generations. Why is all this happening now? What has changed between this year and last? To answer these questions, we need to trace the story of how mainstream biomedical scientists tried to link the cause of diseases to single genes and, despite early success, hit a brick wall. Meanwhile, a handful of renegade scientists, pursuing their own pet projects, happened to develop exactly the intellectual tools needed to break through that wall. These biologists are now the leaders of the new revolution in biomedical science. The seeds of our new understanding were first sown in the 1960s, when molecular biologists figured out how genetic information is organized, regulated and reproduced inside single-cell bacteria. In bacteria, a gene is a discrete segment of DNA that contains the code that tells the cell how to make a particular type of protein. Bacterial genes are arranged along a single DNA molecule, one after the other, with only tiny gaps in between. Since all organisms have DNA and work by essentially the same biochemistry, scientists assumed that a human genome would look like a larger version of a bacterium's. Clues that something was amiss came quickly with the development of DNA-sequencing methods in the 1970s. The first surprising result was that genes accounted for only 2 percent of the human genomethe rest of the DNA didn't seem to have any purpose at all. Biologists Phillip Sharp and Richard Roberts made things worse with a discovery that won them a Nobel Prize in 1993. If the gene were the basic unit of heredity, the DNA required to make any particular protein should be contained in its corresponding gene. But Sharp and Roberts found that DNA that codes for individual proteins is often split and scattered throughout the genome. Scientists could ignore these signs largely because they seemed to be making progress. By combining new DNA-sequencing tools with studies of inherited diseases in large families, medical geneticists identified the genetic culprits responsible for cystic fibrosis, Huntington's disease, Duchenne muscular dystrophy and a host of other diseases. Each of these all or none diseases is caused by a mutation in a single protein-coding region of the DNA. Few diseases, unfortunately, work so neatly. In particular, the search for genetic bases of common diseases that affect large numbers of aging people came up empty. During this lull, a visionary physician-scientist named Leroy Hood, now at the Institute for Systems Biology in Seattle , was growing impatient. Genetics, he recognized, was still a cottage industry of government-funded university professors, who each directed a small group of students and technicians to study an isolated gene. At the pace research was progressing, it would have required 100,000 worker-years of concerted effort to decipher just one complete human genome. Hood thought it was absurd that genetic scientists spent nearly all their lab time performing tedious and repetitive mechanical and chemical procedures. At the same time, he grasped the far-reaching implications of a fundamental fact: while even the simplest organism is immensely complicated, the primary structures of its most complicated partsDNA and proteinsare very simple. The alphabet of DNA contains only the four chemical letters (or bases) A, C, G and T, and proteins are made from just 21 amino acids. Hood saw that this simplicity would make it possible for robots and computers to read and write DNA and proteins more quickly, accurately and cheaply than human beings. The rest of the biomedical community refused to believe that robots could analyze something as complex as a living system. And in any case, no practicing geneticist had the capacity to design such machines. Unable to obtain government grants, Hood secured private funding to bring together dozens of scientists, engineers and computer programmers (far larger and more diverse than any other genetics team). They proceeded to invent the first generation of molecular-biology machines. Two read and recorded information from DNA and proteins respectively (a process known as sequencing), and two others worked backward, converting digital electronic information into newly written sequences of DNA or protein. Hood completely transformed the biomedical enterprise. DNA-writing machines give genetic engineers an unlimited capacity to create novel genes that can be studied in test tubes or added to the genomes of living organisms. And protein-writing and -reading machines provided drug firms with the ability to create a new generation of protein-based drugs. The DNA-reading machines suddenly made it conceivable to crack the 3 billion-base sequence of an entire human genome. In 1990 the U.S. government embarked on a 15-year, $3 billion project to do just that. Eight years later, however, the projectparceled out to many U.S. scientistswas still less than 10 percent complete. Now it was biotech entrepreneur Craig Venter who was frustrated. Convinced that government-funded workers were the problem rather than the solution, Venter enlisted private funding of $200 million to build an enormous lab filled with hundreds of automated machines, working 24/7, overseen by a handful of technicians. Within three years, the first reading of a human genome was essentially complete. Armed with data from the genome project, scientists figured they'd surely be able to crack the really hard diseases, like cancer and heart disease. But a funny thing happened when they began to look closely at this vast storehouse of genetic information. Geneticists Andrew Fire and Craig Melo galvanized the field by discovering a key mechanism that had been completely overlookedthe cellular process of RNA interference. (They shared a Nobel Prize in 2006 for the work.) Finding evidence of extraterrestrial life couldn't have come as a bigger shock. Geneticists had taken for granted that the machinery of cells involved genes directing the production of proteins, and proteins doing the work of the cell. Here was a process that didn't involve proteins at all. Instead, tens of thousands of hitherto mysterious regions of the human genomepart of the so-called junk DNAdirected the production of specific molecules called microRNAs (consisting of bits of RNA, a well-known component of cells). These microRNAs then oversaw a whole new process, called RNA interference (RNAi), that served to modulate the expression of DNA. The good news was that RNAi could open up a whole new approach to biomedical therapy (more on that later). But RNAi also made it clear that the fundamental unit of heredity and genetic function is not the gene but the position of each individual DNA letter. To make it all harder to fathom, each bit of DNA is susceptible to mutation and variation among individuals. Of the 3 billion DNA bases in the human genome, geneticists identified about one tenth of one percent (millions) that differ from one person to another. Variations in these particular letterscalled snips, or SNPs, for single nucleotide polymorphismshave replaced genes as the unit of heredity. Many scientists responded to this devastating realization by going into a funk. It will be difficult, if not impossible, to find the genes involved or develop useful and reliable predictive tests for them, Dr. Neil Holtzman, director of genetics and public policy at Johns Hopkins University , said in 2001. Fortunately, another visionary scientist, Kari Stefansson of Iceland , was already blazing a trail out of this thicket. If the genome was far more complex than scientists had thought, they would need to test for many more variables, and to do that they would need more test subjects. To find the cause of diseases would now require the participation of very large groups of genetically related people. Like Hood and Venter, Stefansson was originally motivated by frustration with the pace of research. In the United States , where most of the disease-gene-discovery projects were being conducted, most people cannot trace their ancestors back more than a few generations, and the largest families consist of a few hundred living subjects at most. Subject panels of this size failed to provide sufficient data to identify the genetic bases for complicated and variable common diseases. Stefansson decided to solve this problem by taking aim at the largest well-documented extended family that he knewhis own. Nearly all the 300,000 citizens of Iceland can trace their ancestors back, through detailed, public genealogical records, to the Vikings who settled this desolate European island more than 1,000 years ago. Stefansson gave up his faculty position at Harvard Medical School to return to Iceland , where he founded the company deCODE Genetics in 1996. He persuaded the Icelandic government to provide deCODE with exclusive access to the health records of its citizens in return for bringing investment capital and high-tech jobs to the capital, Reykjavik . So far, more than 100,000 Icelandic volunteers have donated their DNA to deCODE. Stefansson's project was roundly criticized by international bioethicists and other geneticists for violating the privacy of Icelanders (even though 90 percent of the population approved). Nevertheless, he persevered, placing the genealogy of the entire nation on a computer database, together with the health and DNA records of still-living individuals. The power of large numbers was soon apparent. In a study of obesity, he directed his software to look for SNPs associated with subsets of the population who were either extremely overweight or very thin. Within just a few hours, it began finding evidence that variations among particular DNA letters indeed played a causative role, confirming SNPs as the new unit of inheritance. As of September, deCODE has made progress in identifying SNPs that may play a role in 28 common diseases, including glaucoma, schizophrenia, diabetes, heart disease, prostate cancer, hypertension and stroke. In some cases, such as glaucoma and prostate cancer, deCODE's findings could lead to diagnostic tests for identifying people at risk of developing the disease. In other instances, such as schizophrenia, links to particular proteins have led to insight about the cause of the disease, which could lead to therapies. Buoyed by Stefansson's success, other geneticists were eager to perform large-scale family studies, yet few had similar access to ancient genealogical records. But serendipity would deliver an epiphany: it's possible to study the entire human population as a single extended family, provided scientists collect enormous amounts of data. Eric Lander, an MIT professor and the intellectual leader of the U.S. government effort to sequence the first human genome, realized scaling up would require a new approach. In 2004, Lander persuaded MIT and Harvard to combine their enormous resources toward the creation of the Broad Institute. Backed by $200 million from billionaire philanthropists Eli and Edythe Broad, the institute is driving the development of ever more advanced genetic technologies. One technology, based on computer-chip fabrication, can identify DNA base letters present at 500,000 SNPs in the genomes of 40,000 or more people. Think of this as a spreadsheet with 500,000 columns (each representing a specific SNP) and 40,000 rows (one for each person). To hunt for a genetic basis for, say, bipolar disease, the computer searches rows of people who have the disorder, checking column by column for an unusually high frequency of particular letters in comparison with people without the disease. As it turns out, a collaboration of American and German researchers has done this workand found that variations of DNA letters in 20 different positions are influential in bipolar disease. Incredibly, most disease-causing variants are the most common ones present in the human population: the strongest-acting one, for instance, exists in 80 percent of people without bipolar disease and 85 percent of people with the disease. The implication is that these variants are beneficial in some way, and cause problems only when their number exceeds a threshold. To make sense of this complexity, scientists would like ultimately to build a vast international database that contains the complete sequence of DNA bases in the genomes of hundreds of millions of people. Ideally, such a database would be available for analysis by all biomedical researchers and would provide the foundation for understanding the genetic components of all human traits. That sounds like a lot of datathink of a spreadsheet with 3 billion columns and 100 million rowsbut computing power is getting cheaper by the year. Within a decade, the cost of obtaining a sequence of all 3 billion DNA letters in an individual's genome will drop from $2 million now to $1,000. It will be a routine part of a person's health record, enabling physicians to prescribe genome-specific preventions and treatments. The discovery of RNAi, meanwhile, suggests a completely new personalized form of disease therapy. Whereas drugs act on proteins, RNAi therapy would act on the expression of DNA itself, potentially preventing or reversing diseases such as Alzheimer's, Parkinson's, Huntington's, bipolar disorder, schizophrenia and others. Old-school pharmaceutical firms have taken notice. The largest ones are betting heavily on the gene-targeted RNAi therapeutic approach to fill product pipelines, as the discovery of traditional chemical drugs becomes more elusive. Novartis and Roche have both signed nonexclusive licensing deals with the biotech firm Alnylam (founded by Phillip Sharp) for new therapeutic techniques that are valued at up to $700 million and $1 billion respectively; Merck paid $1.1 billion to buy another biotech company outright, solely to obtain its contested portfolio of RNAi intellectual property, and the London-based drug firm AstraZeneca has a $405 million licensing deal with Alnylam's competitor Silence Therapeutics. The explosion of genetic discoveries shows no sign of letting up any time soon. New diseases are being added to the list every month, and biologists are rapidly parlaying gene- and SNP-disease links into a deeper understanding of how proteins and other molecules can misbehave to cause different medical problems in different people. And other scientists are working to advance the biology revolution (accompanying interviews). As a result of their efforts, many children born this year could very well be alive and healthy at the dawn of the next century, when they may look back in awe at the annus mirabilis of biomedical genetics in 2007. Silver is a professor of molecular biology at Princeton . He is the author of Challenging Nature. He has no financial ties to any biotech or drug firm. Silver is a professor of molecular biology at Princeton . He is the author of Challenging Nature. He has no financial ties to any biotech or drug firm. Newsweek, Inc.
How many genes are there in plants (... and why are they there)? Sterck L, Rombauts S, Vandepoele K, Rouz P, Van de Peer Y. How many genes are there in plants (... and why are they there)? Curr Opin Plant Biol. 2007 Apr; 10 ( 2 ): 199-203 . Epub 2007 Feb 7. Review. Annotation of the first few complete plant genomes has revealed that plants have many genes. For Arabidopsis, over 26,500 gene loci have been predicted, whereas for rice, the number adds up to 41,000. Recent analysis of the poplar genome suggests more than 45,000 genes, and partial sequence data from Medicago and Lotus also suggest that these plants contain more than 40,000 genes. Nevertheless, estimations suggest that ancestral angiosperms had no more than 12,000-14,000 genes. One explanation for the large increase in gene number during angiosperm evolution is gene duplication. It has been shown previously that the retention of duplicates following small- and large-scale duplication events in plants is substantial. Taking into account the function of genes that have been duplicated, we are now beginning to understand why many plant genes might have been retained, and how their retention might be linked to the typical lifestyle of plants. How many genes are there in plants Do plants have more genes than humans? Do plants have more genes than humans Do plants have more genes than humans? Yes, when it comes to ABC proteins. Do plants have more genes than humans
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