美国华盛顿大学医学院的Evan E. Eichler团队取得一项新成果。他们研究发现了反复倒位翻转和类人猿基因组进化。2020年6月15日出版的《自然-遗传学》杂志发表了这项成果。
通过使用单细胞DNA模板链和长片段测序，他们将以前报道的倒位的数目增加了六倍（n = 1,069）。他们发现，根据其大小和复制量，X染色体的倒位最富集（2.5倍）。在大（> 100 千碱基（kb））倒位的断裂点附近存在过量的差异表达的灵长类动物基因，但较小的却没有。他们表明，当出现类人猿谱系特定的复制时，与它们的祖先位置相比，它们优先（大约75％）以倒位方向出现。
他们构建单个染色体的兆碱基对规模单倍型，并确定23个基因组区域，这些区域在1500万年中已在直接状态和反向状态之间反复切换。直接定向最常见的是人类多态性的派生状态，其倾向于与神经发育疾病相关的复发性拷贝数变异。
研究人员表示，倒位在疾病和进化中起着重要作用，但由于其断点映射到大的重复序列而难以表征。
附：英文原文
Title: Recurrent inversion toggling and great ape genome evolution
Author: David Porubsky, Ashley D. Sanders, Wolfram Hps, PingHsun Hsieh, Arvis Sulovari, Ruiyang Li, Ludovica Mercuri, Melanie Sorensen, Shwetha C. Murali, David Gordon, Stuart Cantsilieris, Alex A. Pollen, Mario Ventura, Francesca Antonacci, Tobias Marschall, Jan O. Korbel, Evan E. Eichler
Issue&Volume: 2020-06-15
Abstract: Inversions play an important role in disease and evolution but are difficult to characterize because their breakpoints map to large repeats. We increased by sixfold the number (n=1,069) of previously reported great ape inversions by using single-cell DNA template strand and long-read sequencing. We find that the X chromosome is most enriched (2.5-fold) for inversions, on the basis of its size and duplication content. There is an excess of differentially expressed primate genes near the breakpoints of large (>100kilobases (kb)) inversions but not smaller events. We show that when great ape lineage-specific duplications emerge, they preferentially (approximately 75%) occur in an inverted orientation compared to that at their ancestral locus. We construct megabase-pair scale haplotypes for individual chromosomes and identify 23 genomic regions that have recurrently toggled between a direct and an inverted state over 15 million years. The direct orientation is most frequently the derived state for human polymorphisms that predispose to recurrent copy number variants associated with neurodevelopmental disease.
DOI: 10.1038/s41588-020-0646-x
Source: https://www.nature.com/articles/s41588-020-0646-x
Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex
本期文章：《自然—遗传学》：Online/在线发表
