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同义突变揭示健康组织中全基因组的正向选择水平
2021-11-07 13:11

英国剑桥大学Jamie R. Blundell、Gladys Y. P. Poon等研究人员合作发现,同义突变揭示健康组织中全基因组的正向选择水平。2021年11月4日,《自然—遗传学》杂志在线发表了这项成果。

研究人员分析了来自健康血液和食道的同义突变的变体等位基因频率谱,用于量化缺失的正选择水平。在血液中,研究人员发现只有30%的乘客突变可以用驱动基因中的单核苷酸变异来解释,这表明基因组中其他地方的突变有高水平的正向选择。相比之下,食道中所有乘客突变的一半以上可以由两个驱动基因NOTCH1和TP53解释,表明其他地方的正选择很少。

据介绍,健康组织中正向选择下的基因改变对癌症风险有影响。然而,整个基因组的正向选择的总水平仍然未知。乘客突变会受到所有驱动突变的影响,无论其类型或在基因组中的位置如何。因此,乘客突变的总数可以用来估计驱动突变的总数,包括传统上被遗漏的癌症基因以外的未识别的驱动突变。

附:英文原文

Title: Synonymous mutations reveal genome-wide levels of positive selection in healthy tissues

Author: Poon, Gladys Y. P., Watson, Caroline J., Fisher, Daniel S., Blundell, Jamie R.

Issue&Volume: 2021-11-04

Abstract: Genetic alterations under positive selection in healthy tissues have implications for cancer risk. However, total levels of positive selection across the genome remain unknown. Passenger mutations are influenced by all driver mutations, regardless of type or location in the genome. Therefore, the total number of passengers can be used to estimate the total number of drivers—including unidentified drivers outside of cancer genes that are traditionally missed. Here we analyze the variant allele frequency spectrum of synonymous mutations from healthy blood and esophagus to quantify levels of missing positive selection. In blood, we find that only 30% of passengers can be explained by single-nucleotide variants in driver genes, suggesting high levels of positive selection for mutations elsewhere in the genome. In contrast, more than half of all passengers in the esophagus can be explained by just the two driver genes NOTCH1 and TP53, suggesting little positive selection elsewhere.

DOI: 10.1038/s41588-021-00957-1

Source: https://www.nature.com/articles/s41588-021-00957-1

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

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