Decreased recent adaptation at human mendelian disease genes as a possible consequence of interference between advantageous and deleterious variants.
Decreased recent adaptation at human mendelian disease genes as a possible consequence of interference between advantageous and deleterious variants.
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DOI：
10.7554/elife.69026
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发表时间：
2021-10-12
期刊：
影响因子：
7.7
通讯作者：
Enard D
中科院分区：
文献类型：
--
作者：
Di C;Murga Moreno J;Salazar-Tortosa DF;Lauterbur ME;Enard D
基因组测序的进步提高了我们对人类疾病遗传基础的理解，成千上万的人类基因与不同的疾病有关。最近疾病基因的基因组适应还没有很好地表征。在这里，我们比较了来自1000个基因组计划的不同人群中孟德尔、非传染性疾病基因和非疾病基因之间的选择性扫描形式的强近期适应率。我们发现，与非疾病基因相比，孟德尔病基因经历的选择性扫描要少得多，尤其是在非洲。进一步调查疾病基因扫描缺陷的可能原因，我们发现这种缺陷在低重组率和大量相关疾病变异的疾病基因中非常强烈，但在高重组率或低相关疾病变异的疾病基因中几乎不存在。由于分离性隐性有害变异能够干扰适应性变异，这些观察结果强烈表明，疾病基因上存在干扰性隐性有害变异，减缓了适应性。这些结果表明，疾病基因有一种短暂的不能像基因组其他部分一样快速适应的现象。
Advances in genome sequencing have improved our understanding of the genetic basis of human diseases, and thousands of human genes have been associated with different diseases. Recent genomic adaptation at disease genes has not been well characterized. Here, we compare the rate of strong recent adaptation in the form of selective sweeps between mendelian, non-infectious disease genes and non-disease genes across distinct human populations from the 1000 Genomes Project. We find that mendelian disease genes have experienced far less selective sweeps compared to non-disease genes especially in Africa. Investigating further the possible causes of the sweep deficit at disease genes, we find that this deficit is very strong at disease genes with both low recombination rates and with high numbers of associated disease variants, but is almost non-existent at disease genes with higher recombination rates or lower numbers of associated disease variants. Because segregating recessive deleterious variants have the ability to interfere with adaptive ones, these observations strongly suggest that adaptation has been slowed down by the presence of interfering recessive deleterious variants at disease genes. These results suggest that disease genes suffer from a transient inability to adapt as fast as the rest of the genome.
影响因子：
3.7
作者：
Eyre-Walker YC;Eyre-Walker A
通讯作者：
Eyre-Walker A