Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003, Barcelona, Spain.
Institute of Biotechnology and Biomedicine, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), 08193, Barcelona, Spain.
Nat Commun. 2020 Jul 3;11(1):3304. doi: 10.1038/s41467-020-17162-z.
A main assumption of molecular population genetics is that genomic mutation rate does not depend on sequence function. Challenging this assumption, a recent study has found a reduction in the mutation rate in exons compared to introns in somatic cells, ascribed to an enhanced exonic mismatch repair system activity. If this reduction happens also in the germline, it can compromise studies of population genomics, including the detection of selection when using introns as proxies for neutrality. Here we compile and analyze published germline de novo mutation data to test if the exonic mutation rate is also reduced in germ cells. After controlling for sampling bias in datasets with diseased probands and extended nucleotide context dependency, we find no reduction in the mutation rate in exons compared to introns in the germline. Therefore, there is no evidence that enhanced exonic mismatch repair activity determines the mutation rate in germline cells.
分子群体遗传学的一个主要假设是基因组突变率不依赖于序列功能。最近的一项研究对这一假设提出了挑战，该研究发现体细胞中的exon 突变率相对于 intron 降低，这归因于增强的exon 错配修复系统活性。如果这种降低也发生在生殖细胞中，它可能会影响群体基因组学的研究，包括使用 intron 作为中性替代物来检测选择。在这里，我们编译和分析已发表的生殖系从头突变数据，以测试生殖细胞中的exon 突变率是否也降低。在控制了患病先证者数据集和扩展核苷酸上下文依赖性中的采样偏差后，我们没有发现生殖系中的exon 突变率相对于 intron 降低。因此，没有证据表明增强的exon 错配修复活性决定了生殖细胞中的突变率。
