Department of Biology, Stanford University, Stanford, CA 94305;
Department of Genetics, Stanford University, Stanford, CA 94305.
Proc Natl Acad Sci U S A. 2017 Nov 28;114(48):12779-12784. doi: 10.1073/pnas.1708151114. Epub 2017 Nov 14.
Gene conversion is the copying of a genetic sequence from a "donor" region to an "acceptor." In nonallelic gene conversion (NAGC), the donor and the acceptor are at distinct genetic loci. Despite the role NAGC plays in various genetic diseases and the concerted evolution of gene families, the parameters that govern NAGC are not well characterized. Here, we survey duplicate gene families and identify converted tracts in 46% of them. These conversions reflect a large GC bias of NAGC. We develop a sequence evolution model that leverages substantially more information in duplicate sequences than used by previous methods and use it to estimate the parameters that govern NAGC in humans: a mean converted tract length of 250 bp and a probability of [Formula: see text] per generation for a nucleotide to be converted (an order of magnitude higher than the point mutation rate). Despite this high baseline rate, we show that NAGC slows down as duplicate sequences diverge-until an eventual "escape" of the sequences from its influence. As a result, NAGC has a small average effect on the sequence divergence of duplicates. This work improves our understanding of the NAGC mechanism and the role that it plays in the evolution of gene duplicates.
基因转换是指从“供体”区域复制遗传序列到“受体”的过程。在非等位基因转换（NAGC）中，供体和受体位于不同的遗传基因座上。尽管 NAGC 在各种遗传疾病和基因家族的协同进化中发挥着作用，但控制 NAGC 的参数尚未得到很好的描述。在这里，我们调查了重复基因家族，并在其中 46%的家族中鉴定出了转化片段。这些转化反映了 NAGC 的较大 GC 偏倚。我们开发了一种序列进化模型，该模型利用了重复序列中的大量信息，比以前的方法利用的信息多得多，并使用该模型来估计控制人类 NAGC 的参数：每个核苷酸的平均转换片段长度为 250bp，每个世代的转换概率为[公式：见文本]（比点突变率高一个数量级）。尽管存在这种高基线率，但我们发现，随着重复序列的分化，NAGC 的速度会减慢——直到序列最终从其影响中“逃脱”。因此，NAGC 对重复序列的序列分化的平均影响较小。这项工作提高了我们对 NAGC 机制及其在基因重复进化中所扮演角色的理解。
