Whitehead Institute, Cambridge, MA 02142, USA.
Howard Hughes Medical Institute, Whitehead Institute, Cambridge, MA 02142, USA.
G3 (Bethesda). 2021 Oct 19;11(11). doi: 10.1093/g3journal/jkab224.
Gene conversion is GC-biased across a wide range of taxa. Large palindromes on mammalian sex chromosomes undergo frequent gene conversion that maintains arm-to-arm sequence identity greater than 99%, which may increase their susceptibility to the effects of GC-biased gene conversion. Here, we demonstrate a striking history of GC-biased gene conversion in 12 palindromes conserved on the X chromosomes of human, chimpanzee, and rhesus macaque. Primate X-chromosome palindrome arms have significantly higher GC content than flanking single-copy sequences. Nucleotide replacements that occurred in human and chimpanzee palindrome arms over the past 7 million years are one-and-a-half times as GC-rich as the ancestral bases they replaced. Using simulations, we show that our observed pattern of nucleotide replacements is consistent with GC-biased gene conversion with a magnitude of 70%, similar to previously reported values based on analyses of human meioses. However, GC-biased gene conversion since the divergence of human and rhesus macaque explains only a fraction of the observed difference in GC content between palindrome arms and flanking sequence, suggesting that palindromes are older than 29 million years and/or had elevated GC content at the time of their formation. This work supports a greater than 2:1 preference for GC bases over AT bases during gene conversion and demonstrates that the evolution and composition of mammalian sex chromosome palindromes is strongly influenced by GC-biased gene conversion.
基因转换在广泛的分类群中存在 GC 偏向性。哺乳动物性染色体上的大片段回文结构经历了频繁的基因转换，保持着臂对臂的序列同一性大于 99%，这可能增加了它们对 GC 偏向性基因转换影响的敏感性。在这里，我们证明了在人类、黑猩猩和恒河猴的 X 染色体上保守的 12 个回文结构中存在惊人的 GC 偏向性基因转换历史。灵长类动物 X 染色体回文臂的 GC 含量明显高于侧翼单拷贝序列。在过去的 700 万年中，在人类和黑猩猩回文臂中发生的核苷酸替换比它们所取代的祖先碱基 GC 含量高 1.5 倍。通过模拟，我们表明我们观察到的核苷酸替换模式与 GC 偏向性基因转换一致，其程度为 70%，与以前基于人类减数分裂分析的报告值相似。然而，自人类和恒河猴分化以来的 GC 偏向性基因转换仅解释了回文臂和侧翼序列之间 GC 含量差异的一部分，这表明回文结构比 2900 万年还要古老，或者在形成时具有更高的 GC 含量。这项工作支持在基因转换过程中 GC 碱基对 AT 碱基的偏好大于 2:1，并表明哺乳动物性染色体回文结构的进化和组成受到 GC 偏向性基因转换的强烈影响。
