Selective Constraint on Noncoding Regions of Hominid Genomes

An important challenge for human evolutionary biology is to understand the genetic basis of human–chimpanzee differences. One influential idea holds that such differences depend, to a large extent, on adaptive changes in gene expression. An important step in assessing this hypothesis involves gaining a better understanding of selective constraint on noncoding regions of hominid genomes. In noncoding sequence, functional elements are frequently small and can be separated by large nonfunctional regions. For this reason, constraint in hominid genomes is likely to be patchy. Here we use conservation in more distantly related mammals and amniotes as a way of identifying small sequence windows that are likely to be functional. We find that putatively functional noncoding elements defined in this manner are subject to significant selective constraint in hominids.

人类进化生物学领域的一项重要挑战，在于阐明人类与黑猩猩差异的遗传基础。现有一项颇具影响力的假说提出，这类差异在很大程度上取决于基因表达的适应性改变。检验该假说的关键一步，在于深化对人科（hominid）基因组非编码区域所受选择约束（selective constraint）的认知。在非编码序列中，功能元件（functional elements）往往体量较小，且可被大片非功能区域分隔开。正因如此，人科基因组中的选择约束大概率呈现斑块状分布。本研究借助亲缘关系更远的哺乳类及羊膜动物（amniotes）的序列保守性，来识别潜在具备功能的小型序列窗口。我们发现，通过该方式定义的推定功能非编码元件，在人科物种中受到了显著的选择约束。