Bush Eliot C, Lahn Bruce T
Howard Hughes Medical Institute, Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.
PLoS Comput Biol. 2005 Dec;1(7):e73. doi: 10.1371/journal.pcbi.0010073. Epub 2005 Dec 16.
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.
人类进化生物学面临的一项重要挑战是理解人类与黑猩猩差异的遗传基础。一种有影响力的观点认为,此类差异在很大程度上取决于基因表达的适应性变化。评估这一假设的重要一步是更好地了解对灵长类基因组非编码区域的选择限制。在非编码序列中,功能元件通常很小,并且可能被大片非功能区域隔开。因此,灵长类基因组中的限制可能是不连续的。在这里,我们利用与人类亲缘关系更远的哺乳动物和羊膜动物中的保守性,作为识别可能具有功能的小序列窗口的一种方法。我们发现,以这种方式定义的推定功能性非编码元件在灵长类动物中受到显著的选择限制。