Accelerated evolution of conserved noncoding sequences in humans
Accelerated evolution of conserved noncoding sequences in humans
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DOI：
10.1126/science.1130738
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发表时间：
2006-11-03
期刊：
影响因子：
56.9
通讯作者：
Rubin, Edward M.
中科院分区：
文献类型：
--
作者：
Prabhakar, Shyam;Noonan, James P.;Rubin, Edward M.
基因调控的变化可能影响了人类与其他哺乳动物的表型差异，但人类调控序列中适应性取代的程度仍然未知。我们确定了992个保守的非编码序列（CNSs）与人类特异性取代显着过量。这些加速元件不成比例地发现附近的基因参与神经元细胞粘附。为了评估人类非编码进化的独特性，我们研究了黑猩猩和小鼠的CNSs加速。虽然我们在黑猩猩的神经元粘附基因附近观察到了类似的富集，但加速的CNSs本身几乎没有与人类的CNSs重叠，这表明每个物种都朝着不同的神经元表型独立进化。在小鼠中加速的CNSs没有显示出对神经元细胞粘附的偏倚。我们的研究结果表明，人类进化过程中广泛的顺式调节变化可能有助于大脑发育和功能的独特人类特征。
Changes in gene regulation likely influenced the profound phenotypic divergence of humans from other mammals, but the extent of adaptive substitution in human regulatory sequences remains unknown. We identified 992 conserved noncoding sequences (CNSs) with a significant excess of human-specific substitutions. These accelerated elements were disproportionately found near genes involved in neuronal cell adhesion. To assess the uniqueness of human noncoding evolution, we examined CNSs accelerated in chimpanzee and mouse. Although we observed a similar enrichment near neuronal adhesion genes in chimpanzee, the accelerated CNSs themselves exhibited almost no overlap with those in human, suggesting independent evolution toward different neuronal phenotypes in each species. CNSs accelerated in mouse showed no bias toward neuronal cell adhesion. Our results indicate that widespread cis-regulatory changes in human evolution may have contributed to uniquely human features of brain development and function.