Adaptive Evolution of Four Microcephaly Genes and the Evolution of Brain Size in Anthropoid Primates
Adaptive Evolution of Four Microcephaly Genes and the Evolution of Brain Size in Anthropoid Primates
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DOI：
10.1093/molbev/msq237
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发表时间：
2011-01-01
影响因子：
10.7
通讯作者：
Mundy, Nicholas I.
中科院分区：
文献类型：
--
作者：
Montgomery, Stephen H.;Capellini, Isabella;Mundy, Nicholas I.
灵长类动物大脑体积扩大的解剖学基础和适应功能已经研究了很久;然而，我们才刚刚开始了解这些进化变化的遗传基础。与人类原发性小头畸形相关的基因受到了广泛的关注，因为它们加速了沿着人类谱系的进化速度。然而，这些研究仅局限于猿类，小头症基因进化和大脑进化之间的联系存在争议。我们分析了与小头畸形相关的四个基因（ASPM，CDK 5 RAP 2，CENPJ，MCPH 1）在21个物种中的分子进化，这些物种代表了灵长类动物的所有主要分支。与流行的假设相反，正选择并不局限于或强化了沿着人类的谱系。事实上，我们表明，所有四个基因座都受到积极的选择，在整个灵长类动物的生殖。我们开发了明确定义的假设，以明确测试这些基因座上的选择是否与大脑大小的进化有关。我们发现CDK 5 RAP 2和ASPM与新生儿脑质量之间存在正相关关系，而这些基因与成人脑大小之间的关系较弱。相比之下，没有证据表明CENPJ和MCPH 1与大脑大小进化有关。ASPM和CDK 5 RAP 2进化与新生儿脑大小的关联性比与成人脑大小的关联性更强，这与这些基因座对产前神经元增殖具有直接影响一致。这些结果表明，灵长类动物的大脑大小可能至少有一个部分保守的遗传基础。我们的研究结果与以前的研究相矛盾，该研究将ASPM的适应性进化与相对皮层大小的变化联系起来;然而，我们的分析表明，这一结论并不可靠。我们的发现，两个广泛表达的基因座的编码区经历了普遍的积极选择，一个复杂的，定量的发育表型提供了一个显着的反例，通常断言的假设，顺式调控区发挥主导作用的表型进化。
The anatomical basis and adaptive function of the expansion in primate brain size have long been studied; however, we are only beginning to understand the genetic basis of these evolutionary changes. Genes linked to human primary microcephaly have received much attention as they have accelerated evolutionary rates along lineages leading to humans. However, these studies focus narrowly on apes, and the link between microcephaly gene evolution and brain evolution is disputed. We analyzed the molecular evolution of four genes associated with microcephaly (ASPM, CDK5RAP2, CENPJ, MCPH1) across 21 species representing all major clades of anthropoid primates. Contrary to prevailing assumptions, positive selection was not limited to or intensified along the lineage leading to humans. In fact we show that all four loci were subject to positive selection across the anthropoid primate phylogeny. We developed clearly defined hypotheses to explicitly test if selection on these loci was associated with the evolution of brain size. We found positive relationships between both CDK5RAP2 and ASPM and neonatal brain mass and somewhat weaker relationships between these genes and adult brain size. In contrast, there is no evidence linking CENPJ and MCPH1 to brain size evolution. The stronger association of ASPM and CDK5RAP2 evolution with neonatal brain size than with adult brain size is consistent with these loci having a direct effect on prenatal neuronal proliferation. These results suggest that primate brain size may have at least a partially conserved genetic basis. Our results contradict a previous study that linked adaptive evolution of ASPM to changes in relative cortex size; however, our analysis indicates that this conclusion is not robust. Our finding that the coding regions of two widely expressed loci has experienced pervasive positive selection in relation to a complex, quantitative developmental phenotype provides a notable counterexample to the commonly asserted hypothesis that cis-regulatory regions play a dominant role in phenotypic evolution.