Mekel-Bobrov Nitzan, Posthuma Danielle, Gilbert Sandra L, Lind Penelope, Gosso M Florencia, Luciano Michelle, Harris Sarah E, Bates Timothy C, Polderman Tinca J C, Whalley Lawrence J, Fox Helen, Starr John M, Evans Patrick D, Montgomery Grant W, Fernandes Croydon, Heutink Peter, Martin Nicholas G, Boomsma Dorret I, Deary Ian J, Wright Margaret J, de Geus Eco J C, Lahn Bruce T
Department of Human Genetics, Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637, USA.
Hum Mol Genet. 2007 Mar 15;16(6):600-8. doi: 10.1093/hmg/ddl487. Epub 2007 Jan 12.
Recent studies have made great strides towards identifying putative genetic events underlying the evolution of the human brain and its emergent cognitive capacities. One of the most intriguing findings is the recurrent identification of adaptive evolution in genes associated with primary microcephaly, a developmental disorder characterized by severe reduction in brain size and intelligence, reminiscent of the early hominid condition. This has led to the hypothesis that the adaptive evolution of these genes has contributed to the emergence of modern human cognition. As with other candidate loci, however, this hypothesis remains speculative due to the current lack of methodologies for characterizing the evolutionary function of these genes in humans. Two primary microcephaly genes, ASPM and Microcephalin, have been implicated not only in the adaptive evolution of the lineage leading to humans, but in ongoing selective sweeps in modern humans as well. The presence of both the putatively adaptive and neutral alleles at these loci provides a unique opportunity for using normal trait variation within humans to test the hypothesis that the recent selective sweeps are driven by an advantage in cognitive abilities. Here, we report a large-scale association study between the adaptive alleles of these genes and normal variation in several measures of IQ. Five independent samples were used, totaling 2393 subjects, including both family-based and population-based datasets. Our overall findings do not support a detectable association between the recent adaptive evolution of either ASPM or Microcephalin and changes in IQ. As we enter the post-genomic era, with the number of candidate loci underlying human evolution growing rapidly, our findings highlight the importance of direct experimental validation in elucidating their evolutionary role in shaping the human phenotype.
最近的研究在确定人类大脑进化及其新出现的认知能力背后的假定遗传事件方面取得了巨大进展。最引人入胜的发现之一是反复在与原发性小头畸形相关的基因中鉴定出适应性进化，原发性小头畸形是一种发育障碍，其特征是脑容量和智力严重降低，让人联想到早期原始人类的状况。这导致了一种假说，即这些基因的适应性进化促成了现代人类认知的出现。然而，与其他候选基因座一样，由于目前缺乏表征这些基因在人类中的进化功能所需的方法，这一假说仍然是推测性的。两个原发性小头畸形基因，即异常纺锤形小脑畸形相关蛋白（ASPM）和小头畸形蛋白（Microcephalin），不仅与导致人类的谱系的适应性进化有关，而且也与现代人类正在进行的选择性清除有关。这些基因座上假定的适应性等位基因和中性等位基因的存在，为利用人类正常性状变异来检验最近的选择性清除是由认知能力优势驱动这一假说提供了独特机会。在此，我们报告了这些基因的适应性等位基因与几种智商测量指标的正常变异之间的大规模关联研究。我们使用了五个独立样本，共计2393名受试者，包括基于家庭和基于人群的数据集。我们的总体研究结果不支持ASPM或Microcephalin最近的适应性进化与智商变化之间存在可检测到的关联。随着我们进入后基因组时代，随着人类进化潜在的候选基因座数量迅速增加，我们的研究结果凸显了直接实验验证在阐明它们在塑造人类表型中的进化作用方面的重要性。
