Center for the Advanced Study of Human Paleobiology, Department of Anthropology, The George Washington University, Washington, District of Columbia.
Behavioural Ecology & Ecophysiology Group, Department of Biology, University of Antwerp, Antwerp, Belgium.
Genes Brain Behav. 2019 Sep;18(7):e12582. doi: 10.1111/gbb.12582. Epub 2019 Jun 11.
Studying genetic mechanisms underlying primate brain morphology can provide insight into the evolution of human brain structure and cognition. In humans, loss-of-function mutations in the gene coding for ASPM (Abnormal Spindle Microtubule Assembly) have been associated with primary microcephaly, which is defined by a significantly reduced brain volume, intellectual disability and delayed development. However, less is known about the effects of common ASPM variation in humans and other primates. In this study, we characterized the degree of coding variation at ASPM in a large sample of chimpanzees (N = 241), and examined potential associations between genotype and various measures of brain morphology. We identified and genotyped five non-synonymous polymorphisms in exons 3 (V588G), 18 (Q2772K, K2796E, C2811Y) and 27 (I3427V). Using T1-weighted magnetic resonance imaging of brains, we measured total brain volume, cerebral gray and white matter volume, cerebral ventricular volume, and cortical surface area in the same chimpanzees. We found a potential association between ASPM V588G genotype and cerebral ventricular volume but not with the other measures. Additionally, we found that chimpanzee, bonobo, and human lineages each independently show a signature of accelerated ASPM protein evolution. Overall, our results suggest the potential effects of ASPM variation on cerebral cortical development, and emphasize the need for further functional studies. These results are the first evidence suggesting ASPM variation might play a role in shaping natural variation in brain structure in nonhuman primates.
研究灵长类动物大脑形态的遗传机制可以深入了解人类大脑结构和认知的进化。在人类中，编码 ASPM（异常纺锤体微管组装）的基因突变与原发性小头畸形有关，其特征是大脑体积明显缩小、智力障碍和发育迟缓。然而，人们对人类和其他灵长类动物中常见的 ASMP 变异的影响知之甚少。在这项研究中，我们在大量的黑猩猩样本（N=241）中描述了 ASPM 编码变异的程度，并研究了基因型与大脑形态的各种测量值之间的潜在关联。我们在 3 号外显子（V588G）、18 号外显子（Q2772K、K2796E、C2811Y）和 27 号外显子（I3427V）中鉴定并分型了五个非同义多态性。通过对大脑进行 T1 加权磁共振成像，我们在相同的黑猩猩中测量了总脑容量、大脑灰质和白质容量、脑室内容量和皮质表面积。我们发现 ASPM V588G 基因型与脑室内容量之间存在潜在关联，但与其他测量值没有关联。此外，我们发现黑猩猩、倭黑猩猩和人类的谱系都各自表现出 ASPM 蛋白进化加速的特征。总体而言，我们的结果表明 ASMP 变异可能对大脑皮质发育有潜在影响，并强调需要进一步进行功能研究。这些结果是首例表明 ASMP 变异可能在塑造非人类灵长类动物大脑结构的自然变异方面发挥作用的证据。
