Bioinformatics, Scientific Institute IRCCS E. MEDEA, 23842, Bosisio Parini, Italy.
Department of Physiopathology and Transplantation, University of Milan, 20090, Milan, Italy.
Sci Rep. 2017 Jul 21;7(1):6116. doi: 10.1038/s41598-017-06440-4.
In addition to high intelligence, humans evolved specialized social-cognitive skills, which are specifically affected in children with autism spectrum disorder (ASD). Genes affected in ASD represent suitable candidates to study the evolution of human social cognition. We performed an evolutionary analysis on 68 genes associated to neurodevelopmental disorders; our data indicate that genetic diversity was shaped by distinct selective forces, including natural selection and introgression from archaic hominins. We discuss the possibility that segregation distortion during spermatogenesis accounts for a subset of ASD mutations. Finally, we detected modern-human-specific alleles in DYRK1A and TCF4. These variants are located within regions that display chromatin features typical of transcriptional enhancers in several brain areas, strongly suggesting a regulatory role. These SNPs thus represent candidates for association with neurodevelopmental disorders, and await experimental validation in future studies.
除了高智商外，人类还进化出了专门的社会认知技能，而患有自闭症谱系障碍（ASD）的儿童的这些技能会受到特别影响。ASD 相关基因是研究人类社会认知进化的合适候选者。我们对 68 个与神经发育障碍相关的基因进行了进化分析；我们的数据表明，遗传多样性是由不同的选择压力塑造的，包括自然选择和来自古人类的基因渗入。我们讨论了在精子发生过程中遗传分离失真是否导致了 ASD 突变的一个亚组。最后，我们在 DYRK1A 和 TCF4 中检测到了现代人特异性等位基因。这些变体位于显示出几种大脑区域转录增强子典型染色质特征的区域内，强烈暗示了其具有调节作用。因此，这些 SNP 代表了与神经发育障碍相关的候选者，有待在未来的研究中进行实验验证。
