Viscardi Lucas Henriques, Paixão-Côrtes Vanessa Rodrigues, Comas David, Salzano Francisco Mauro, Rovaris Diego, Bau Claiton Dotto, Amorim Carlos Eduardo G, Bortolini Maria Cátira
Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Departamento de Biologia, Instituto de Biologia, Universidade Federal da Bahia, Salvador, BA Brazil.
Genet Mol Biol. 2018 Jan-Mar;41(1):67-81. doi: 10.1590/1678-4685-GMB-2017-0308.
Hominin evolution is characterized by adaptive solutions often rooted in behavioral and cognitive changes. If balancing selection had an important and long-lasting impact on the evolution of these traits, it can be hypothesized that genes associated with them should carry an excess of shared polymorphisms (trans- SNPs) across recent Homo species. In this study, we investigate the role of balancing selection in human evolution using available exomes from modern (Homo sapiens) and archaic humans (H. neanderthalensis and Denisovan) for an excess of trans-SNP in two gene sets: one associated with the immune system (IMMS) and another one with behavioral system (BEHS). We identified a significant excess of trans-SNPs in IMMS (N=547), of which six of these located within genes previously associated with schizophrenia. No excess of trans-SNPs was found in BEHS, but five genes in this system harbor potential signals for balancing selection and are associated with psychiatric or neurodevelopmental disorders. Our approach evidenced recent Homo trans-SNPs that have been previously implicated in psychiatric diseases such as schizophrenia, suggesting that a genetic repertoire common to the immune and behavioral systems could have been maintained by balancing selection starting before the split between archaic and modern humans.
人类进化的特点是适应性解决方案往往源于行为和认知的变化。如果平衡选择对这些性状的进化产生了重要且持久的影响，那么可以推测，与这些性状相关的基因在近代人类物种中应该携带过量的共享多态性（跨物种单核苷酸多态性，trans - SNPs）。在本研究中，我们利用现代人类（智人）和古代人类（尼安德特人和丹尼索瓦人）的可用外显子组，针对两个基因集（一个与免疫系统相关，即IMMS；另一个与行为系统相关，即BEHS）中跨物种单核苷酸多态性的过量情况，研究平衡选择在人类进化中的作用。我们在IMMS中鉴定出显著过量的跨物种单核苷酸多态性（N = 547），其中有六个位于先前与精神分裂症相关的基因内。在BEHS中未发现跨物种单核苷酸多态性过量，但该系统中有五个基因带有平衡选择的潜在信号，并且与精神疾病或神经发育障碍相关。我们的方法证明了近代人类的跨物种单核苷酸多态性先前已涉及精神疾病如精神分裂症，这表明免疫和行为系统共有的基因库可能在古代人类和现代人类分化之前就通过平衡选择得以维持。
