Bekpen Cemalettin, Künzel Sven, Xie Chen, Eaaswarkhanth Muthukrishnan, Lin Yen-Lung, Gokcumen Omer, Akdis Cezmi A, Tautz Diethard
Max-Planck Institute for Evolutionary Biology, August-Thienemann Strasse 2, 24306, Plön, Germany.
Department of Biological Sciences, State University of New York at Buffalo, Buffalo, 14260-1300, NY, USA.
BMC Genomics. 2017 Mar 6;18(1):222. doi: 10.1186/s12864-017-3595-8.
Segmental duplications are an abundant source for novel gene functions and evolutionary adaptations. This mechanism of generating novelty was very active during the evolution of primates particularly in the human lineage. Here, we characterize the evolution and function of the SPATA31 gene family (former designation FAM75A), which was previously shown to be among the gene families with the strongest signal of positive selection in hominoids. The mouse homologue for this gene family is a single copy gene expressed during spermatogenesis.
We show that in primates, the SPATA31 gene duplicated into SPATA31A and SPATA31C types and broadened the expression into many tissues. Each type became further segmentally duplicated in the line towards humans with the largest number of full-length copies found for SPATA31A in humans. Copy number estimates of SPATA31A based on digital PCR show an average of 7.5 with a range of 5-11 copies per diploid genome among human individuals. The primate SPATA31 genes also acquired new protein domains that suggest an involvement in UV response and DNA repair. We generated antibodies and show that the protein is re-localized from the nucleolus to the whole nucleus upon UV-irradiation suggesting a UV damage response. We used CRISPR/Cas mediated mutagenesis to knockout copies of the gene in human primary fibroblast cells. We find that cell lines with reduced functional copies as well as naturally occurring low copy number HFF cells show enhanced sensitivity towards UV-irradiation.
The acquisition of new SPATA31 protein functions and its broadening of expression may be related to the evolution of the diurnal life style in primates that required a higher UV tolerance. The increased segmental duplications in hominoids as well as its fast evolution suggest the acquisition of further specific functions particularly in humans.
片段重复是新基因功能和进化适应的丰富来源。这种产生新特性的机制在灵长类动物的进化过程中非常活跃，尤其是在人类谱系中。在这里，我们描述了SPATA31基因家族（以前称为FAM75A）的进化和功能，该基因家族先前被证明是类人猿中具有最强正选择信号的基因家族之一。该基因家族的小鼠同源物是一个在精子发生过程中表达的单拷贝基因。
我们表明，在灵长类动物中，SPATA31基因复制为SPATA31A和SPATA31C类型，并将表达扩展到许多组织。在向人类进化的过程中，每种类型都进一步发生了片段重复，在人类中发现SPATA31A的全长拷贝数量最多。基于数字PCR的SPATA31A拷贝数估计显示，人类个体每个二倍体基因组的平均拷贝数为7.5，范围为5 - 11个拷贝。灵长类动物的SPATA31基因还获得了新的蛋白质结构域，这表明其参与紫外线反应和DNA修复。我们制备了抗体，并表明该蛋白在紫外线照射后从核仁重新定位到整个细胞核，表明存在紫外线损伤反应。我们使用CRISPR/Cas介导的诱变技术在人类原代成纤维细胞中敲除该基因的拷贝。我们发现，功能拷贝减少的细胞系以及天然存在的低拷贝数HFF细胞对紫外线照射表现出更高的敏感性。
新的SPATA31蛋白功能的获得及其表达的扩展可能与灵长类动物昼行性生活方式的进化有关，这种生活方式需要更高的紫外线耐受性。类人猿中片段重复的增加及其快速进化表明获得了进一步的特定功能，尤其是在人类中。
