Cao Peng-Rong, Wang Lei, Jiang Yu-Chao, Yi Yin-Sha, Qu Fang, Liu Tao-Cheng, Lv Yuan
Department of Epidemiology, Medical College of Hunan Normal University, Changsha, China.
The State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology School of Life Sciences, Fudan University, Shanghai, China.
PLoS One. 2015 Mar 23;10(3):e0119651. doi: 10.1371/journal.pone.0119651. eCollection 2015.
The formation of new genes is a primary driving force of evolution in all organisms. The de novo evolution of new genes from non-protein-coding genomic regions is emerging as an important additional mechanism for novel gene creation. Y chromosomes underlie sex determination in mammals and contain genes that are required for male-specific functions. In this study, a search was undertaken for Y chromosome de novo genes derived from non-protein-coding sequences. The Y chromosome orphan gene variable charge, Y-linked (VCY)2, is an autosome-derived gene that has sequence similarity to large autosomal fragments but lacks an autosomal protein-coding homolog. VCY2 locates in the amplicon containing long DNA fragments that were transposed from autosomes to the Y chromosome before the ape-monkey split. We confirmed that VCY2 cannot be encoded by autosomes due to the presence of multiple disablers that disrupt the open reading frame, such as the absence of start or stop codons and the presence of premature stop codons. Similar observations have been made for homologs in the autosomes of the chimpanzee, gorilla, rhesus macaque, baboon and out-group marmoset, which suggests that there was a non-protein-coding ancestral VCY2 that was common to apes and monkeys that predated the transposition event. Furthermore, while protein-coding orthologs are absent, a putative non-protein-coding VCY2 with conserved disablers was identified in the rhesus macaque Y chromosome male-specific region. This finding implies that VCY2 might have not acquired its protein-coding ability before the ape-monkey split. VCY2 encodes a testis-specific expressed protein and is involved in the pathologic process of male infertility, and the acquisition of this gene might improve male fertility. This is the first evidence that de novo genes can be generated from transposed autosomal non-protein-coding segments, and this evidence provides novel insights into the evolutionary history of the Y chromosome.
新基因的形成是所有生物体进化的主要驱动力。从非蛋白质编码基因组区域从头进化出新基因正成为一种重要的新基因产生的额外机制。Y染色体是哺乳动物性别决定的基础，包含雄性特异性功能所需的基因。在本研究中，对源自非蛋白质编码序列的Y染色体从头基因进行了搜索。Y染色体孤儿基因可变电荷、Y连锁（VCY）2是一个源自常染色体的基因，与大的常染色体片段具有序列相似性，但缺乏常染色体蛋白质编码同源物。VCY2位于包含长DNA片段的扩增子中，这些片段在猿猴分化之前从常染色体转座到Y染色体。我们证实，由于存在多个破坏开放阅读框的失活因子，如起始或终止密码子的缺失以及过早终止密码子的存在，VCY2不能由常染色体编码。在黑猩猩、大猩猩、恒河猴、狒狒和外群狨猴的常染色体同源物中也有类似的观察结果，这表明在转座事件之前，猿猴有一个共同的非蛋白质编码祖先VCY2。此外，虽然不存在蛋白质编码直系同源物，但在恒河猴Y染色体雄性特异性区域鉴定出一个具有保守失活因子的推定非蛋白质编码VCY2。这一发现意味着VCY2可能在猿猴分化之前尚未获得其蛋白质编码能力。VCY2编码一种睾丸特异性表达蛋白，并参与男性不育的病理过程，该基因的获得可能会提高男性生育能力。这是第一个证明从头基因可以从转座的常染色体非蛋白质编码片段产生的证据，这一证据为Y染色体的进化历史提供了新的见解。
