AUTHOR=Yu Changping , Diao Runjie , Khan Ranjha , Deng Cheng , Ma Hui , Chang Zhijie , Jiang Xiaohua , Shi Qinghua 

TITLE=The Dispensable Roles of X-Linked Ubl4a and Its Autosomal Counterpart Ubl4b in Spermatogenesis Represent a New Evolutionary Type of X-Derived Retrogenes

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.689902

DOI=10.3389/fgene.2021.689902

ISSN=1664-8021

ABSTRACT=<p>X-derived retrogenes contribute to genetic diversity in evolution and are usually specifically expressed in testis and perform important functions during spermatogenesis. <italic>Ubl4b</italic> is an autosomal retrogene with testis-specific expression derived from <italic>Ubl4a</italic>, an X-linked housekeeping gene. In the current study, we performed phylogenetic analysis and revealed that <italic>Ubl4a</italic> and <italic>Ubl4b</italic> are subject to purifying selection and may have conserved functions in evolution. <italic>Ubl4b</italic> was knocked out in mice using CRISPR/Cas9 genome editing technology and interestingly, we found no alterations in reproductive parameters of <italic>Ubl4b<sup>–/–</sup></italic> male mice. To get insights into whether <italic>Ubl4a</italic> could compensate the absence of <italic>Ubl4b in vivo</italic>, we further obtained <italic>Ubl4a<sup>–/Y</sup>; Ubl4b<sup>–/–</sup></italic> mice that lack both <italic>Ubl4a</italic> and <italic>Ubl4b</italic>, and the double knockout (dKO) mice also displayed normal spermatogenesis, showing that <italic>Ubl4a</italic> and <italic>Ubl4b</italic> are both dispensable for spermatogenesis. Thus, through the <italic>in vivo</italic> study of UBL4A and UBL4B, we provided a direct evidence for the first time that some X chromosome-derived autosomal retrogenes can be unfunctional in spermatogenesis, which represents an additional evolutionary type of X-derived retrogenes.</p>