Department of Bioscience, School of Science, Kitasato University, 1-15-1 Kitasato, Minamiku Sagamihara, Kanagawa 252-0373, Japan.
Department of Biology, McMaster University, Life Sciences Room 328, 1280 Main Street West, Hamilton, ON, Canada L8S 4K1.
Mol Biol Evol. 2022 Jul 2;39(7). doi: 10.1093/molbev/msac138.
Most vertebrate sex-determining genes (SDGs) emerge as neofunctionalized genes through duplication and/or mutation of ancestral genes that are involved with sexual differentiation. We previously demonstrated dm-W to be the SDG in the African clawed frog Xenopus laevis and found that a portion of this gene emerged from the masculinization gene dmrt1 after allotetraploidization by interspecific hybridization between two ancestral species around 17-18 Ma. dm-W has four exons consisting of a noncoding exon 1, dmrt1-derived exons 2 and 3, and an orphan exon 4 (Ex4) of unknown origin that includes coding sequence (CDS). In this study, we searched for the origin of Ex4 and investigated the function of the CDS of this exon. We found that the Ex4-CDS is derived from a noncoding portion of the hAT-10 family of DNA transposon. Evolutionary analysis of transposons and determination of the Ex4 sequences from three other species indicated that Ex4 was generated before the diversification of most or all extant allotetraploid species in subgenus Xenopus, during which time we hypothesize that transposase activity of this hAT superfamily was active. Using DNA-protein binding and transfection assays, we further demonstrate that the Ex4-encoded amino acid sequence increases the DNA-binding ability and transrepression activity of DM-W. These findings suggest that the conversion of the noncoding transposon sequence to the CDS of dm-W contributed to neofunctionalization of a new chimeric SDG in the ancestor of the allotetraploid Xenopus species, offering new insights into de novo origin and functional evolution of chimerical genes.
大多数脊椎动物性别决定基因(SDG)是通过参与性分化的祖先基因的复制和/或突变而成为新功能化基因的。我们之前证明 dm-W 是非洲爪蟾 Xenopus laevis 的 SDG,并发现该基因的一部分是在大约 17-18 Ma 由两个祖先物种之间的种间杂交引起的异源四倍化后从雄性化基因 dmrt1 中产生的。dm-W 有四个外显子,包括一个非编码外显子 1、dmrt1 衍生的外显子 2 和 3,以及一个未知起源的孤儿外显子 4(Ex4),其中包含编码序列(CDS)。在这项研究中,我们搜索了 Ex4 的起源,并研究了这个外显子的 CDS 的功能。我们发现 Ex4-CDS 源自 DNA 转座子 hAT-10 家族的非编码部分。转座子的进化分析和来自其他三个物种的 Ex4 序列的确定表明,Ex4 是在亚属 Xenopus 的大多数或所有现存异源四倍体物种多样化之前产生的,在此期间,我们假设这个 hAT 超家族的转座酶活性是活跃的。通过 DNA-蛋白结合和转染实验,我们进一步证明 Ex4 编码的氨基酸序列增加了 DM-W 的 DNA 结合能力和反式抑制活性。这些发现表明,将非编码转座子序列转换为 dm-W 的 CDS 有助于新的嵌合 SDG 在异源四倍体 Xenopus 物种的祖先中发生新功能化,为嵌合基因的从头起源和功能进化提供了新的见解。