title: Independent birth of a novel TRIMCyp in Tupaia belangeri with a divergent function from its paralog TRIM5.
abstract: The origin of novel genes and their evolutionary fates are long-standing questions in evolutionary biology. These questions become more complicated for genes conserved across various lineages, such as TRIM5, an antiretroviral restriction factor and a retrovirus capsid sensor in immune signaling. TRIM5 has been subjected to numerous pathogenic challenges and undergone dynamic evolution, making it an excellent example for studying gene diversification. Previous studies among several species showed that TRIM5 gained genetic and functional novelty in a lineage-specific manner, either through gene duplication or a cyclophilin A retrotransposing into the TRIM5 locus, creating the gene fusion known as TRIM5-Cyclophilin A (TRIMCyp). To date, the general pattern of TRIM5 across the mammalian lineage remains elusive. In this study, we surveyed 36 mammalian genomes to verify a potentially novel TRIM5 pattern that uniquely seems to have occurred in tree shrews (Tupaia belangeri), and found that both gene duplication and retrotransposition worked jointly to form a specific TRIM5/TRIMCyp cluster not found among other mammals. Evolutionary analyses showed that tree shrew TRIMCyp (tsTRIMCyp) originated independently in comparison with previously reported TRIMCyps and underwent strong positive selection, whereas no signal of positive selection was detected for other tree shrew TRIM5 (tsTRIM5) genes. Functional assay results suggest a functional divergence between tsTRIMCyp and its closest paralog TRIM5-4, likely reflecting different fates under diverse evolutionary forces. These findings present a rare example of novel gene origination resulting from a combination of gene duplication, retrotransposition, and exon shuffling processes, providing a new paradigm to study genetic innovations and evolutionary fates of duplicated genes.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Mu
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China.
authors.forename: Jia-Wu
authors.initials: JW
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
authors.forename: Feng-Liang
authors.initials: FL
authors.lastname: Liu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China.
authors.forename: Ren-Rong
authors.initials: RR
authors.lastname: Tian
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China University of Science and Technology of China, Hefei, China.
authors.forename: Hong-Yi
authors.initials: HY
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
authors.forename: Jian-Bao
authors.initials: JB
authors.lastname: Han
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China ship@mail.kiz.ac.cn zhengyt@mail.kiz.ac.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Shi
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China Kunming Primate Research Center, Chinese Academy of Sciences, Kunming, Yunnan, China ship@mail.kiz.ac.cn zhengyt@mail.kiz.ac.cn.
authors.forename: Yong-Tang
authors.initials: YT
authors.lastname: Zheng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D021984:Cyclophilin A / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D005091:Exons; D016368:Frameshift Mutation; D020440:Gene Duplication; D015870:Gene Expression; D007438:Introns; D008969:Molecular Sequence Data; D050506:Mutant Chimeric Proteins / Q000235:genetics* / Q000378:metabolism; D018626:Retroelements; D012641:Selection, Genetic; D016415:Sequence Alignment; D014417:Tupaia / Q000235:genetics* / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D002352:Carrier Proteins; D050506:Mutant Chimeric Proteins; D018626:Retroelements; D021984:Cyclophilin A
keywords: TRIM5α; TRIMCyp; functional divergence; gene duplication; positive selection; retrotransposition; tree shrew