Ancestral Y-linked genes were maintained by translocation to the X and Y chromosomes fused to an autosomal pair in the Okinawa spiny rat Tokudaia muenninki

Two species of the genus Tokudaia lack the Y chromosome and SRY, but several Y-linked genes have been rescued by translocation or transposition to other chromosomes. Tokudaia muenninki is the only species in the genus that maintains the Y owing to sex chromosome-autosome fusions. According to previous studies, many SRY pseudocopies and other Y-linked genes have evolved by excess duplication in this species. Using RNA-seq and RT-PCR, we found that ZFY, EIF2S3Y, TSPY, UTY, DDX3Y, USP9Y, and RBMY, but not UBA1Y, had high deduced amino acid sequence similarity and similar expression patterns with other rodents, suggesting that these genes were functional. Based on FISH and quantitative real-time PCR, all of the genes except for UTY and DDX3Y were amplified on the X and Y chromosomes with approximately 10-66 copies in the male genome. In a comparative analysis of the 372.4-kb BAC sequence and Y-linked gene transcripts from T. muenninki with the mouse Y genomic sequence, we observed that multiple-copy genes in the ancestral Y genome were nonfunctional, indicating that the gene functions were assumed by amplified copies. We also found a LTR sequence at the distal end of a SRY duplication unit, suggesting that unequal sister chromatid exchange mediated by retrotransposable elements could have been involved in SRY amplification. Our results revealed that the Y-linked genes were rescued from degeneration via translocations to other sex chromosomal regions and amplification events in T. muenninki

Initiation of recombination suppression and PAR formation during the early stages of neo-sex chromosome differentiation in the Okinawa spiny rat, Tokudaia muenninki

Background: Sex chromosomes of extant eutherian species are too ancient to reveal the process that initiated sex-chromosome differentiation. By contrast, the neo-sex chromosomes generated by sex-autosome fusions of recent origin in Tokudaia muenninki are expected to be evolutionarily ‘young’, and therefore provide a good model in which to elucidate the early phases of eutherian sex chromosome evolution. Here we describe the genomic evolution of T. muenninki in neo-sex chromosome differentiation. Results: FISH mapping of a T. muenninki male, using 50 BAC clones as probes, revealed no chromosomal rearrangements between the neo-sex chromosomes. Substitution-direction analysis disclosed that sequence evolution toward GC-richness, which positively correlates with recombination activity, occurred in the peritelomeric regions, but not middle regions of the neo-sex chromosomes. In contrast, the sequence evolution toward AT-richness was observed in those pericentromeric regions. Furthermore, we showed genetic differentiation between the pericentromeric regions as well as an accelerated rate of evolution in the neo-Y region through the detection of male-specific substitutions by gene sequencing in multiple males and females, and each neo-sex–derived BAC sequencing. Conclusions: Our results suggest that recombination has been suppressed in the pericentromeric region of neo-sex chromosomes without chromosome rearrangement, whereas high levels of recombination activity is limited in the peritelomeric region of almost undifferentiated neo-sex chromosomes. We conclude that PAR might have been formed on the peritelomeric region of sex chromosomes as an independent event from spread of recombination suppression during the early stages of sex chromosome differentiation

Intramedullary injury combined with osteoporosis therapeutics regulates targeted local osteogenesis.

福岡歯科大学2022年

Mutations in the Testis-Specific Enhancer of SOX9 in the SRY Independent Sex-Determining Mechanism in the Genus Tokudaia

SRY (sex-determining region Y) is widely conserved in eutherian mammals as a sex-determining gene located on the Y chromosome. SRY proteins bind to the testis-specific enhancer of SOX9 (TES) with SF1 to upregulate SOX9 expression in undifferentiated gonads of XY embryos of humans and mice. The core region within TES, named TESCO, is an important enhancer for mammalian sex determination. We show that TESCO of the genus Tokudaia lost enhancer activity caused by mutations in its SRY and SF1 binding sites. Two species of Tokudaia do not have the Y chromosome or SRY, and one species has multiple SRYs located on the neo-Y chromosome consisting of the Y fused with an autosome. The sequence of Tokudaia TESCO exhibited more than 83% identity with mouse TESCO, however, nucleotide substitution(s) were found in two out of three SRY binding sites and in five out of six SF1 binding sites. TESCO of all species showed low enhancer activity in cells co-transfected with SRY and SF1, and SOX9 and SF1 in reporter gene assays. Mutated TESCO, in which nucleotide substitutions found in SRY and SF1 binding sites were replaced with mouse sequence, recovered the activity. Furthermore, SRYs of the SRY-positive species could not activate the mutated TESCO or mouse TESCO, suggesting that SRYs lost function as a sex-determining gene any more. Our results indicate that the SRY dependent sex-determining mechanism was lost in a common ancestor of the genus Tokudaia caused by nucleotide substitutions in SRY and SF1 binding sites after emergence of a new sex-determining gene. We present the first evidence for an intermediate stage of the switchover from SRY to a new sex-determining gene in the evolution of mammalian sex-determining mechanism

Initiation of recombination suppression and PAR formation during the early stages of neo-sex chromosome differentiation in the Okinawa spiny rat, Tokudaia muenninki

Background: Sex chromosomes of extant eutherian species are too ancient to reveal the process that initiated sex-chromosome differentiation. By contrast, the neo-sex chromosomes generated by sex-autosome fusions of recent origin in Tokudaia muenninki are expected to be evolutionarily 'young', and therefore provide a good model in which to elucidate the early phases of eutherian sex chromosome evolution. Here we describe the genomic evolution of T. muenninki in neo-sex chromosome differentiation. Results: FISH mapping of a T. muenninki male, using 50 BAC clones as probes, revealed no chromosomal rearrangements between the neo-sex chromosomes. Substitution-direction analysis disclosed that sequence evolution toward GC-richness, which positively correlates with recombination activity, occurred in the peritelomeric regions, but not middle regions of the neo-sex chromosomes. In contrast, the sequence evolution toward AT-richness was observed in those pericentromeric regions. Furthermore, we showed genetic differentiation between the pericentromeric regions as well as an accelerated rate of evolution in the neo-Y region through the detection of male-specific substitutions by gene sequencing in multiple males and females, and each neo-sex-derived BAC sequencing. Conclusions: Our results suggest that recombination has been suppressed in the pericentromeric region of neo-sex chromosomes without chromosome rearrangement, whereas high levels of recombination activity is limited in the peritelomeric region of almost undifferentiated neo-sex chromosomes. We conclude that PAR might have been formed on the peritelomeric region of sex chromosomes as an independent event from spread of recombination suppression during the early stages of sex chromosome differentiation

パイン ブーム カラ トラエナオス キョウカイ ベイグン センリョウキ ノ オキナワ イシガキジマ カラ カク オキナワ センゴシ

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