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Neo-sex chromosomes in the black muntjac recapitulate incipient evolution of mammalian sex chromosomes.

Zhou Q, Wang J, Huang L, Nie W, Wang J, Liu Y, Zhao X, Yang F, Wang W - Genome Biol. (2008)

Bottom Line: We compared patterns of genome evolution in 35-kilobase noncoding regions and 23 gene pairs on the homologous neo-sex chromosomes.In vivo assays characterized a neo-Y insertion in the promoter of the CLTC gene that causes a significant reduction in allelic expression.The nascent neo-sex chromosome system of black muntjacs is a valuable model in which to study the evolution of sex chromosomes in mammals.

View Article: PubMed Central - HTML - PubMed

Affiliation: CAS-Max Planck Junior Research Group, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, People's Republic of China.

ABSTRACT

Background: The regular mammalian X and Y chromosomes diverged from each other at least 166 to 148 million years ago, leaving few traces of their early evolution, including degeneration of the Y chromosome and evolution of dosage compensation.

Results: We studied the intriguing case of black muntjac, in which a recent X-autosome fusion and a subsequent large autosomal inversion within just the past 0.5 million years have led to inheritance patterns identical to the traditional X-Y (neo-sex chromosomes). We compared patterns of genome evolution in 35-kilobase noncoding regions and 23 gene pairs on the homologous neo-sex chromosomes. We found that neo-Y alleles have accumulated more mutations, comprising a wide variety of mutation types, which indicates cessation of recombination and is consistent with an ongoing neo-Y degeneration process. Putative deleterious mutations were observed in coding regions of eight investigated genes as well as cis-regulatory regions of two housekeeping genes. In vivo assays characterized a neo-Y insertion in the promoter of the CLTC gene that causes a significant reduction in allelic expression. A neo-Y-linked deletion in the 3'-untranslated region of gene SNX22 abolished a microRNA target site. Finally, expression analyses revealed complex patterns of expression divergence between neo-Y and neo-X alleles.

Conclusion: The nascent neo-sex chromosome system of black muntjacs is a valuable model in which to study the evolution of sex chromosomes in mammals. Our results illustrate the degeneration scenarios in various genomic regions. Of particular importance, we report--for the first time--that regulatory mutations were probably able to accelerate the degeneration process of Y and contribute to further evolution of dosage compensation.

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Mutation in the promoter of CLTC gene severely causes downregulation of the neo-Y copy. Dual-reporter assay of promoter activities of CLTC. Standard error among triplicates was shown on the bar.
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Figure 3: Mutation in the promoter of CLTC gene severely causes downregulation of the neo-Y copy. Dual-reporter assay of promoter activities of CLTC. Standard error among triplicates was shown on the bar.

Mentions: We detected neo-Y specific mutations shared by both males present in the investigated regions in three out of eight genes (see Additional Data File 3). In order to assess the effect of these mutations on gene expression, allelic promoters were subsequently cloned into pGL3-Basic plasmid in front of a firefly luciferase reporter gene. Each plasmid was mixed with a plasmid (pRLs-TK) containing a constitutive promoter driving sea-pansy luciferase reporter gene and co-transfected into Hela cells and male black muntjac fibroblast cells. The ratios of firefly luciferase to sea-pansy luciferase, representing normalized promoter activity, were compared between neo-Y-linked promoters and neo-X-linked promoters. We found a significant decrease in neo-Y promoter activity in both Hela and black muntjac cell lines for the CLTC gene (Figure 3). We did not detect promoter activities for the cloned fragments of other two genes; specifically, there is no detectable expression of the reporter genes using the cloned fragments as the promoters. The only detected neo-Y specific mutation is a 1 base pair (bp) insertion 55 base pairs upstream of the putative TSS of the CLTC gene shared by both males (Additional data file 3). It is probably the mutation responsible for reducing the transcription level of neo-Y, given that this region was proposed to contribute positively to the core promoter activity by a recent comprehensive analysis of 387 promoter structures in humans [47].


Neo-sex chromosomes in the black muntjac recapitulate incipient evolution of mammalian sex chromosomes.

Zhou Q, Wang J, Huang L, Nie W, Wang J, Liu Y, Zhao X, Yang F, Wang W - Genome Biol. (2008)

Mutation in the promoter of CLTC gene severely causes downregulation of the neo-Y copy. Dual-reporter assay of promoter activities of CLTC. Standard error among triplicates was shown on the bar.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2481430&req=5

Figure 3: Mutation in the promoter of CLTC gene severely causes downregulation of the neo-Y copy. Dual-reporter assay of promoter activities of CLTC. Standard error among triplicates was shown on the bar.
Mentions: We detected neo-Y specific mutations shared by both males present in the investigated regions in three out of eight genes (see Additional Data File 3). In order to assess the effect of these mutations on gene expression, allelic promoters were subsequently cloned into pGL3-Basic plasmid in front of a firefly luciferase reporter gene. Each plasmid was mixed with a plasmid (pRLs-TK) containing a constitutive promoter driving sea-pansy luciferase reporter gene and co-transfected into Hela cells and male black muntjac fibroblast cells. The ratios of firefly luciferase to sea-pansy luciferase, representing normalized promoter activity, were compared between neo-Y-linked promoters and neo-X-linked promoters. We found a significant decrease in neo-Y promoter activity in both Hela and black muntjac cell lines for the CLTC gene (Figure 3). We did not detect promoter activities for the cloned fragments of other two genes; specifically, there is no detectable expression of the reporter genes using the cloned fragments as the promoters. The only detected neo-Y specific mutation is a 1 base pair (bp) insertion 55 base pairs upstream of the putative TSS of the CLTC gene shared by both males (Additional data file 3). It is probably the mutation responsible for reducing the transcription level of neo-Y, given that this region was proposed to contribute positively to the core promoter activity by a recent comprehensive analysis of 387 promoter structures in humans [47].

Bottom Line: We compared patterns of genome evolution in 35-kilobase noncoding regions and 23 gene pairs on the homologous neo-sex chromosomes.In vivo assays characterized a neo-Y insertion in the promoter of the CLTC gene that causes a significant reduction in allelic expression.The nascent neo-sex chromosome system of black muntjacs is a valuable model in which to study the evolution of sex chromosomes in mammals.

View Article: PubMed Central - HTML - PubMed

Affiliation: CAS-Max Planck Junior Research Group, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, People's Republic of China.

ABSTRACT

Background: The regular mammalian X and Y chromosomes diverged from each other at least 166 to 148 million years ago, leaving few traces of their early evolution, including degeneration of the Y chromosome and evolution of dosage compensation.

Results: We studied the intriguing case of black muntjac, in which a recent X-autosome fusion and a subsequent large autosomal inversion within just the past 0.5 million years have led to inheritance patterns identical to the traditional X-Y (neo-sex chromosomes). We compared patterns of genome evolution in 35-kilobase noncoding regions and 23 gene pairs on the homologous neo-sex chromosomes. We found that neo-Y alleles have accumulated more mutations, comprising a wide variety of mutation types, which indicates cessation of recombination and is consistent with an ongoing neo-Y degeneration process. Putative deleterious mutations were observed in coding regions of eight investigated genes as well as cis-regulatory regions of two housekeeping genes. In vivo assays characterized a neo-Y insertion in the promoter of the CLTC gene that causes a significant reduction in allelic expression. A neo-Y-linked deletion in the 3'-untranslated region of gene SNX22 abolished a microRNA target site. Finally, expression analyses revealed complex patterns of expression divergence between neo-Y and neo-X alleles.

Conclusion: The nascent neo-sex chromosome system of black muntjacs is a valuable model in which to study the evolution of sex chromosomes in mammals. Our results illustrate the degeneration scenarios in various genomic regions. Of particular importance, we report--for the first time--that regulatory mutations were probably able to accelerate the degeneration process of Y and contribute to further evolution of dosage compensation.

Show MeSH
Related in: MedlinePlus