Limits...
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.

Show MeSH

Related in: MedlinePlus

Expression divergences between nine neo-Y and neo-X gene pairs. All expression assays were done in duplicate and double checked in both male individuals. Mean expression ratios of neo-Y to neo-X are shown. The genes are arranged following the order from the centromere to the distal region of the 1p+4 chromosome.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2481430&req=5

Figure 4: Expression divergences between nine neo-Y and neo-X gene pairs. All expression assays were done in duplicate and double checked in both male individuals. Mean expression ratios of neo-Y to neo-X are shown. The genes are arranged following the order from the centromere to the distal region of the 1p+4 chromosome.

Mentions: We semi-quantified and compared the mRNA abundance of neo-Y and neo-X alleles in 11 genes with mutations listed in Table 3. Consistent with our promoter assay, CLTC exhibits a lower expression level on neo-Y. We found significant expression difference between neo-Y and neo-X allele only in the gene SNX22 (Fisher's exact test, P < 0.01). However, this gene was further excluded from the result, together with SCN1A, because of their effects of allelic-biased amplification (see Materials and methods [below]). Eight of the remaining nine genes exhibited differential expression; interestingly, as many showed higher expression on neo-Y as on neo-X (4 versus 4; Figure 4). This finding suggests that neo-Y alleles can be distorted from normal expression level, either downregulated or upregulated, as a result of degenerating control of gene expression. Together with the mutation analysis results presented above, the expression patterns of the nine investigated genes exhibit a similar random inactivation mode of gene evolution on a degenerating Y chromosome proposed for D. miranda [12]. This model predicts that neo-Y genes are randomly inactivated, regardless of their level of adaptation. As shown in Figure 4, the regulation direction of neo-Y genes fluctuates along the neo-Y chromosome, and between some adjacent genes it is even opposite, suggesting that there is no large segment inactivation in the black muntjac's neo-Y chromosome. Two genes (CLTC and ZNF24) with only synonymous neo-Y mutations exhibited lower expression level, whereas two genes (SYNE1 and AKAP7) with nonsynonymous neo-Y mutations exhibited higher expression level. In addition, the human orthologs of all nine investigated genes are widely expressed housekeeping genes. Therefore, whether a neo-Y allele is subjected to expression alteration or the direction of alteration may be not strongly correlated with the characteristics of the gene.


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)

Expression divergences between nine neo-Y and neo-X gene pairs. All expression assays were done in duplicate and double checked in both male individuals. Mean expression ratios of neo-Y to neo-X are shown. The genes are arranged following the order from the centromere to the distal region of the 1p+4 chromosome.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Expression divergences between nine neo-Y and neo-X gene pairs. All expression assays were done in duplicate and double checked in both male individuals. Mean expression ratios of neo-Y to neo-X are shown. The genes are arranged following the order from the centromere to the distal region of the 1p+4 chromosome.
Mentions: We semi-quantified and compared the mRNA abundance of neo-Y and neo-X alleles in 11 genes with mutations listed in Table 3. Consistent with our promoter assay, CLTC exhibits a lower expression level on neo-Y. We found significant expression difference between neo-Y and neo-X allele only in the gene SNX22 (Fisher's exact test, P < 0.01). However, this gene was further excluded from the result, together with SCN1A, because of their effects of allelic-biased amplification (see Materials and methods [below]). Eight of the remaining nine genes exhibited differential expression; interestingly, as many showed higher expression on neo-Y as on neo-X (4 versus 4; Figure 4). This finding suggests that neo-Y alleles can be distorted from normal expression level, either downregulated or upregulated, as a result of degenerating control of gene expression. Together with the mutation analysis results presented above, the expression patterns of the nine investigated genes exhibit a similar random inactivation mode of gene evolution on a degenerating Y chromosome proposed for D. miranda [12]. This model predicts that neo-Y genes are randomly inactivated, regardless of their level of adaptation. As shown in Figure 4, the regulation direction of neo-Y genes fluctuates along the neo-Y chromosome, and between some adjacent genes it is even opposite, suggesting that there is no large segment inactivation in the black muntjac's neo-Y chromosome. Two genes (CLTC and ZNF24) with only synonymous neo-Y mutations exhibited lower expression level, whereas two genes (SYNE1 and AKAP7) with nonsynonymous neo-Y mutations exhibited higher expression level. In addition, the human orthologs of all nine investigated genes are widely expressed housekeeping genes. Therefore, whether a neo-Y allele is subjected to expression alteration or the direction of alteration may be not strongly correlated with the characteristics of the gene.

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