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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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Dendrogram constructed using noncoding sequences of neo-Y and neo-X fragments. A total of 35.1-kilobase noncoding sequences of neo-Y and neo-X alleles in the black muntjac and the orthologous sequences in the Indian muntjac as the outgroup were used to construct the dentrogram. 'BM' stands for 'male black muntjac'; 'IM' stands for 'Indian muntjac'; '1'and '2' represent the two male black muntjac individuals separately. (a) Tree constructed by neighbor-joining method. Branch lengths calculated using Kimura's two-parameter method are shown above the corresponding branches. (b) Tree constructed by maximum likelihood method. Branch lengths calculated by baseml in PAML package using 'HKY85' method were shown above the corresponding branches.
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Figure 2: Dendrogram constructed using noncoding sequences of neo-Y and neo-X fragments. A total of 35.1-kilobase noncoding sequences of neo-Y and neo-X alleles in the black muntjac and the orthologous sequences in the Indian muntjac as the outgroup were used to construct the dentrogram. 'BM' stands for 'male black muntjac'; 'IM' stands for 'Indian muntjac'; '1'and '2' represent the two male black muntjac individuals separately. (a) Tree constructed by neighbor-joining method. Branch lengths calculated using Kimura's two-parameter method are shown above the corresponding branches. (b) Tree constructed by maximum likelihood method. Branch lengths calculated by baseml in PAML package using 'HKY85' method were shown above the corresponding branches.

Mentions: Under neutrality, intraspecific genetic diversity (θ) is expected to be proportional to the effective population size (Ne) times the mutation rate (μ; specifically, θ = 4Neμ) [26]. Therefore, if recombination has authentically ceased between neo-Y and neo-X, then we would expect a reduced DNA polymorphism caused by reduced Ne for the neo-Y regions [6,27]. Otherwise, the polymorphism level of neo-Y should be similar to that of 'PAR' regions or autosomes. Consistent with the former expectation, we found a significantly lower number of segregating sites (χ2 test, P < 0.01; see Materials and methods [below]) and a lower polymorphism level of neo-Y regions (0.00168 ± 0.00120 versus 0.00190 ± 0.00029) compared with regions that undergo homologous meiotic pairing (Table 1), indicating suppression of recombination between neo-Y and neo-X. Of course, other factors including the Hill-Robertson effect, background selection, hitchhiking effect, or Muller's ratchet could have all reduced the polymorphism level within the investigated noncoding regions [6]. In contrast, the 'male-driven evolution' effect, which proposes that the neo-Y would undergo more rounds of cell division per generation in male than in female germlines, would increase the mutation rate and polymorphism level of neo-Y alleles compared with those of neo-X and autosomes [28]. Our phylogenetic analysis of neo-X and neo-Y sequences in the male black muntjac confirms that the neo-Y alleles have accumulated far more mutations than neo-X (Figure 2; statistically significant, by Tajima's relative rate tests, P < 0.001).


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)

Dendrogram constructed using noncoding sequences of neo-Y and neo-X fragments. A total of 35.1-kilobase noncoding sequences of neo-Y and neo-X alleles in the black muntjac and the orthologous sequences in the Indian muntjac as the outgroup were used to construct the dentrogram. 'BM' stands for 'male black muntjac'; 'IM' stands for 'Indian muntjac'; '1'and '2' represent the two male black muntjac individuals separately. (a) Tree constructed by neighbor-joining method. Branch lengths calculated using Kimura's two-parameter method are shown above the corresponding branches. (b) Tree constructed by maximum likelihood method. Branch lengths calculated by baseml in PAML package using 'HKY85' method were shown above the corresponding branches.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Dendrogram constructed using noncoding sequences of neo-Y and neo-X fragments. A total of 35.1-kilobase noncoding sequences of neo-Y and neo-X alleles in the black muntjac and the orthologous sequences in the Indian muntjac as the outgroup were used to construct the dentrogram. 'BM' stands for 'male black muntjac'; 'IM' stands for 'Indian muntjac'; '1'and '2' represent the two male black muntjac individuals separately. (a) Tree constructed by neighbor-joining method. Branch lengths calculated using Kimura's two-parameter method are shown above the corresponding branches. (b) Tree constructed by maximum likelihood method. Branch lengths calculated by baseml in PAML package using 'HKY85' method were shown above the corresponding branches.
Mentions: Under neutrality, intraspecific genetic diversity (θ) is expected to be proportional to the effective population size (Ne) times the mutation rate (μ; specifically, θ = 4Neμ) [26]. Therefore, if recombination has authentically ceased between neo-Y and neo-X, then we would expect a reduced DNA polymorphism caused by reduced Ne for the neo-Y regions [6,27]. Otherwise, the polymorphism level of neo-Y should be similar to that of 'PAR' regions or autosomes. Consistent with the former expectation, we found a significantly lower number of segregating sites (χ2 test, P < 0.01; see Materials and methods [below]) and a lower polymorphism level of neo-Y regions (0.00168 ± 0.00120 versus 0.00190 ± 0.00029) compared with regions that undergo homologous meiotic pairing (Table 1), indicating suppression of recombination between neo-Y and neo-X. Of course, other factors including the Hill-Robertson effect, background selection, hitchhiking effect, or Muller's ratchet could have all reduced the polymorphism level within the investigated noncoding regions [6]. In contrast, the 'male-driven evolution' effect, which proposes that the neo-Y would undergo more rounds of cell division per generation in male than in female germlines, would increase the mutation rate and polymorphism level of neo-Y alleles compared with those of neo-X and autosomes [28]. Our phylogenetic analysis of neo-X and neo-Y sequences in the male black muntjac confirms that the neo-Y alleles have accumulated far more mutations than neo-X (Figure 2; statistically significant, by Tajima's relative rate tests, P < 0.001).

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