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Ancestral Chromatin Configuration Constrains Chromatin Evolution on Differentiating Sex Chromosomes in Drosophila.

Zhou Q, Bachtrog D - PLoS Genet. (2015)

Bottom Line: We show that the neo-sex chromosomes formed <1 million years ago, but nearly 60% of neo-Y linked genes have already become non-functional.Expression levels are generally lower for the neo-Y alleles relative to their neo-X homologs, and the silencing heterochromatin mark H3K9me2, but not H3K9me3, is significantly enriched on silenced neo-Y genes.Yet, neo-X genes are transcriptionally more active in males, relative to females, suggesting the evolution of incipient dosage compensation on the neo-X.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Biology, University of California Berkeley, Berkeley, California, United States of America.

ABSTRACT
Sex chromosomes evolve distinctive types of chromatin from a pair of ancestral autosomes that are usually euchromatic. In Drosophila, the dosage-compensated X becomes enriched for hyperactive chromatin in males (mediated by H4K16ac), while the Y chromosome acquires silencing heterochromatin (enriched for H3K9me2/3). Drosophila autosomes are typically mostly euchromatic but the small dot chromosome has evolved a heterochromatin-like milieu (enriched for H3K9me2/3) that permits the normal expression of dot-linked genes, but which is different from typical pericentric heterochromatin. In Drosophila busckii, the dot chromosomes have fused to the ancestral sex chromosomes, creating a pair of 'neo-sex' chromosomes. Here we collect genomic, transcriptomic and epigenomic data from D. busckii, to investigate the evolutionary trajectory of sex chromosomes from a largely heterochromatic ancestor. We show that the neo-sex chromosomes formed <1 million years ago, but nearly 60% of neo-Y linked genes have already become non-functional. Expression levels are generally lower for the neo-Y alleles relative to their neo-X homologs, and the silencing heterochromatin mark H3K9me2, but not H3K9me3, is significantly enriched on silenced neo-Y genes. Despite rampant neo-Y degeneration, we find that the neo-X is deficient for the canonical histone modification mark of dosage compensation (H4K16ac), relative to autosomes or the compensated ancestral X chromosome, possibly reflecting constraints imposed on evolving hyperactive chromatin in an originally heterochromatic environment. Yet, neo-X genes are transcriptionally more active in males, relative to females, suggesting the evolution of incipient dosage compensation on the neo-X. Our data show that Y degeneration proceeds quickly after sex chromosomes become established through genomic and epigenetic changes, and are consistent with the idea that the evolution of sex-linked chromatin is influenced by its ancestral configuration.

No MeSH data available.


Related in: MedlinePlus

Functional degeneration of neo-Y genes.A. Composition of neo-Y linked genes. We show numbers of putative functional genes (‘Intact’), genes with premature stop codons (‘PTC’) and/or frameshift (‘Shift’) mutations on the neo-Y. B. Boxplots of gene expression level on each chromosome. We divide neo-sex linked genes according to the functional status of the neo-Y genes: functional (func) neo-Y genes, and their diploid (dpd) neo-X homologs; non-functional (psd) neo-Y genes and their hemizygous (hmz) neo-X homologs. The former group of neo-sex linked genes shows a higher expression level than the latter. C. Allelic expression bias of neo-sex linked genes in male adults. Shown are the log ratios of neo-X expression vs. neo-Y expression along the neo-sex chromosome, with putatively functional neo-Y genes in red and pseudogenes in green. We also plot the loess smooth lines separately for the two categories of genes, in order to show the local variation of the log ratio along the chromosome position. Any genes above 0 have higher neo-X expression relative to the neo-Y. D. Sex-bias expression of neo-sex linked genes. We show the expression difference between sexes for neo-sex linked genes, with neo-X/Y gene expression level combined in male, and only neo-X gene expression in female. E. Correlation between relative neo-sex allelic expression vs. sex-biased expression and relative neo-X expression. Shown are the ratios of neo-X vs. neo-Y expression level for neo-sex linked genes, vs. their expression ratio between sexes (in blue), and the ratio of neo-X expression in male vs. that in female (in orange), as well as their linear regression lines. F. Density plot of the ratios of male neo-sex alleles (neo-X in orange, neo-Y in blue) vs. female expression levels. Assuming an equal expression level between sexes, we expect the distribution of relative neo-X alleles’ expression to be around half of the female expression level (dashed line).
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pgen.1005331.g003: Functional degeneration of neo-Y genes.A. Composition of neo-Y linked genes. We show numbers of putative functional genes (‘Intact’), genes with premature stop codons (‘PTC’) and/or frameshift (‘Shift’) mutations on the neo-Y. B. Boxplots of gene expression level on each chromosome. We divide neo-sex linked genes according to the functional status of the neo-Y genes: functional (func) neo-Y genes, and their diploid (dpd) neo-X homologs; non-functional (psd) neo-Y genes and their hemizygous (hmz) neo-X homologs. The former group of neo-sex linked genes shows a higher expression level than the latter. C. Allelic expression bias of neo-sex linked genes in male adults. Shown are the log ratios of neo-X expression vs. neo-Y expression along the neo-sex chromosome, with putatively functional neo-Y genes in red and pseudogenes in green. We also plot the loess smooth lines separately for the two categories of genes, in order to show the local variation of the log ratio along the chromosome position. Any genes above 0 have higher neo-X expression relative to the neo-Y. D. Sex-bias expression of neo-sex linked genes. We show the expression difference between sexes for neo-sex linked genes, with neo-X/Y gene expression level combined in male, and only neo-X gene expression in female. E. Correlation between relative neo-sex allelic expression vs. sex-biased expression and relative neo-X expression. Shown are the ratios of neo-X vs. neo-Y expression level for neo-sex linked genes, vs. their expression ratio between sexes (in blue), and the ratio of neo-X expression in male vs. that in female (in orange), as well as their linear regression lines. F. Density plot of the ratios of male neo-sex alleles (neo-X in orange, neo-Y in blue) vs. female expression levels. Assuming an equal expression level between sexes, we expect the distribution of relative neo-X alleles’ expression to be around half of the female expression level (dashed line).

Mentions: We annotate a total of 86 neo-sex linked genes (vs. 80 protein-coding genes on the D. melanogaster dot chromosome, see notes in Materials and Methods), all of which show the same level of read depth between sexes (S2 Fig). Thus, unlike on the older neo-Y chromosome of D. miranda [11], none of the protein-coding genes has yet been deleted from the neo-Y of D. busckii. However, we find male-specific SNPs or indels (i.e., mutations on the neo-Y) that cause premature stop codons and/or frameshift mutations in 50 neo-sex linked genes, implying that there is a large number of genes on the neo-Y that supposedly have lost their normal functions (Fig 3A). The proportion of putative non-functional genes (58.2%) is much higher on the neo-Y of D. busckii than on that of D. miranda (34.2%) [11]. This is unexpected, since there has been less time for degeneration on the younger neo-Y chromosome of D. busckii. In addition, the much smaller size of the dot chromosome predicts weaker effects of Hill-Robertson interference [10,39] and thus a lower rate of degeneration on the D. busckii neo-Y. However, simulation results have shown that the effects of interference asymptote quite fast with the number of genes [40]. Several other factors could help to explain the large fraction of non-functional genes on the recently formed neo-Y of D. busckii. First, genes located on the dot generally show lower levels of evolutionary constraint [41,42]. Consistent with reduced levels of purifying selection on dot-linked genes, we find that the neo-X alleles show a significantly lower level of codon usage bias than genes on autosomes and the X chromosome (Wilcoxon test, P<0.05; S3 Fig). Note that it is possible that selection for optimal codon usage has become more efficient for dot-linked genes on the neo-X since the dot/X fusion, which may have placed them within a more highly recombining environment, as has been observed for D. willistoni [43]. In this case, ancestral levels of codon usage bias may have been even lower for dot-linked genes.


Ancestral Chromatin Configuration Constrains Chromatin Evolution on Differentiating Sex Chromosomes in Drosophila.

Zhou Q, Bachtrog D - PLoS Genet. (2015)

Functional degeneration of neo-Y genes.A. Composition of neo-Y linked genes. We show numbers of putative functional genes (‘Intact’), genes with premature stop codons (‘PTC’) and/or frameshift (‘Shift’) mutations on the neo-Y. B. Boxplots of gene expression level on each chromosome. We divide neo-sex linked genes according to the functional status of the neo-Y genes: functional (func) neo-Y genes, and their diploid (dpd) neo-X homologs; non-functional (psd) neo-Y genes and their hemizygous (hmz) neo-X homologs. The former group of neo-sex linked genes shows a higher expression level than the latter. C. Allelic expression bias of neo-sex linked genes in male adults. Shown are the log ratios of neo-X expression vs. neo-Y expression along the neo-sex chromosome, with putatively functional neo-Y genes in red and pseudogenes in green. We also plot the loess smooth lines separately for the two categories of genes, in order to show the local variation of the log ratio along the chromosome position. Any genes above 0 have higher neo-X expression relative to the neo-Y. D. Sex-bias expression of neo-sex linked genes. We show the expression difference between sexes for neo-sex linked genes, with neo-X/Y gene expression level combined in male, and only neo-X gene expression in female. E. Correlation between relative neo-sex allelic expression vs. sex-biased expression and relative neo-X expression. Shown are the ratios of neo-X vs. neo-Y expression level for neo-sex linked genes, vs. their expression ratio between sexes (in blue), and the ratio of neo-X expression in male vs. that in female (in orange), as well as their linear regression lines. F. Density plot of the ratios of male neo-sex alleles (neo-X in orange, neo-Y in blue) vs. female expression levels. Assuming an equal expression level between sexes, we expect the distribution of relative neo-X alleles’ expression to be around half of the female expression level (dashed line).
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pgen.1005331.g003: Functional degeneration of neo-Y genes.A. Composition of neo-Y linked genes. We show numbers of putative functional genes (‘Intact’), genes with premature stop codons (‘PTC’) and/or frameshift (‘Shift’) mutations on the neo-Y. B. Boxplots of gene expression level on each chromosome. We divide neo-sex linked genes according to the functional status of the neo-Y genes: functional (func) neo-Y genes, and their diploid (dpd) neo-X homologs; non-functional (psd) neo-Y genes and their hemizygous (hmz) neo-X homologs. The former group of neo-sex linked genes shows a higher expression level than the latter. C. Allelic expression bias of neo-sex linked genes in male adults. Shown are the log ratios of neo-X expression vs. neo-Y expression along the neo-sex chromosome, with putatively functional neo-Y genes in red and pseudogenes in green. We also plot the loess smooth lines separately for the two categories of genes, in order to show the local variation of the log ratio along the chromosome position. Any genes above 0 have higher neo-X expression relative to the neo-Y. D. Sex-bias expression of neo-sex linked genes. We show the expression difference between sexes for neo-sex linked genes, with neo-X/Y gene expression level combined in male, and only neo-X gene expression in female. E. Correlation between relative neo-sex allelic expression vs. sex-biased expression and relative neo-X expression. Shown are the ratios of neo-X vs. neo-Y expression level for neo-sex linked genes, vs. their expression ratio between sexes (in blue), and the ratio of neo-X expression in male vs. that in female (in orange), as well as their linear regression lines. F. Density plot of the ratios of male neo-sex alleles (neo-X in orange, neo-Y in blue) vs. female expression levels. Assuming an equal expression level between sexes, we expect the distribution of relative neo-X alleles’ expression to be around half of the female expression level (dashed line).
Mentions: We annotate a total of 86 neo-sex linked genes (vs. 80 protein-coding genes on the D. melanogaster dot chromosome, see notes in Materials and Methods), all of which show the same level of read depth between sexes (S2 Fig). Thus, unlike on the older neo-Y chromosome of D. miranda [11], none of the protein-coding genes has yet been deleted from the neo-Y of D. busckii. However, we find male-specific SNPs or indels (i.e., mutations on the neo-Y) that cause premature stop codons and/or frameshift mutations in 50 neo-sex linked genes, implying that there is a large number of genes on the neo-Y that supposedly have lost their normal functions (Fig 3A). The proportion of putative non-functional genes (58.2%) is much higher on the neo-Y of D. busckii than on that of D. miranda (34.2%) [11]. This is unexpected, since there has been less time for degeneration on the younger neo-Y chromosome of D. busckii. In addition, the much smaller size of the dot chromosome predicts weaker effects of Hill-Robertson interference [10,39] and thus a lower rate of degeneration on the D. busckii neo-Y. However, simulation results have shown that the effects of interference asymptote quite fast with the number of genes [40]. Several other factors could help to explain the large fraction of non-functional genes on the recently formed neo-Y of D. busckii. First, genes located on the dot generally show lower levels of evolutionary constraint [41,42]. Consistent with reduced levels of purifying selection on dot-linked genes, we find that the neo-X alleles show a significantly lower level of codon usage bias than genes on autosomes and the X chromosome (Wilcoxon test, P<0.05; S3 Fig). Note that it is possible that selection for optimal codon usage has become more efficient for dot-linked genes on the neo-X since the dot/X fusion, which may have placed them within a more highly recombining environment, as has been observed for D. willistoni [43]. In this case, ancestral levels of codon usage bias may have been even lower for dot-linked genes.

Bottom Line: We show that the neo-sex chromosomes formed <1 million years ago, but nearly 60% of neo-Y linked genes have already become non-functional.Expression levels are generally lower for the neo-Y alleles relative to their neo-X homologs, and the silencing heterochromatin mark H3K9me2, but not H3K9me3, is significantly enriched on silenced neo-Y genes.Yet, neo-X genes are transcriptionally more active in males, relative to females, suggesting the evolution of incipient dosage compensation on the neo-X.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Biology, University of California Berkeley, Berkeley, California, United States of America.

ABSTRACT
Sex chromosomes evolve distinctive types of chromatin from a pair of ancestral autosomes that are usually euchromatic. In Drosophila, the dosage-compensated X becomes enriched for hyperactive chromatin in males (mediated by H4K16ac), while the Y chromosome acquires silencing heterochromatin (enriched for H3K9me2/3). Drosophila autosomes are typically mostly euchromatic but the small dot chromosome has evolved a heterochromatin-like milieu (enriched for H3K9me2/3) that permits the normal expression of dot-linked genes, but which is different from typical pericentric heterochromatin. In Drosophila busckii, the dot chromosomes have fused to the ancestral sex chromosomes, creating a pair of 'neo-sex' chromosomes. Here we collect genomic, transcriptomic and epigenomic data from D. busckii, to investigate the evolutionary trajectory of sex chromosomes from a largely heterochromatic ancestor. We show that the neo-sex chromosomes formed <1 million years ago, but nearly 60% of neo-Y linked genes have already become non-functional. Expression levels are generally lower for the neo-Y alleles relative to their neo-X homologs, and the silencing heterochromatin mark H3K9me2, but not H3K9me3, is significantly enriched on silenced neo-Y genes. Despite rampant neo-Y degeneration, we find that the neo-X is deficient for the canonical histone modification mark of dosage compensation (H4K16ac), relative to autosomes or the compensated ancestral X chromosome, possibly reflecting constraints imposed on evolving hyperactive chromatin in an originally heterochromatic environment. Yet, neo-X genes are transcriptionally more active in males, relative to females, suggesting the evolution of incipient dosage compensation on the neo-X. Our data show that Y degeneration proceeds quickly after sex chromosomes become established through genomic and epigenetic changes, and are consistent with the idea that the evolution of sex-linked chromatin is influenced by its ancestral configuration.

No MeSH data available.


Related in: MedlinePlus