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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

Heterochromatin evolution on the D. busckii neo-Y.Shown is the normalized log2 enrichment level of H3K9me2 (A-C) or H3K9me3 (D-F) over genes on different chromosomes. A. Enrichment level of H3K9me2 at silent neo-Y linked genes (in blue) is significantly higher than that of the neo-X (in orange, Wilcoxon test significance level, P<0.001:***), chrX (red) and autosomes (green). B-C. ‘Metagene’ profiles for H3K9me2 enrichment. Metagene profiles scale all genes of the same chromosome into the same number of bins for calculating average enrichment frequency along the gene body (Methods and Materials). We divide genes into actively transcribed (B.) and silent (C.) genes based on the gene expression levels of neo-Y alleles. We also include the up- and down- stream 1.5kb flanking regions. D. Enrichment level of H3K9me3. E-F. Metagene profiles for H3K9me3 enrichment at active (E.) and silent (F.) genes.
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pgen.1005331.g004: Heterochromatin evolution on the D. busckii neo-Y.Shown is the normalized log2 enrichment level of H3K9me2 (A-C) or H3K9me3 (D-F) over genes on different chromosomes. A. Enrichment level of H3K9me2 at silent neo-Y linked genes (in blue) is significantly higher than that of the neo-X (in orange, Wilcoxon test significance level, P<0.001:***), chrX (red) and autosomes (green). B-C. ‘Metagene’ profiles for H3K9me2 enrichment. Metagene profiles scale all genes of the same chromosome into the same number of bins for calculating average enrichment frequency along the gene body (Methods and Materials). We divide genes into actively transcribed (B.) and silent (C.) genes based on the gene expression levels of neo-Y alleles. We also include the up- and down- stream 1.5kb flanking regions. D. Enrichment level of H3K9me3. E-F. Metagene profiles for H3K9me3 enrichment at active (E.) and silent (F.) genes.

Mentions: We analyzed the distribution of H3K9me2 and H3K9me3 at active and silent genes (expression status defined from S1 Fig), and find that both marks are significantly enriched on the dot chromosomes of D. busckii relative to autosomes (Wilcoxon test, P<0.05; see Methods, Fig 4A and 4D). H3K9me3 shows a similar level of enrichment between the neo-Y and the neo-X (Wilcoxon test, P>0.05, Fig 4D), and enrichment tends to be higher at active relative to silent genes on both the neo-X and neo-Y (Wilcoxon test P>0.05; Fig 4D–4F). In contrast, H3K9me2 levels are significantly increased at neo-Y genes relative to their neo-X homologs (Wilcoxon test, P = 0.000637, Fig 4A), particularly on those that are transcriptionally silenced (Wilcoxon test, P = 0.000381, Fig 4A–4C), and non-functional neo-Y genes show a significant increase in H3K9me2 binding relative to their neo-X homologs (Wilcoxon test, P = 0.0001494; S6 Fig). The H3K9me2 enrichment level of silent neo-Y genes is higher than that of active neo-Y genes (median value: 0.79 vs. 0.47, Wilcoxon test P = 0.089, Fig 4A), and the enrichment level of H3K9me2, but not H3K9me3, is negatively correlated with the gene expression level of neo-Y but not neo-X alleles (S7 Fig, Spearman’s rank correlation coefficient -0.23, P = 0.04). We further analyzed metagene enrichment profiles, and find both H3K9me2 and H3K9me3 to be enriched at gene bodies relative to their flanking regions. The increase of H3K9me2 enrichment on silent neo-Y genes is not restricted to gene bodies but extends into flanking regions as well (Fig 4C). These results suggest that down-regulation of neo-Y gene expression may be caused by H3K9me2 modification, but it is also possible that some genes are first silenced through mutations in their regulatory region, and then preferentially become targeted by H3K9me2. Overall, our results provide robust evidence that the neo-Y chromosome of D. busckii is becoming more heterochromatic, mediated by H3K9me2 enrichment, which further contributes to the degeneration of neo-Y genes.


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

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

Heterochromatin evolution on the D. busckii neo-Y.Shown is the normalized log2 enrichment level of H3K9me2 (A-C) or H3K9me3 (D-F) over genes on different chromosomes. A. Enrichment level of H3K9me2 at silent neo-Y linked genes (in blue) is significantly higher than that of the neo-X (in orange, Wilcoxon test significance level, P<0.001:***), chrX (red) and autosomes (green). B-C. ‘Metagene’ profiles for H3K9me2 enrichment. Metagene profiles scale all genes of the same chromosome into the same number of bins for calculating average enrichment frequency along the gene body (Methods and Materials). We divide genes into actively transcribed (B.) and silent (C.) genes based on the gene expression levels of neo-Y alleles. We also include the up- and down- stream 1.5kb flanking regions. D. Enrichment level of H3K9me3. E-F. Metagene profiles for H3K9me3 enrichment at active (E.) and silent (F.) genes.
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pgen.1005331.g004: Heterochromatin evolution on the D. busckii neo-Y.Shown is the normalized log2 enrichment level of H3K9me2 (A-C) or H3K9me3 (D-F) over genes on different chromosomes. A. Enrichment level of H3K9me2 at silent neo-Y linked genes (in blue) is significantly higher than that of the neo-X (in orange, Wilcoxon test significance level, P<0.001:***), chrX (red) and autosomes (green). B-C. ‘Metagene’ profiles for H3K9me2 enrichment. Metagene profiles scale all genes of the same chromosome into the same number of bins for calculating average enrichment frequency along the gene body (Methods and Materials). We divide genes into actively transcribed (B.) and silent (C.) genes based on the gene expression levels of neo-Y alleles. We also include the up- and down- stream 1.5kb flanking regions. D. Enrichment level of H3K9me3. E-F. Metagene profiles for H3K9me3 enrichment at active (E.) and silent (F.) genes.
Mentions: We analyzed the distribution of H3K9me2 and H3K9me3 at active and silent genes (expression status defined from S1 Fig), and find that both marks are significantly enriched on the dot chromosomes of D. busckii relative to autosomes (Wilcoxon test, P<0.05; see Methods, Fig 4A and 4D). H3K9me3 shows a similar level of enrichment between the neo-Y and the neo-X (Wilcoxon test, P>0.05, Fig 4D), and enrichment tends to be higher at active relative to silent genes on both the neo-X and neo-Y (Wilcoxon test P>0.05; Fig 4D–4F). In contrast, H3K9me2 levels are significantly increased at neo-Y genes relative to their neo-X homologs (Wilcoxon test, P = 0.000637, Fig 4A), particularly on those that are transcriptionally silenced (Wilcoxon test, P = 0.000381, Fig 4A–4C), and non-functional neo-Y genes show a significant increase in H3K9me2 binding relative to their neo-X homologs (Wilcoxon test, P = 0.0001494; S6 Fig). The H3K9me2 enrichment level of silent neo-Y genes is higher than that of active neo-Y genes (median value: 0.79 vs. 0.47, Wilcoxon test P = 0.089, Fig 4A), and the enrichment level of H3K9me2, but not H3K9me3, is negatively correlated with the gene expression level of neo-Y but not neo-X alleles (S7 Fig, Spearman’s rank correlation coefficient -0.23, P = 0.04). We further analyzed metagene enrichment profiles, and find both H3K9me2 and H3K9me3 to be enriched at gene bodies relative to their flanking regions. The increase of H3K9me2 enrichment on silent neo-Y genes is not restricted to gene bodies but extends into flanking regions as well (Fig 4C). These results suggest that down-regulation of neo-Y gene expression may be caused by H3K9me2 modification, but it is also possible that some genes are first silenced through mutations in their regulatory region, and then preferentially become targeted by H3K9me2. Overall, our results provide robust evidence that the neo-Y chromosome of D. busckii is becoming more heterochromatic, mediated by H3K9me2 enrichment, which further contributes to the degeneration of neo-Y 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