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Avian W and mammalian Y chromosomes convergently retained dosage-sensitive regulators

Abstract

After birds diverged from mammals, different ancestral autosomes evolved into sex chromosomes in each lineage. In birds, females are ZW and males are ZZ, but in mammals females are XX and males are XY. We sequenced the chicken W chromosome, compared its gene content with our reconstruction of the ancestral autosomes, and followed the evolutionary trajectory of ancestral W-linked genes across birds. Avian W chromosomes evolved in parallel with mammalian Y chromosomes, preserving ancestral genes through selection to maintain the dosage of broadly expressed regulators of key cellular processes. We propose that, like the human Y chromosome, the chicken W chromosome is essential for embryonic viability of the heterogametic sex. Unlike other sequenced sex chromosomes, the chicken W chromosome did not acquire and amplify genes specifically expressed in reproductive tissues. We speculate that the pressures that drive the acquisition of reproduction-related genes on sex chromosomes may be specific to the male germ line.

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Figure 1: Structure of the chicken W chromosome.
Figure 2: Chicken W-chromosome genes are broadly expressed across adult somatic tissues.
Figure 3: Ancestral Z–W gene pairs from 14 avian species.
Figure 4: Factors in the survival of Z–W gene pairs.
Figure 5: Regulatory annotations of chicken ancestral Z–W gene pairs.

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Acknowledgements

We thank M. Delany (University of California, Davis) for UCD001 DNA, A. Vignal and M. Morrison (INRA Toulouse) for ChickRH6 radiation hybrid panel DNA, M. Lovett (Washington University, St. Louis) for chicken embryonic fibroblasts, C. Friedman and B. Trask for flow-sorted chicken W chromosomes, F. McCarthy for permission to use the Chickspress RNA–seq data set (PRJNA204941), and the “Chromas” Saint-Petersburg University Resource Center and L. Rapoport for technical assistance. This work was supported by the National Institutes of Health and the Howard Hughes Medical Institute. S.G. and E.G. were supported by the Russian Foundation of Basic Research (grant 16-04-01823a).

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Authors and Affiliations

Authors

Contributions

D.W.B., H.S., W.C.W., A.G.C., E.G., R.K.W., and D.C.P. planned the project. D.W.B., H.S., T.-J.C., D.L., and N.C. developed female-specific sequence-tagged sites. D.W.B., H.S., T.-J.C., and L.B. performed clone mapping. D.W.B., T.-J.C., N.K., T.G., and C.K. performed clone sequencing. S.G. and T.P. performed FISH analyses. D.W.B. and T.-J.C. performed RH mapping. D.W.B. and H.S. performed sequence analyses. D.W.B. and D.C.P. wrote the manuscript.

Corresponding author

Correspondence to David C Page.

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Integrated supplementary information

Supplementary Figure 1 Phase-contrast and fluorescence images of lampbrush W-chromosome spreads

(a,f,k) Images of chicken Z–W lampbrush bivalents in phase contrast, oriented with the terminal giant lumpy (TGL) loops and the W chromosome at the top and the Z chromosome at the bottom. Scale bar, 10 μm. (b,g,l) FISH localization of BAC probes (red) on the same lampbrush chromosomes counterstained with DAPI (blue). (ce,hj,mo) Magnification showing the DAPI-intense chromomeres of the W chromosome (c,h,m), the BAC hybridization signal (d,i,n), and the merged image (e,j,o). Chomomere 1 is furthest from the chiasma, and chromomere 7 is adjacent to the chiasma. CH261-75N4 localizes to chromomere 2 (b,e), CH261-107E4 localizes to chromomere 4 (g, j), and CH261-114G22 localizes to chromomere 7 (l,o).

Supplementary Figure 2 Dot plots of the pseudoautosomal region and the HINTW region.

Dot plots of nucleotide sequence identity in a window size of 50 bp and a step size of 1 bp. (a) Rectangular dot plot showing nucleotide identity between the most distal clones from the short arms of the W and Z chromosomes. The pseudoautosomal region of the Z and W chromosomes begins in telomeric repeats near the TCF4 gene. (b) Triangular dot plot showing nucleotide identity on the W chromosome in the 100 kb adjacent to the HINTW array. Two copies of HINTW are tandemly repeated outside the array.

Supplementary Figure 3 Ancestrally broad expression of Z–W pairs.

Violin plots marked with the median (black circle) and interquartile range (black bar) comparing the annotations of the human orthologs of ancestral Z–W gene pairs identified in chicken (dark pink); 4 species (chicken, collared flycatcher, crested ibis, and emu) (medium pink); and all 14 published female avian genomes (light pink) versus the human orthologs of the remainder of ancestral Z genes (light yellow). P values obtained using one-tailed Mann–Whitney U tests are reported with the associated test statistic, U. (a) The human orthologs of ancestral Z–W pairs are more broadly expressed in adult human tissues than other ancestral Z genes. Chicken Z–W pairs n = 26, other ancestral Z genes n = 516, P < 1.6 × 10–3, U = 9,012; 4 species Z–W pairs n = 70, other ancestral Z genes n = 472, P < 0.047, U = 18,563; 14 species Z–W pairs n = 133, other ancestral Z genes n = 409, P < 0.13, U = 28,960. (b) The human orthologs of ancestral Z–W pairs are more highly expressed in human blastocysts than other ancestral Z genes. Chicken Z–W pairs n = 26, other ancestral Z genes n = 495, P < 5.4 × 10–5, U = 9,333; 4 species Z–W pairs n = 68, other ancestral Z genes n = 453, P < 0.087, U = 18,156; 14 species Z–W pairs n = 129, other ancestral Z genes n = 392, P < 0.011, U = 28,720.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–3 (PDF 541 kb)

Supplementary Table 1

Tiling path accessions and coordinates. (XLSX 59 kb)

Supplementary Table 2

Ancestral Z genes and associated statistics. (XLSX 295 kb)

Supplementary Table 3

Ancestral ZW pairs from all 14 species. (XLSX 90 kb)

Supplementary Table 4

GO term enrichment. (XLSX 41 kb)

Supplementary Data 1

FASTA sequence of the chicken W chromosome assembly. (TXT 6913 kb)

Supplementary Data 2

FASTA sequence of transcripts of chicken Z–W gene pairs. (TXT 20 kb)

Supplementary Data 3

FASTA-formatted alignment of chicken Z–W gene pairs and human orthologs. (TXT 158 kb)

Supplementary Data 4

Radiation hybrid mapping data. (TXT 175 kb)

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Bellott, D., Skaletsky, H., Cho, TJ. et al. Avian W and mammalian Y chromosomes convergently retained dosage-sensitive regulators. Nat Genet 49, 387–394 (2017). https://doi.org/10.1038/ng.3778

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