Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes

Abstract

The human X and Y chromosomes evolved from an ordinary pair of autosomes during the past 200–300 million years1,2,3. The human MSY (male-specific region of Y chromosome) retains only three percent of the ancestral autosomes’ genes owing to genetic decay4,5. This evolutionary decay was driven by a series of five ‘stratification’ events. Each event suppressed X–Y crossing over within a chromosome segment or ‘stratum’, incorporated that segment into the MSY and subjected its genes to the erosive forces that attend the absence of crossing over2,6. The last of these events occurred 30 million years ago, 5 million years before the human and Old World monkey lineages diverged. Although speculation abounds regarding ongoing decay and looming extinction of the human Y chromosome7,8,9,10, remarkably little is known about how many MSY genes were lost in the human lineage in the 25 million years that have followed its separation from the Old World monkey lineage. To investigate this question, we sequenced the MSY of the rhesus macaque, an Old World monkey, and compared it to the human MSY. We discovered that during the last 25 million years MSY gene loss in the human lineage was limited to the youngest stratum (stratum 5), which comprises three percent of the human MSY. In the older strata, which collectively comprise the bulk of the human MSY, gene loss evidently ceased more than 25 million years ago. Likewise, the rhesus MSY has not lost any older genes (from strata 1–4) during the past 25 million years, despite its major structural differences to the human MSY. The rhesus MSY is simpler, with few amplified gene families or palindromes that might enable intrachromosomal recombination and repair. We present an empirical reconstruction of human MSY evolution in which each stratum transitioned from rapid, exponential loss of ancestral genes to strict conservation through purifying selection.

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Figure 1: Comparison of rhesus, human and chimpanzee Y chromosomes.
Figure 2: Inventories of genes, both ancestral and added, in rhesus, human and chimpanzee MSYs.
Figure 3: Kinetics of ancestral gene loss during evolution of five human MSY strata.

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Primary accessions

GenBank/EMBL/DDBJ

Data deposits

cDNA sequences of rhesus Y genes have been deposited in GenBank (http://www.ncbi.nlm.nih.gov) under accession numbers FJ527009–FJ527028 and FJ648737–FJ648739. 454 testis cDNA sequences have been deposited in GenBank under accession number SRA039857.

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Acknowledgements

We thank V. Frazzoni, G. Rogers and S. Zaghlul for technical assistance; L. Lyons, W. Murphy and J. Womack for radiation hybrid panels; W. Johnson, E. Curran, S. O’Neil and A. Kaur for tissue samples; R. Harris for analyses of rhesus–human genome alignments; T. DiCesare for assistance with figures; and D. Bellott, M. Carmell, R. Desgraz, Y. Hu, B. Lesch, J. Mueller, K. Romer and S. Soh for comments on the manuscript. This work was supported by the National Institutes of Health, the Howard Hughes Medical Institute and the Charles A. King Trust.

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J.F.H., H.Sk., W.C.W., S.R., R.A.G., R.K.W. and D.C.P. planned the project. J.F.H., H.Sk., L.G.B., T.J.C. and N.K. performed BAC mapping, radiation hybrid mapping and real-time polymerase chain reaction analyses. T.G., R.S.F., S.D., Y.D., C.J.B., C.K., Q.W., H.Sh., M.H., D.V., L.V.N., A.C., L.C., J.V., H.K. and D.M.M. were responsible for BAC sequencing. J.F.H. and H.Sk. performed comparative sequence analyses. T.P. performed FISH analyses. J.F.H. and D.C.P. wrote the paper.

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Correspondence to Jennifer F. Hughes.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Notes 1-3, Supplementary Figures 1-16 with legends and Supplementary Tables 1-8. (PDF 16750 kb)

Supplementary Data 1

This is a FASTA file of rhesus MSY sequence assembly. (TXT 11806 kb)

Supplementary Data 2

This file contains radiation hybrid mapping data vectors. (TXT 1 kb)

Supplementary Data 3

This file shows the alignment of rhesus and human MSY sequences in FASTA format. (TXT 9279 kb)

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Hughes, J., Skaletsky, H., Brown, L. et al. Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes. Nature 483, 82–86 (2012). https://doi.org/10.1038/nature10843

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