Recombination hotspots in an extended human pseudoautosomal domain predicted from double-strand break maps and characterized by sperm-based crossover analysis
© 2018 Poriswanish et al. http://creativecommons.org/licenses/by/4.0/. The human X and Y chromosomes are heteromorphic but share a region of homology at the tips of their short arms, pseudoautosomal region 1 (PAR1), that supports obligate crossover in male meiosis. Although the boundary between pseu...
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th-mahidol.446722019-08-23T18:42:09Z Recombination hotspots in an extended human pseudoautosomal domain predicted from double-strand break maps and characterized by sperm-based crossover analysis Nitikorn Poriswanish Rita Neumann Jon H. Wetton John Wagstaff Maarten H.D. Larmuseau Mark A. Jobling Celia A. May University of Leicester KU Leuven Faculty of Medicine, Siriraj Hospital, Mahidol University Agricultural and Biological Sciences Biochemistry, Genetics and Molecular Biology Medicine © 2018 Poriswanish et al. http://creativecommons.org/licenses/by/4.0/. The human X and Y chromosomes are heteromorphic but share a region of homology at the tips of their short arms, pseudoautosomal region 1 (PAR1), that supports obligate crossover in male meiosis. Although the boundary between pseudoautosomal and sex-specific DNA has traditionally been regarded as conserved among primates, it was recently discovered that the boundary position varies among human males, due to a translocation of ~110 kb from the X to the Y chromosome that creates an extended PAR1 (ePAR). This event has occurred at least twice in human evolution. So far, only limited evidence has been presented to suggest this extension is recombinationally active. Here, we sought direct proof by examining thousands of gametes from each of two ePAR-carrying men, for two subregions chosen on the basis of previously published male X-chromosomal meiotic double-strand break (DSB) maps. Crossover activity comparable to that seen at autosomal hotspots was observed between the X and the ePAR borne on the Y chromosome both at a distal and a proximal site within the 110-kb extension. Other hallmarks of classic recombination hotspots included evidence of transmission distortion and GC-biased gene conversion. We observed good correspondence between the male DSB clusters and historical recombination activity of this region in the X chromosomes of females, as ascertained from linkage disequilibrium analysis; this suggests that this region is similarly primed for crossover in both male and female germlines, although sex-specific differences may also exist. Extensive resequencing and inference of ePAR haplotypes, placed in the framework of the Y phylogeny as ascertained by both Y microsatellites and single nucleotide polymorphisms, allowed us to estimate a minimum rate of crossover over the entire ePAR region of 6-fold greater than genome average, comparable with pedigree estimates of PAR1 activity generally. We conclude ePAR very likely contributes to the critical crossover function of PAR1. 2019-08-23T10:14:14Z 2019-08-23T10:14:14Z 2018-10-01 Article PLoS Genetics. Vol.14, No.10 (2018) 10.1371/journal.pgen.1007680 15537404 15537390 2-s2.0-85055166013 https://repository.li.mahidol.ac.th/handle/123456789/44672 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85055166013&origin=inward |
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Agricultural and Biological Sciences Biochemistry, Genetics and Molecular Biology Medicine Nitikorn Poriswanish Rita Neumann Jon H. Wetton John Wagstaff Maarten H.D. Larmuseau Mark A. Jobling Celia A. May Recombination hotspots in an extended human pseudoautosomal domain predicted from double-strand break maps and characterized by sperm-based crossover analysis |
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© 2018 Poriswanish et al. http://creativecommons.org/licenses/by/4.0/. The human X and Y chromosomes are heteromorphic but share a region of homology at the tips of their short arms, pseudoautosomal region 1 (PAR1), that supports obligate crossover in male meiosis. Although the boundary between pseudoautosomal and sex-specific DNA has traditionally been regarded as conserved among primates, it was recently discovered that the boundary position varies among human males, due to a translocation of ~110 kb from the X to the Y chromosome that creates an extended PAR1 (ePAR). This event has occurred at least twice in human evolution. So far, only limited evidence has been presented to suggest this extension is recombinationally active. Here, we sought direct proof by examining thousands of gametes from each of two ePAR-carrying men, for two subregions chosen on the basis of previously published male X-chromosomal meiotic double-strand break (DSB) maps. Crossover activity comparable to that seen at autosomal hotspots was observed between the X and the ePAR borne on the Y chromosome both at a distal and a proximal site within the 110-kb extension. Other hallmarks of classic recombination hotspots included evidence of transmission distortion and GC-biased gene conversion. We observed good correspondence between the male DSB clusters and historical recombination activity of this region in the X chromosomes of females, as ascertained from linkage disequilibrium analysis; this suggests that this region is similarly primed for crossover in both male and female germlines, although sex-specific differences may also exist. Extensive resequencing and inference of ePAR haplotypes, placed in the framework of the Y phylogeny as ascertained by both Y microsatellites and single nucleotide polymorphisms, allowed us to estimate a minimum rate of crossover over the entire ePAR region of 6-fold greater than genome average, comparable with pedigree estimates of PAR1 activity generally. We conclude ePAR very likely contributes to the critical crossover function of PAR1. |
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University of Leicester |
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University of Leicester Nitikorn Poriswanish Rita Neumann Jon H. Wetton John Wagstaff Maarten H.D. Larmuseau Mark A. Jobling Celia A. May |
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Article |
author |
Nitikorn Poriswanish Rita Neumann Jon H. Wetton John Wagstaff Maarten H.D. Larmuseau Mark A. Jobling Celia A. May |
author_sort |
Nitikorn Poriswanish |
title |
Recombination hotspots in an extended human pseudoautosomal domain predicted from double-strand break maps and characterized by sperm-based crossover analysis |
title_short |
Recombination hotspots in an extended human pseudoautosomal domain predicted from double-strand break maps and characterized by sperm-based crossover analysis |
title_full |
Recombination hotspots in an extended human pseudoautosomal domain predicted from double-strand break maps and characterized by sperm-based crossover analysis |
title_fullStr |
Recombination hotspots in an extended human pseudoautosomal domain predicted from double-strand break maps and characterized by sperm-based crossover analysis |
title_full_unstemmed |
Recombination hotspots in an extended human pseudoautosomal domain predicted from double-strand break maps and characterized by sperm-based crossover analysis |
title_sort |
recombination hotspots in an extended human pseudoautosomal domain predicted from double-strand break maps and characterized by sperm-based crossover analysis |
publishDate |
2019 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/44672 |
_version_ |
1763488685229080576 |