Incompatibilities on the sex chromosomes are important in the evolution of hybrid male sterility, but the evolutionary forces underlying this phenomenon are unclear. House mice (Mus musculus) lineages have provided powerful models for understanding the genetic basis of hybrid male sterility. X chromosome–autosome interactions cause strong incompatibilities in M. musculus F1 hybrids, but variation in sterility phenotypes suggests a more complex genetic basis. In addition, XY chromosome conflict has resulted in rapid expansions of ampliconic genes with dosage-dependent expression that is essential to spermatogenesis. Here, we evaluated the contribution of XY lineage mismatch to male fertility and stage-specific gene expression in hybrid mice. We performed backcrosses between two house mouse subspecies to generate reciprocal Y-introgression strains and used these strains to test the effects of XY mismatch in hybrids. Our transcriptome analyses of sorted spermatid cells revealed widespread overexpression of the X chromosome in sterile F1 hybrids independent of Y chromosome subspecies origin. Thus, postmeiotic overexpression of the X chromosome in sterile F1 mouse hybrids is likely a downstream consequence of disrupted meiotic X-inactivation rather than XY gene copy number imbalance. Y chromosome introgression did result in subfertility phenotypes and disrupted expression of several autosomal genes in mice with an otherwise nonhybrid genomic background, suggesting that Y-linked incompatibilities contribute to reproductive barriers, but likely not as a direct consequence of XY conflict. Collectively, these findings suggest that rapid sex chromosome gene family evolution driven by genomic conflict has not resulted in strong male reproductive barriers between these subspecies of house mice.
Rapid Evolution of the Fine-scale Recombination Landscape in Wild House Mouse ( Mus musculus ) Populations
Abstract Meiotic recombination is an important evolutionary force and an essential meiotic process. In many species, recombination events concentrate into hotspots defined by the site-specific binding of PRMD9. Rapid evolution of Prdm9's zinc finger DNA-binding array leads to remarkably abrupt shifts in the genomic distribution of hotspots between species, but the question of how Prdm9 allelic variation shapes the landscape of recombination between populations remains less well understood. Wild house mice (Mus musculus) harbor exceptional Prdm9 diversity, with >150 alleles identified to date, and pose a particularly powerful system for addressing this open question. We employed a coalescent-based approach to construct broad- and fine-scale sex-averaged recombination maps from contemporary patterns of linkage disequilibrium in nine geographically isolated wild house mouse populations, including multiple populations from each of three subspecies. Comparing maps between wild mouse populations and subspecies reveals several themes. First, we report weak fine- and broad-scale recombination map conservation across subspecies and populations, with genetic divergence offering no clear prediction for recombination map divergence. Second, most hotspots are unique to one population, an outcome consistent with minimal sharing of Prdm9 alleles between surveyed populations. Finally, by contrasting aggregate hotspot activity on the X versus autosomes, we uncover evidence for population-specific differences in the degree and direction of sex dimorphism for recombination. Overall, our findings illuminate the variability of both the broad- and fine-scale recombination landscape in M. musculus and underscore the functional impact of Prdm9 allelic variation in wild mouse populations.
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- Award ID(s):
- 1942620
- NSF-PAR ID:
- 10394599
- Editor(s):
- Falush, Daniel
- Date Published:
- Journal Name:
- Molecular Biology and Evolution
- Volume:
- 40
- Issue:
- 1
- ISSN:
- 0737-4038
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Sethuraman, Arun (Ed.)Abstract Recently diverged taxa often exhibit heterogeneous landscapes of genomic differentiation, characterized by regions of elevated differentiation on an otherwise homogeneous background. While divergence peaks are generally interpreted as regions responsible for reproductive isolation, they can also arise due to background selection, selective sweeps unrelated to speciation, and variation in recombination and mutation rates. To investigate the association between patterns of recombination and landscapes of genomic differentiation during the early stages of speciation, we generated fine-scale recombination maps for six southern capuchino seedeaters (Sporophila) and two subspecies of White Wagtail (Motacilla alba), two recent avian radiations in which divergent selection on pigmentation genes has likely generated peaks of differentiation. We compared these recombination maps to those of Collared (Ficedula albicollis) and Pied Flycatchers (Ficedula hypoleuca), non-sister taxa characterized by moderate genomic divergence and a heterogenous landscape of genomic differentiation shaped in part by background selection. Although recombination landscapes were conserved within all three systems, we documented a weaker negative correlation between recombination rate and genomic differentiation in the recent radiations. All divergence peaks between capuchinos, wagtails, and flycatchers were located in regions with lower-than-average recombination rates, and most divergence peaks in capuchinos and flycatchers fell in regions of exceptionally reduced recombination. Thus, co-adapted allelic combinations in these regions may have been protected early in divergence, facilitating rapid diversification. Despite largely conserved recombination landscapes, divergence peaks are specific to each focal comparison in capuchinos, suggesting that regions of elevated differentiation have not been generated by variation in recombination rate alone.more » « less
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Abstract Meiotic recombination landscapes differ greatly between distantly and closely related taxa, populations, individuals, sexes, and even within genomes; however, the factors driving this variation are yet to be well elucidated. Here, we directly estimate contemporary crossover rates and, for the first time, noncrossover rates in rhesus macaques (Macaca mulatta) from four three-generation pedigrees comprising 32 individuals. We further compare these results with historical, demography-aware, linkage disequilibrium–based recombination rate estimates. From paternal meioses in the pedigrees, 165 crossover events with a median resolution of 22.3 kb were observed, corresponding to a male autosomal map length of 2,357 cM—approximately 15% longer than an existing linkage map based on human microsatellite loci. In addition, 85 noncrossover events with a mean tract length of 155 bp were identified—similar to the tract lengths observed in the only other two primates in which noncrossovers have been studied to date, humans and baboons. Consistent with observations in other placental mammals with PRDM9-directed recombination, crossover (and to a lesser extent noncrossover) events in rhesus macaques clustered in intergenic regions and toward the chromosomal ends in males—a pattern in broad agreement with the historical, sex-averaged recombination rate estimates—and evidence of GC-biased gene conversion was observed at noncrossover sites.
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Abstract Meiotic recombination in vertebrates is concentrated in hotspots throughout the genome. The location and stability of hotspots have been linked to the presence or absence of PRDM9, leading to two primary models for hotspot evolution derived from mammals and birds. Species with PRDM9-directed recombination have rapid turnover of hotspots concentrated in intergenic regions (i.e., mammals), whereas hotspots in species lacking PRDM9 are concentrated in functional regions and have greater stability over time (i.e., birds). Snakes possess PRDM9, yet virtually nothing is known about snake recombination. Here, we examine the recombination landscape and test hypotheses about the roles of PRDM9 in rattlesnakes. We find substantial variation in recombination rate within and among snake chromosomes, and positive correlations between recombination rate and gene density, GC content, and genetic diversity. Like mammals, snakes appear to have a functional and active PRDM9, but rather than being directed away from genes, snake hotspots are concentrated in promoters and functional regions—a pattern previously associated only with species that lack a functional PRDM9. Snakes therefore provide a unique example of recombination landscapes in which PRDM9 is functional, yet recombination hotspots are associated with functional genic regions—a combination of features that defy existing paradigms for recombination landscapes in vertebrates. Our findings also provide evidence that high recombination rates are a shared feature of vertebrate microchromosomes. Our results challenge previous assumptions about the adaptive role of PRDM9 and highlight the diversity of recombination landscape features among vertebrate lineages.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/molbev/msac267
