Studies of a hybrid zone between two house mouse subspecies (Mus musculus musculus and M. m. domesticus) along with studies using laboratory crosses reveal a large role for the X chromosome and multiple autosomal regions in reproductive isolation as a consequence of disrupted epistasis in hybrids. One limitation of previous work has been that most of the identified genomic regions have been large. The goal here is to detect and characterize precise genomic regions underlying reproductive isolation. We surveyed 1401 markers evenly spaced across the genome in 679 mice collected from two different transects. Comparisons between transects provide a means for identifying common patterns that likely reflect intrinsic incompatibilities. We used a genomic cline approach to identify patterns that correspond to epistasis. From both transects, we identified contiguous regions on the X chromosome in which markers were inferred to be involved in epistatic interactions. We then searched for autosomal regions showing the same patterns and found they constitute about 5% of autosomal markers. We discovered substantial overlap between these candidate regions underlying reproductive isolation and QTL for hybrid sterility identified in laboratory crosses. Analysis of gene content in these regions suggests a key role for several mechanisms, including the regulation of transcription, sexual conflict and sexual selection operating at both the postmating prezygotic and postzygotic stages of reproductive isolation. Taken together, these results indicate that speciation in two recently diverged (c. 0.5 Ma) house mouse subspecies is complex, involving many genes dispersed throughout the genome and associated with distinct functions.

Department of Zoology Faculty of Science Charles University Prague Viničná 7 128 43 Prague 2 Czech Republic

Zobrazit více v PubMed

Ashburner M, Ball CA, Blake JA, et al. Gene ontology: tool for the unification of biology. Nature Genetics. 2000;25:25–29. PubMed PMC

Baird SJE, Macholán M. What can the Mus musculus musculus/M. m. domesticus hybrid zone tell us about speciation? In: Macholán M, Baird SJE, Munclinger P, Piálek J, editors. Evolution of the House Mouse. Cambridge Studies in Morphology and Molecules. New Paradigms in Evolutionary Biology. Cambridge University Press; Cambridge, UK: 2012. in press.

Baird SJE, Ribas A, Macholán M, et al. Where are the wormy mice? A re-examination of hybrid parasitism in the European house mouse hybrid zon. Evolution. 2012 doi: 10.1111/j.1558-5646.2012.01633.x. PubMed

Barton NH. Dynamics of hybrid zones. Heredity. 1979;43:341–359.

Barton NH. Multilocus clines. Evolution. 1983;37:454–471. PubMed

Barton NH, Charlesworth B. Genetic revolutions, founder effects, and speciation. Annual Review of Ecology and Systematics. 1984;15:133–164.

Barton NH, Gale KS. Genetic analysis of hybrid zones. In: Harrison RG, editor. Hybrid Zones and the Evolutionary Process. Oxford University Press; Oxford, UK: 1993. pp. 13–45.

Barton NH, Hewitt GM. Analysis of hybrid zones. Annual Review of Ecology and Systematics. 1985;16:113–148.

Bateson W. Heredity and variation in modern lights. In: Seward AC, editor. Darwin and Modern Science. University Press; Cambridge, UK: 1909. pp. 85–101.

Boursot P, Belkhir K. Mouse SNPs for evolutionary biology: beware of ascertainment biases. Genome Research. 2006;16:1191–1192. PubMed

Boursot P, Auffray JC, Britton-Davidian J, Bonhomme F. The evolution of house mice. Annual Review of Ecology and Systematics. 1993;24:119–152.

Boursot P, Din W, Anand R, et al. Origin and radiation of the house mouse: mitochondrial DNA phylogeny. Journal of Evolutionary Biology. 1996;9:391–415.

Boyle EI, Weng S, Gollub J, et al. GO::TermFinder – open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes. Bioinformatics. 2004;20:3710–3715. PubMed PMC

Božíková E, Munclinger P, Teeter KC, Tucker PK, Macholán M, Piálek J. Mitochondrial DNA in the hybrid zone between Mus musculus musculus and Mus musculus domesticus: a comparison of two transects. Biological Journal of the Linnean Society. 2005;84:363–378.

Britton-Davidian J, Fel-Clair F, Lopez J, Alibert P, Boursot P. Postzygotic isolation between the two European subspecies of the house mouse: estimates from fertility patterns in wild and laboratory-bred hybrids. Biological Journal of the Linnean Society. 2005;84:379–393.

Buerkle CA. Maximum-likelihood estimation of a hybrid index based on molecular markers. Molecular Ecology Notes. 2005;5:684–687.

Buerkle CA, Lexer C. Admixture as the basis for genetic mapping. Trends in Ecology and Evolution. 2008;23:686–694. PubMed

Charlesworth B, Coyne JA, Barton NH. The relative rates of evolution of sex-chromosomes and autosomes. American Naturalist. 1987;130:113–146.

Cheetham SA, Thom MD, Jury F, Ollier WER, Beynon RJ, Hurst JL. The genetic basis of individual-recognition signals in the mouse. Current Biology. 2007;17:1771–1777. PubMed

Chevret P, Veyrunes F, Britton-Davidian J. Molecular phylogeny of the genus Mus (Rodentia: Murinae) based on mitochondrial and nuclear data. Biological Journal of the Linnean Society. 2005;84:417–427.

Clark NL, Aagaard JE, Swanson WJ. Evolution of reproductive proteins from animals and plants. Reproduction. 2006;131:11–22. PubMed

Coyne JA, Orr HA. Patterns of speciation in Drosophila. Evolution. 1989;43:362–381. PubMed

Coyne JA, Orr HA. Speciation. Sinauer Associates, Inc.; Sunderland, Massachusetts: 2004.

Dean MD, Nachman MW. Faster fertilization rate in conspecific versus heterospecific matings in house mice. Evolution. 2009;63:20–28. PubMed PMC

Dean MD, Ardlie KG, Nachman MW. The frequency of multiple paternity suggests that sperm competition is common in house mice (Mus domesticus) Molecular Ecology. 2006;15:4141–4151. PubMed PMC

Dean MD, Good JM, Nachman MW. Adaptive evolution of proteins secreted during sperm maturation: an analysis of the mouse epididymal transcriptome. Molecular Biology and Evolution. 2008;25:383–392. PubMed PMC

Dean MD, Clark NL, Findlay GD, et al. Proteomics and comparative genomic investigations reveal heterogeneity in evolutionary rate of male reproductive proteins in mice (Mus domesticus) Molecular Biology and Evolution. 2009;26:1733–1743. PubMed PMC

Dean MD, Findlay GD, Hoopmann MR, et al. Identification of ejaculated proteins in the house mouse (Mus domesticus) via isotopic labeling. BMC Genomics. 2011;12:306. PubMed PMC

Dobzhansky T. Studies on hybrid sterility. 11. Localization of sterility factors in Drosophila pseudoobscura hybrids. Genetics. 1936;21:113–135. PubMed PMC

Dobzhansky T. Genetics and the Origin of Species. Columbia University Press, New York; New York: 1937.

Dod B, Jermiin LS, Boursot P, Chapman VH, Nielsen JT, Bonhomme F. Counterselection on sex-chromosomes in the Mus musculus European hybrid zone. Journal of Evolutionary Biology. 1993;6:529–546.

Dorus S, Wasbrough ER, Busby J, Wilkin EC, Karr TL. Sperm proteomics reveals intensified selection on mouse sperm membrane and acrosome genes. Molecular Biology and Evolution. 2010;27:1235–1246. PubMed PMC

Dufková P, Macholán M, Piálek J. Inference of selection and stochastic effects in the house mouse hybrid zone. Evolution. 2011;65:993–1010. PubMed

Duvaux L, Belkhir K, Boulesteix M, Boursot P. Isolation and gene flow: inferring the speciation history of European house mice. Molecular Ecology. 2011;20:5248–5264. PubMed

Forejt J. Hybrid sterility in the mouse. Trends in Genetics. 1996;12:412–417. PubMed

Forejt J, Iványi P. Genetic studies on male-sterility of hybrids between laboratory and wild mice (Mus musculus) Genetical Research. 1974;24:189–206. PubMed

Ganem G, Litel C, Lenormand T. Variation in mate preference across a house mouse hybrid zone. Heredity. 2008;100:594–601. PubMed

Geraldes A, Basset P, Gibson B, et al. Inferring the history of speciation in house mice from autosomal, X-linked, Y-linked and mitochondrial genes. Molecular Ecology. 2008;17:5349–5363. PubMed PMC

Geraldes A, Basset P, Smith KL, Nachman MW. Higher differentiation among subspecies of the house mouse (Mus musculus) in genomic regions with low recombination. Molecular Ecology. 2011;20:4722–4736. PubMed PMC

Gompert Z, Buerkle CA. A powerful regression-based method for admixture mapping of isolation across the genome of hybrids. Molecular Ecology. 2009;18:1207–1224. PubMed

Gompert Z, Buerkle CA. INTROGRESS: a software package for mapping components of isolation in hybrids. Molecular Ecology Resources. 2010;10:378–384. PubMed

Gompert Z, Buerkle CA. Bayesian estimation of genomic clines. Molecular Ecology. 2011;20:2111–2127. PubMed

Good JM, Handel MA, Nachman MW. Asymmetry and polymorphism of hybrid male sterility during the early stages of speciation in house mice. Evolution. 2008a;62:50–65. PubMed PMC

Good JM, Dean MD, Nachman MW. A complex genetic basis to X-linked hybrid male sterility between two species of house mice. Genetics. 2008b;179:2213–2228. PubMed PMC

Good JM, Giger T, Dean MD, Nachman MW. Widespread over-expression of the X chromosome in sterile F1 hybrid mice. PLoS Genetics. 2010;6:e1001148. PubMed PMC

Good JM, Vanderpool D, Smith KL, Nachman MW. Extraordinary sequence divergence at Tsga8, an X-linked gene involved in mouse spermiogenesis. Molecular Biology and Evolution. 2011;28:1675–1686. PubMed PMC

Gouy de Bellocq J, Ribas A, Baird SJE. New insights into parasitism in the house mouse hybrid zone. In: Macholán M, Baird SJE, Munclinger P, Piálek J, editors. Evolution of the House Mouse. Cambridge Studies in Morphology and Molecules. New Paradigms in Evolutionary Biology. Cambridge University Press; Cambridge, UK: 2012. In press.

Gregorová S, Divina P, Storchová R, et al. Mouse consomic strains: exploiting genetic divergence between Mus m. musculus and Mus m. domesticus subspecies. Genome Research. 2008;18:509–515. PubMed PMC

Haldane JBS. Sex ratio and unisexual sterility in hybrid animals. Journal of Genetics. 1922;12:101–109.

Harr B. Genomic islands of differentiation between house mouse subspecies. Genome Research. 2006;16:730–737. PubMed PMC

Jones EP, Van der Kooij J, Solheim R, Searle JB. Norwegian house mice (Mus musculus musculus/domesticus): distributions, routes of colonization and patterns of hybridization. Molecular Ecology. 2010;19:5252–5264. PubMed

Karn RC, Dlouhy SR. Salivary androgen-binding protein variation in Mus and other rodents. Journal of Heredity. 1991;82:453–458. PubMed

Laukaitis CM, Critser ES, Karn RC. Salivary androgenbinding protein (ABP) mediates sexual isolation in Mus musculus. Evolution. 1997;51:2000–2005. PubMed

Lu X, Shapiro JA, Ting CT, et al. Genome-wide misexpression of X-linked versus autosomal genes associated with hybrid male sterility. Genome Research. 2010;20:1097–1102. PubMed PMC

Macholán M, Kryštůfek B, Vohralík V. The location of the Mus musculus/M. domesticus hybrid zone in the Balkans clues from morphology. Acta Theriologica. 2003;48:177–188.

Macholán M, Munclinger P, Sugerková M, et al. Genetic analysis of autosomal and X-linked markers across a mouse hybrid zone. Evolution. 2007;61:746–771. PubMed

Macholán M, Baird S, Munclinger P, Dufková P, Bímová B, Piálek J. Genetic conflict outweighs heterogametic incompatibility in the mouse hybrid zone? BMC Evolutionary Biology. 2008;8:271. PubMed PMC

Macholán M, Baird SJE, Dufková P, Munclinger P, Vošlajerová Bímová B, Piálek J. Assessing multilocus introgression patterns: a case study on the mouse X chromosome in central Europe. Evolution. 2011;65:1428–1446. PubMed

Masly JP, Presgraves DC. High-resolution genome-wide dissection of the two rules of speciation in Drosophila. PLoS Biology. 2007;5:1890–1898. PubMed PMC

Mayr E. Systematics and the Origin of Species. Columbia University Press, New York; New York: 1942.

Mihola O, Trachtulec Z, Vlček C, Schimenti JC, Forejt J. A mouse speciation gene encodes a meiotic histone H3 methyltransferase. Science. 2009;323:373–375. PubMed

Moulia C, Lebrun N, Dallas J, Orth A, Renaud F. Experimental-evidence of genetic determinism in high susceptibility to intestinal pinworm infection in mice – a hybrid zone model. Parasitology. 1993;106:387–393. PubMed

Muller HJ. Bearing of the Drosophila work on systematics. In: Huxley JS, editor. The New Systematics. Clarendon Press, Oxford; UK: 1940. pp. 185–268.

Muller HJ. Isolating mechanisms, evolution, and temperature. Biological Symposium. 1942;6:71–125.

Nagylaki T. Conditions for existence of clines. Genetics. 1975;80:595–615. PubMed PMC

Nosil P, Funk DJ, Ortiz-Barrientos D. Divergent selection and heterogeneous genomic divergence. Molecular Ecology. 2009;18:375–402. PubMed

Oka A, Mita A, Sakurai-Yamatani N, et al. Hybrid breakdown caused by substitution of the X chromosome between two mouse subspecies. Genetics. 2004;166:913–924. PubMed PMC

Oka A, Aoto T, Totsuka Y, et al. Disruption of genetic interaction between two autosomal regions and the X chromosome causes reproductive isolation between mouse strains derived from different subspecies. Genetics. 2007;175:185–197. PubMed PMC

Orr HA. Haldane’s rule. Annual Review of Ecology and Systematics. 1997;28:195–218. PubMed

Orr HA, Irving S. Complex epistasis and the genetic basis of hybrid sterility in the Drosophila pseudoobscura Bogota-USA hybridization. Genetics. 2001;158:1089–1100. PubMed PMC

Payseur BA. Using differential introgression in hybrid zones to identify genomic regions involved in speciation. Molecular Ecology Resources. 2010;10:806–820. PubMed

Payseur BA, Krenz JG, Nachman MW. Differential patterns of introgression across the X chromosome in a hybrid zone between two species of house mice. Evolution. 2004;58:2064–2078. PubMed

Polechová J, Barton NH. Genetic drift widens the expected cline but narrows the expected cline width. Genetics. 2011;189:227–235. PubMed PMC

Presgraves DC. Sex chromosomes and speciation in Drosophila. Trends in Genetics. 2008;24:336–343. PubMed PMC

R Development Core Team . R: A Language and Environment for Statistical Computing, Reference Index Version 2.13.1. R Foundation for Statistical Computing, Vienna; Austria: 2005. ISBN 3-900051-07-0. http://www.R-project.org.

Raufaste N, Orth A, Belkhir K, et al. Inferences of selection and migration in the Danish house mouse hybrid zone. Biological Journal of the Linnean Society. 2005;84:593–616.

Rieseberg LH, Buerkle CA. Genetic mapping in hybrid zones. American Naturalist. 2002;159:S36–S50. PubMed

Sage RD, Heyneman D, Lim KC, Wilson AC. Wormy mice in a hybrid zone. Nature. 1986;324:60–63. PubMed

Salcedo T, Geraldes A, Nachman MW. Nucleotide variation in wild and inbred mice. Genetics. 2007;177:2277–2291. PubMed PMC

Shin JH, Blay S, McNeney B, Graham J. LDheatmap: an R function for graphical display of pairwise linkage disequilibria between single nucleotide polymorphisms. Journal of Statistical Software. 2006;16 http://www.jstatsoft.org/v16/c03/paper.

Smadja C, Ganem G. Subspecies recognition in the house mouse: a study of two populations from the border of a hybrid zone. Behavioral Ecology. 2002;13:312–320.

Smadja C, Ganem G. Asymmetrical reproductive character displacement in the house mouse. Journal of Evolutionary Biology. 2005;18:1485–1493. PubMed

Smadja C, Ganem G. Divergence of odorant signals within and between the two European subspecies of the house mouse. Behavioral Ecology. 2008;19:223–230.

Smadja C, Catalan J, Ganem G. Strong premating divergence in a unimodal hybrid zone between two subspecies in the house mouse. Journal of Evolutionary Biology. 2004;17:165–176. PubMed

Stopková R, Stopka R, Janotová K, Jedelský P. Speciesspecific expression of major urinary proteins in the house mice (Mus musculus musculus and Mus musculus domesticus) Journal of Chemical Ecology. 2007;33:861–869. PubMed

Storchová R, Gregorová S, Buckiová D, Kyselová V, Divina P, Forejt J. Genetic analysis of X-linked hybrid sterility in the house mouse. Mammalian Genome. 2004;15:515–524. PubMed

Storey JD, Tibshirani R. Statistical significance for genomewide studies. PNAS. 2003;100:9440–9445. PubMed PMC

Suzuki H, Shimada T, Terashima M, Tsuchiya K, Aplin K. Temporal, spatial, and ecological modes of evolution of Eurasian Mus based on mitochondrial and nuclear gene sequences. Molecular Phylogenetics and Evolution. 2004;33:626–646. PubMed

Talley HM, Laukaitis CM, Karn RC. Female preference for male saliva: implications for sexual isolation of Mus musculus subspecies. Evolution. 2001;55:631–634. PubMed

Tao Y, Chen S, Hartl DL, Laurie CC. Genetic dissection of hybrid incompatibilities between Drosophila simulans and Drosophila mauritiana. I. Differential accumulation of hybrid male sterility effects on the X and autosomes. Genetics. 2003;164:1383–1397. PubMed PMC

Teeter KC, Payseur BA, Harris LW, et al. Genome-wide patterns of gene flow across a house mouse hybrid zone. Genome Research. 2008;18:67–76. PubMed PMC

Thom MD, Stockley P, Jury F, Ollier WER, Beynon RJ, Hurst JL. The direct assessment of genetic heterozygosity through scent in the mouse. Current Biology. 2008;18:619–623. PubMed

True JR, Weir BS, Laurie CC. A genome-wide survey of hybrid incompatibility factors by the introgression of marked segments of Drosophila mauritiana chromosomes into Drosophila simulans. Genetics. 1996;142:819–837. PubMed PMC

Tucker PK, Sage RD, Warner J, Wilson AC, Eicher EM. Abrupt cline for sex-chromosomes in a hybrid zone between two species of mice. Evolution. 1992;46:1146–1163. PubMed

Turelli M, Orr HA. The dominance theory of Haldane’s rule. Genetics. 1995;140:389–402. PubMed PMC

Turner LM, Schwahn DJ, Harr B. Reduced male fertility is common but highly variable in form and severity in a natural house mouse hybrid zone. Evolution. 2012;66:443–458. in press. PubMed

Vošlajerová Bímová B, Macholán M, Baird SJE, et al. Reinforcement selection acting on the European house mouse hybrid zone. Molecular Ecology. 2011;20:2403–2424. PubMed

Vyskočilová M, Trachtulec Z, Forejt J, Piálek J. Does geography matter in hybrid sterility in house mice? Biological Journal of the Linnean Society. 2005;84:663–674.

Vyskočilová M, Prazanova G, Piálek J. Polymorphism in hybrid male sterility in wild-derived Mus musculus musculus strains on proximal chromosome 17. Mammalian Genome. 2009;20:83–91. PubMed

Wang L, Luzynski K, Pool JE, et al. Measures of linkage disequilibrium among neighbouring SNPs indicate asymmetries across the house mouse hybrid zone. Molecular Ecology. 2011;20:2985–3000. PubMed

White MA, Steffy B, Wiltshire T, Payseur BA. Genetic dissection of a key reproductive barrier between nascent species of house mice. Genetics. 2011;189:289–304. PubMed PMC

Yang H, Ding Y, Hutchins LN, et al. A customized and versatile high-density genotyping array for the mouse. Nature Methods. 2009;6:663–666. PubMed PMC

Yang HN, Wang JR, Didion JP, et al. Subspecific origin and haplotype diversity in the laboratory mouse. Nature Genetics. 2011;43:648–655. PubMed PMC

Zeng LW. Resurrecting Muller’s theory of Haldane’s rule. Genetics. 1996;143:603–607. PubMed PMC

Synthesis and Scope of the Role of Postmating Prezygotic Isolation in Speciation

Meiotic Recognition of Evolutionarily Diverged Homologs: Chromosomal Hybrid Sterility Revisited

Genic and chromosomal components of Prdm9-driven hybrid male sterility in mice (Mus musculus)

Sex chromosomes in meiotic, hemiclonal, clonal and polyploid hybrid vertebrates: along the 'extended speciation continuum'

Do all mice smell the same? Chemosensory cues from inbred and wild mouse strains elicit stereotypic sensory representations in the accessory olfactory bulb

Wolbachia affects mitochondrial population structure in two systems of closely related Palaearctic blue butterflies

Prdm9 Intersubspecific Interactions in Hybrid Male Sterility of House Mouse

Genomic Structure of Hstx2 Modifier of Prdm9-Dependent Hybrid Male Sterility in Mice

Phenotypic effects of the Y chromosome are variable and structured in hybrids among house mouse recombinant lines

Empirical evidence for large X-effects in animals with undifferentiated sex chromosomes

Functional organization of the genome may shape the species boundary in the house mouse

Prdm9 incompatibility controls oligospermia and delayed fertility but no selfish transmission in mouse intersubspecific hybrids

X chromosome control of meiotic chromosome synapsis in mouse inter-subspecific hybrids

Coevolution of Cryptosporidium tyzzeri and the house mouse (Mus musculus)

Mechanistic basis of infertility of mouse intersubspecific hybrids

Sperm-related phenotypes implicated in both maintenance and breakdown of a natural species barrier in the house mouse