Genomic networks of hybrid sterility

Leslie M. Turner, Michael A. White, Diethard Tautz, Bret A. Payseur

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Hybrid dysfunction, a common feature of reproductive barriers between species, is often caused by negative epistasis between loci ("Dobzhansky-Muller incompatibilities"). The nature and complexity of hybrid incompatibilities remain poorly understood because identifying interacting loci that affect complex phenotypes is difficult. With subspecies in the early stages of speciation, an array of genetic tools, and detailed knowledge of reproductive biology, house mice (Mus musculus) provide a model system for dissecting hybrid incompatibilities. Male hybrids between M. musculus subspecies often show reduced fertility. Previous studies identified loci and several X chromosome-autosome interactions that contribute to sterility. To characterize the genetic basis of hybrid sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven 'hotspots,' seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL-but not cis eQTL-were substantially lower when mapping was restricted to a 'fertile' subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility. The integrated mapping approach we employed is applicable in a broad range of organisms and we advocate for widespread adoption of a network-centered approach in speciation genetics.

Original languageEnglish
Article numbere1004162
JournalPlos Genetics
Volume10
Issue number2
DOIs
Publication statusPublished - 20 Feb 2014

Fingerprint

sterility
Infertility
genomics
Mus musculus
loci
incompatibility
Genetic Speciation
quantitative trait loci
epistasis
phenotype
X chromosome
X Chromosome
Phenotype
subspecies
chromosome
prioritization
autosomes
Biological Phenomena
reproductive biology
testes

Keywords

  • Animals
  • Crosses, Genetic
  • Genetic Speciation
  • Genomics
  • Hybridization, Genetic
  • Infertility, Male
  • Male
  • Mice
  • Quantitative Trait Loci
  • Reproduction
  • Reproductive Isolation
  • X Chromosome
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

Turner, L. M., White, M. A., Tautz, D., & Payseur, B. A. (2014). Genomic networks of hybrid sterility. Plos Genetics, 10(2), [e1004162]. https://doi.org/10.1371/journal.pgen.1004162

Genomic networks of hybrid sterility. / Turner, Leslie M.; White, Michael A.; Tautz, Diethard; Payseur, Bret A.

In: Plos Genetics, Vol. 10, No. 2, e1004162, 20.02.2014.

Research output: Contribution to journalArticle

Turner, LM, White, MA, Tautz, D & Payseur, BA 2014, 'Genomic networks of hybrid sterility', Plos Genetics, vol. 10, no. 2, e1004162. https://doi.org/10.1371/journal.pgen.1004162
Turner, Leslie M. ; White, Michael A. ; Tautz, Diethard ; Payseur, Bret A. / Genomic networks of hybrid sterility. In: Plos Genetics. 2014 ; Vol. 10, No. 2.
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AB - Hybrid dysfunction, a common feature of reproductive barriers between species, is often caused by negative epistasis between loci ("Dobzhansky-Muller incompatibilities"). The nature and complexity of hybrid incompatibilities remain poorly understood because identifying interacting loci that affect complex phenotypes is difficult. With subspecies in the early stages of speciation, an array of genetic tools, and detailed knowledge of reproductive biology, house mice (Mus musculus) provide a model system for dissecting hybrid incompatibilities. Male hybrids between M. musculus subspecies often show reduced fertility. Previous studies identified loci and several X chromosome-autosome interactions that contribute to sterility. To characterize the genetic basis of hybrid sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven 'hotspots,' seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL-but not cis eQTL-were substantially lower when mapping was restricted to a 'fertile' subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility. The integrated mapping approach we employed is applicable in a broad range of organisms and we advocate for widespread adoption of a network-centered approach in speciation genetics.

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