WTAF?!
Genomic Networks of Hybrid Sterility
Leslie M. Turner ,
Michael A. White,
Diethard Tautz,
Bret A. Payseur
https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004162
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.
Author Summary
New species are created when barriers to reproduction form between groups of organisms that formerly interbred freely. Reduced fertility or viability of hybrid offspring is a common form of reproductive isolation. Hybrid defects are caused by negative interactions between genes that have undergone evolutionary change within each subgroup. Identifying genetic interactions causing disease or trait variation is very difficult, consequently there are few known hybrid incompatibility genes and even fewer cases where both interacting genes are known. Here, we combined mapping of gene expression levels in testis with previous results mapping male sterility traits in hybrid house mice. This new approach to finding genetic causes of reproductive barriers enabled us to identify a large number of hybrid incompatibilities, involving genomic regions with known roles in hybrid sterility and previously unknown regions. Understanding the number and type of genetic interactions is important for developing accurate models used to reconstruct speciation events. The genetics of hybrid sterility in mice may also contribute to understanding basic processes involved in male reproduction and causes of human infertility.
Remind me again what that instrumental song in the BG of one of the Q posted vids was titled?
Something about hybridization of humanity, yes?