Hybrid incompatibilities are observed among the offspring of crosses between closely related plant and animal species. They are known as causing sterility and lethality in one or both sexes, usually the heterogametic sex (XY males or ZW females) and are important evolutionarily because they act as reproductive barriers that can both promote speciation in sympatric populations and maintain the integrity of the species following allopatric divergence. A familiar example of hybrid sterility is observed in male mules, which bear one set of chromosomes from a horse mother and another from a donkey father. Genomic incompatibilities are numerous, and typically distributed across all chromosomes, yet we know little about the nature of the genes underlying hybrid sterility.
In the latter case, it is very likely that the incompatibilities have evolved long after the initial establishment of reproductive isolation. Following the Dobzhansky-Müller model, genetic changes accumulate naturally in diverging populations (parental species), and the incompatibilities are revealed only in the unique genetic background of hybrid between two species. Genetic incompatibilities between well-established species are typically the result of numerous genetic factors, and each incompatibility factor is complex: it can harbor one or several loci each and result from deleterious interactions between nucleotide sites in different regions of a gene and with other interacting genes or encoded proteins.
To address this fundamental question, I worked with two species of fruitfly (Drosophila simulans and D. mauritiana), which is a well-established model organism with only four pairs of chromosomes, a short life cycle and powerful research resources. Using a system in which small pieces of the D. mauritiana genome have been introduced by repeated crossing (introgression) into D. simulans allows to study each region individually, in order to ask what are the genes from D. mauritiana that are incompatible in the D. simulans genetic background.
Figure legend: HMS1 structure and phenotype. (A) Genetic map of HMS1 region showing location of P32 and P45 P-element insertions as well as the extent of D. mauritiana Mau12 genome present in the P32.110 and P45.6 introgressions obtained by repeated backcrossing. P-elements P45 and P32 localize to polytene bands 83A and 84E8, respectively. (B) Expanded map of HMS1 region showing the genes in and near the region. (C) The phenotype of the HMS1[mau]/HMS1[mau] homozygous males showing that the great majority of males are completely sterile, whereas only a few are quasi sterile; the phenotype of the HMS1 [mau]/HMS1[sim] heterozygous males is complete fertility rescue with high numbers of progeny among most of the fertile males. Liénard et al. PNAS 2016.
By investigating in detail a hybrid sterility factor called HMS1, I recently demonstrated that a small region on chromosome 3 in D. mauritiana contains two neighboring genes that each contribute to sterility when introgressed into the genome of D. simulans, due to multiple nucleotide differences between the two species. Each gene causes about half of the sterility, underlying reproductive isolation as a Polygenic Quantitative Trait. Read More.