Finding Genomic Hybrid Incompatibilities Between Members of the Anopheles gambiae Complex

The Batson-Dobzhasnky-Muller model predicts that as species diverge over time they will accumulate genetic differences, which may be incompatible with each other when combined into the same genetic background. Despite the central importance of this process to diversification and speciation, identification of genes causing hybrid dysfunction have been limited primarily to model species. Anopheles gambiae, the principal mosquito vector of malaria in Africa, belongs to a complex of at least nine isomorphic species. In accordance with Haldane’s rule, reciprocal crosses between members of the Anopheles gambiae complex resulted in completely sterile males, a fact that was used to classify different mosquito populations into separate species. Some of these hybrid crosses were also found to have sex-ratio distortion implying some form of female hybrid inviability, refuting Haldane’s rule. Those females that were viable were also found to be fertile. Using reciprocal crosses between An. coluzzii and An. merus we found that when F1 hybrid females were backcrossed, the resulting male progeny displayed a range of phenotypes from completely sterile to completely fertile providing the foundation for quantitative trait locus (QTL) mapping. We performed reciprocal backcrosses, phenotyped ~2500 males from those backcrosses, and are in the process of genotyping each individual male at an average of >10,000 markers across the genome using a reduced representation sequencing approach. By doing RNA-seq on F1 hybrid testes we also found evidence of disruption of sex chromosome inactivation in one of our crosses, an under-appreciated mechanism of Haldane’s rule