Population Genomics, Hybrid Sterility, & Gene Expression in the Anopheles gambiae Species Complex

Abstract

This dissertation explores the genomics of speciation in the An. gambiae complex. The complex is comprised of eight recently diverged species and contains the most important vectors of human malaria. Male F1 hybrids between these species are completely sterile and females exhibit varying levels of sterility. I performed a population genomic analysis of the three genetic clusters that comprise An. melas that illuminated genome-wide divergence between them. This is suggestive of a pattern of allopatric divergence with little to no gene flow.

I analyzed gene expression data to assess if dosage compensation occurs in males of An. coluzzii, An. arabiensis, and An. quadriannulatus, in order to balance expression between the hemizygous X chromosome and the autosomes. Dosage compensation is acting in each species and is not influenced by hybridization. I identified male- and female-biased genes in each parental species and mis-expressed genes in F1 hybrid males that are involved in hybrid sterility. Mis-expressed genes are involved in mitosis, spermatogenesis, and other physiological processes involved in the sterility phenotype. An analysis of allele-specific expression found that An. coluzzii and An. arabiensis have a high proportion of genes (~80%) that are conserved or compensatory in their transcription. In contrast, An. coluzzii and An. quadriannulatus have a higher proportion of genes that have diverged in trans-. These patterns may reflect higher levels of historical and ongoing introgression between An. coluzzii and An. arabiensis than between An. coluzzi and An. quadriannulatus.

Lastly, I performed a QTL analysis of sterility in a (An. coluzzi x An. quadriannulatus) x An. quadriannulatus backcross to identify regions of the An. coluzzi genome that are responsible for male sterility when introgressed into an An. quadriannulatus genomic background. Five autosomal QTL were identified that interact through epistatic interactions with each other and the X chromosome, which is responsible for the majority of the variation observed in the sterility phenotype. Two autosomal QTL of large effect are shared with the An. coluzzi x An. arabiensis cross, indicating that these regions of the An. coluzzii genome contribute to reproductive isolation between this species and multiple members of the An. gambiae species complex.