A genomic approach to identify hybrid incompatibility genes

Abstract

Uncovering the genetic and molecular basis of barriers to gene flow between populations is key to understanding how new species are born. Intrinsic postzygotic reproductive barriers such as hybrid sterility and hybrid inviability are caused by deleterious genetic interactions known as hybrid incompatibilities. The difficulty in identifying these hybrid incompatibility genes remains a rate-limiting step in our understanding of the molecular basis of speciation. We recently described how whole genome sequencing can be applied to identify hybrid incompatibility genes, even from genetically terminal hybrids. Using this approach, we discovered a new hybrid incompatibility gene, gfzf, between Drosophila melanogaster and Drosophila simulans, and found that it plays an essential role in cell cycle regulation. Here, we discuss the history of the hunt for incompatibility genes between these species, discuss the molecular roles of gfzf in cell cycle regulation, and explore how intragenomic conflict drives the evolution of fundamental cellular mechanisms that lead to the developmental arrest of hybrids.

Keywords: Drosophila; cell cycle; genomic conflict; hybrid incompatibility; speciation.

Figure 1.

gfzf activity causes an arrest in cell cycle progression. The pn-Kpn-gfzf system and Hmr-Lhr-gfzf hybrid incompatibility both cause an arrest in cell cycle progression similar to gfzf homozygous null mutations. This leads to a developmental arrest and eventual death of larvae. Together, these forms of lethality highlight the surprising role of cell cycle regulation in dominant incompatibilities.

Figure 2.

Intragenomic arms races between the selfish genetic elements and the cellular machinery drive the evolution of hybrid incompatibilities. Interactions between selfish elements and host genomes co-evolve as selection favors selfish elements that can evade host defenses. This in turn triggers an evolutionary response favoring host variants that can defend themselves from selfish elements. The genes that are at the interface of these conflicts are predicted to diverge rapidly under selection, and can lead them to become incompatible between species.