Evolutionary genomic analyses of adaptive evolution:
Our main research is concerned with the detection of adaptations at the level of genes or groups of genes. Our work involves molecular and computational analyses of genes, sets of genes, and whole genomes. Moreover we adopt a genetic network perspective, in that we attempt to not only identify the genes that appear to be the direct target of selection, but we are also interested in the population genetic and molecular evolutionary dynamics of genes that interact with these. Finally, our goal is to use comparatively well-established cases of genes under selection to work on analytical improvements to more routinely detect groups of interacting genes that mediate an adaptation.
While we are broadly interested in a number of adaptations, we currently focus on populations of rats and mice that have evolved resistance to anticoagulant rodent poisons, including warfarin and bromadiolone. The reason for our focus on this adaptation is that rodent poisons exert rather strong selection pressures on populations. Thus, if the population genetic signature of selection indeed can be detected for groups of interacting genes, then we would expect this to be more readily detected in a system where selection pressures are intense. Moreover, we have reasonably good prior knowledge about the molecular targets of selection with warfarin, and the main target gene has been identified as a vitamin K epoxide reductase.
The strong selection pressure by warfarin can easily be seen in warfarin resistant rat populations, where a large genomic area surrounding the warfarin resistance gene (vitamin K epoxide reductase) is affected by a selective sweep. We hypothesize that genes that interact with the vitamin K epoxide reductase might be affected by selective sweeps also. Groups of interacting genes are analyzed to discern the nature and type of genetic interactions, and how these lead to correlations of population genetic measures at interacting genes.
Besides focusing on warfarin resistance, we also study adaptation at the level of genes in broader terms. For example, we found evidence for selection on the non-coding DNA of genes that play important role in male reproductive processes of Drosophila males.
Representative publications:
- Michael H. Kohn, Hans-Joachim Pelz, & Robert K. Wayne (2000) Natural selection mapping of the warfarin resistance gene. The Proceedings of the National Academy of Sciences, USA 97: 7911-7915.
- Michael H. Kohn, Shu Fang & Chung-I Wu (2004) Inference of positive and negative selection on the 5' regulatory regions of Drosophila genes. Molecular Biology & Evolution 21: 374-383.
Rat race to speciation - the genus Rattus is among the most specious of all mammals and the rate at which new species have evolved is among the fastest currently reported (MHK unpublished).