Seminars

June 4 2014

12:00 LSB 2320

Michael Kohn
Institute of Biosciences and Bioengineering, Department of Ecology and Evolutionary Biology, Rice University

Evolution of anticoagulant rodenticide resistance in rodents

Summary

Evolution of adaptive traits progresses by selection and drift on mutations. The origin of mutations commonly recruited into adaptive traits remains to be determined; that is, whether these are new mutations or standing polymorphisms in populations, or whether these can even arise as a result from hybridization and introgression. Related to these questions there is a broad interest in understanding the relative roles of independent evolution within populations and species versus the role of gene flow in the origin and spread of adaptive traits. Lastly, the role, or function of polymorphisms encoding a complex adaptive trait needs to be better understood; with some encoding the trait while others modifying the trait or encoding compensatory functions. We study rodents resistant to anticoagulant rodenticides; of these warfarin is most commonly known. Resistance has evolved in parallel in several species of mice and rats. Moreover, it is found in geographically distinct populations within species of mice and rats, with numerous (and even an excess of) mutations found in the main resistance gene Vkorc1. We present results documenting the origin and spread of resistance alleles at Vkorc1, some of which have originated from hybridization and adaptive introgressiontion between species of mice. Moreover, we extend our study of this system to show that the genetics of resistance is complex and seemingly enriched for vitamin K related processes once studied using genomics approaches and gene interaction networks. Similarly, we study genome-wide patterns of introgression that led to resistance and propose an interesting scenario where driver mutations (introgressed alleles) provide an opportunity for selection on introgressed passenger alleles that encode novel traits as inferred by analyzing the mouse gene interaction networks. Our study of warfarin resistance offers a multitude of opportunities to study fundamental questions regarding the roles mutation, selection, gene flow, and hybridization play during the evolution of a complex adaptive trait, and to disentangle the timing, origin, and roles of adaptive polymorphisms. Our work has implications for the medical uses of warfarin, such as in personalized medicine, and the study of complex vitamin K related disease phenotypes in humans such as atheriosclerosis and osteoporosis.

 

 

 

 

 

 

 

 

 

 

 



 

 

 

 

 

 

 

 

 

 

 

 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



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