The primary focus of my research is the genetic basis of adaptive evolutionary change. Research in my lab integrates molecular population genetics, molecular evolution, comparative genomics, structural biology, and experimental studies of protein function.

GENETICS OF ADAPTATION TO HIGH ALTITUDE

In my lab we are studying functional genetic variation in natural populations of deer mice (genus Peromyscus), leaf-eared mice (genus Phyllotis), house mice (genus Mus), and other small mammals to elucidate genetic mechanisms of physiological adaptation to different environments. We are especially interested in mechanisms of physiological adaptation to high-altitude hypoxia. To this end we are currently studying the molecular evolution of protein-coding genes involved in oxygen transport, oxygen storage, and aerobic energy metabolism. For example, one of our main projects involves a study of hemoglobin polymorphism that underlies adaptive variation in blood biochemistry and aerobic metabolism among deer mice that are native to different altitudes. We are currently conducting surveys of DNA sequence variation in the duplicated globin genes of deer mice from different mountain ranges across western North America. The goals of this project are to determine how patterns of adaptive genetic variation are shaped by the interplay between selection, recombination, and gene conversion, and to assess the relative importance of different modes of selection in maintaining balanced polymorphism at interacting genes.

EVOLUTION OF DUPLICATED GENES AND MULTIGENE FAMILIES

A second area of research is geared towards understanding mechanism and process in genome evolution. We are especially interested in the role of gene duplication in the expansion and functional diversification of multigene families. Gene duplication is thought to play an extremely important role in the evolution of novel protein functions. However, there is still much debate about the specific evolutionary mechanisms that are responsible for the initial retention and subsequent functional divergence of duplicated genes. The globin superfamily of genes is an ideal model system for addressing questions about genome evolution because it is one of the most intensively studied multigene families from the standpoint of molecular genetics and phylogenetic history. The globin gene families also provide an excellent example of the kind of physiological versatility that can be attained through functional and regulatory divergence of duplicated genes that encode different subunit polypeptides of the same multimeric protein. For example, in gnathostome vertebrates, different hemoglobin isoforms have been optimized for oxygen transport under the vastly different physiological conditions encountered during the embryonic, fetal, and adult stages of development. We are currently integrating comparative genomic analyses of the globin gene families of different vertebrate taxa with experimental studies of hemoglobin function. The ultimate goal is to link changes in the size and membership composition of the globin gene families to key physiological innovations in the oxygen transport systems of different species.

Current grants

NIH - "Mechanisms of Hemoglobin Adaptation to Hypoxia in High Altitude Rodents" (2008-2013)

NIH - National Heart, Lung, and Blood Institute, ARRA Supplement Award (2009-2011)

NSF - "A Test of Adaptive Divergence across Altitudinal Gradients: Population Genomics of Deer Mice" (2006-2009)