Research Focus

The biology and evolution of genomes

Our work is guided by the principle that answers to complex and important problems should not be confined by rigid disciplinary boundaries. Thus, we are primarily motivated by important biological questions and use both experimental, computational, and theoretical methods in our research. Our favorite "model organisms" are yeast, dogs, and humans, each of which are uniquely poised to answer specific questions about the biology and evolution of genomes. More specific information about current research in each of these organisms is provided below.

Humans. We have a long-standing interest in human population genomics, with a particular emphasis on identifying regions of the genome that have been substrates of recent adaptive evolution. Although not typically viewed as a model organism, humans have become a powerful system to study genome-wide patterns of natural selection, as considerable sequence and polymorphism data exists in geographically diverse populations. We maintain an interest in developing and applying novel statistical and computational approaches for detecting selection, and have more recently been using new large-scale datasets to address questions about selection, demographic history, and archaic introgression.

Yeast. We are currently using yeast as a model system to understand the genetic architecture and evolution of high-dimensional molecular phenotypes such as gene expression, protein expression, and metabolite levels. The rapidly accumulating complete genome sequences of natural yeast isolates combined with these functional genomics phenotypes provides a powerful, and challenging, opportunity to more comprehensively understand how genetic and environmental variation conspire to produce phenotypic variation.

Dogs. Our research in canine genomics is currently focused on two projects. First, we are studying the genetic basis of adverse drug responses observed across breeds. This work is being performed in collaboration with Katrina Mealey at Washington State University. Second, we have characterized the genomic distribution of segmental duplications and copy number variants (CNVs) within and between different breeds. Our CNV projects are done in close collaboration with Evan Eichler, also in the Department of Genome Sciences.

Selected Publications

• Bray EE, Zheng Z, Tolbert MK, McCoy BM; Dog Aging Project Consortium, Kaeberlein M, Kerr KF. 2022. Once-daily feeding is associated with better health in companion dogs: results from the Dog Aging Project. Geroscience. 2022 Apr 28. doi: 10.1007/s11357-022-00575-7. Online ahead of print. Pubmed

• Creevy KE, Akey JM, Kaeberlein M, Promislow DEL; Dog Aging Project Consortium. 2022. An open science study of ageing in companion dogs. Nature. 602(7895):51-57. Pubmed

• Xu H, Zhen Q, Bai M, Fang L, Zhang Y, Li B, Ge H, Moon S, Chen W, Fu W, Xu Q, Zhou Y, Yu Y, Lin L, Yong L, Zhang T, Chen S, Liu S, Zhang H, Chen R, Cao L, Zhang Y, Zhang R, Yang H, Hu X, Akey JM, Jin X, Sun L. 2021. Deep sequencing of 1320 genes reveals the landscape of protein-truncating variants and their contribution to psoriasis in 19,973 Chinese individuals. Genome Res. 31(7):1150-8. Pubmed

• Saad-Roy CM, Arinaminpathy N, Wingreen NS, Levin SA, Akey JM, Grenfell BT. 2020. Implications of localized charge for human influenza A H1N1 hemagglutinin evolution: Insights from deep mutational scans. PLoS Comput Biol. 16(6):e1007892. Pubmed

• Chen L, Wolf AB, Fu W, Li L, Akey JM. 2020. Identifying and Interpreting Apparent Neanderthal Ancestry in African Individuals. Cell. 80(4):677-687.e16. Pubmed

View complete list of Publications.