Joshua Akey Position Professor, Lewis-Sigler Institute for Integrative Genomics Title Lewis-Sigler Institute for Integrative Genomics Office Phone 609-258-9383 Email [email protected] Assistant Laura Hoffman Office 143 Carl Icahn Laboratory Bio/Description Research FocusThe biology and evolution of genomesOur 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.Google Scholar Selected Publications Bray, Emily, Zihan Zheng, Katherine Tolbert, Brianah McCoy, Dog Consortium, Matt Kaeberlein, and Kathleen Kerr. (2022) 2022. “Once-Daily Feeding Is Associated With Better Health in Companion Dogs: Results from the Dog Aging Project.”. GeroScience 44 (3): 1779-90. doi:10.1007/s11357-022-00575-7. Creevy, Kate, Joshua Akey, Matt Kaeberlein, Daniel Promislow, and Dog Consortium. (2022) 2022. “An Open Science Study of Ageing in Companion Dogs.”. Nature 602 (7895): 51-57. doi:10.1038/s41586-021-04282-9. Xu, Huixin, Qi Zhen, Mingzhou Bai, Lin Fang, Yong Zhang, Bao Li, Huiyao Ge, et al. (2021) 2021. “Deep Sequencing of 1320 Genes Reveals the Landscape of Protein-Truncating Variants and Their Contribution to Psoriasis in 19,973 Chinese Individuals.”. Genome Research 31 (7): 1150-8. doi:10.1101/gr.267963.120. Saad-Roy, Chadi, Nimalan Arinaminpathy, Ned Wingreen, Simon Levin, Joshua Akey, and Bryan Grenfell. (2020) 2020. “Implications of Localized Charge for Human Influenza A H1N1 Hemagglutinin Evolution: Insights from Deep Mutational Scans.”. PLoS Computational Biology 16 (6): e1007892. doi:10.1371/journal.pcbi.1007892. Chen, Lu, Aaron Wolf, Wenqing Fu, Liming Li, and Joshua Akey. (2020) 2020. “Identifying and Interpreting Apparent Neanderthal Ancestry in African Individuals.”. Cell 180 (4): 677-687.e16. doi:10.1016/j.cell.2020.01.012. Related News ‘A history of contact’: Princeton geneticists are rewriting the narrative of Neanderthals and other ancient humansWhat is your dog's lifespan? Joshua Akey seeking the keys to canine health and longevityNew study, led by Joshua Akey, identifies Neanderthal ancestry in African populations and describes its originModern Flores Island pygmies show no genetic link to extinct ‘hobbits’ Program(s) NIH NHGRI Training Program QCB Graduate Program Research Area Computational Genomics Evolutionary and Population Genomics Statistical Genomics LSI Research Lab Akey Research Lab