I use population genetic theory and high-throughput biological sequence analysis to study recent evolutionary history in humans and other species. One of my primary research interests is the evolution of mutagenesis–I want to understand the forces that control DNA replication fidelity, the mutational breakdown of established traits, and the ultimate origin of new traits. Although DNA is replicated and repaired by highly conserved housekeeping pathways, the mutation rate appears to evolve surprisingly rapidly over evolutionary time. One way to see this is to compare the relative mutation rates of different 3-base-pair DNA motifs, expanding a one-dimensional "mutation rate" into a rich, multidimensional "mutation spectrum." Due to changes in the mutation rates of particular DNA motifs, each human population and great ape species appears to have its own distinctive mutational spectrum that results from a unique set of mutational challenges and repair processes. My lab will work to decipher how this variation is genetically and environmentally determined and what evolutionary pressures (such as cancer, congenital disease, or life history) might be driving mutagenesis to change.
I am also broadly interested in the impact of demography, inbreeding, and hybridization on the dynamics of natural selection, particularly in the wake of gene flow between humans, Neanderthals, and other extinct hominids. I have developed a variety of computational methods for inferring population bottlenecks, divergence times, and admixture events at high resolution, and have written about the impact of Neanderthal interbreeding on the fitness of archaic and modern humans. My group will continue developing new statistical models that refine our understanding of how genomes and populations evolve, using methods derived from coalescent theory to visualize and extract the information contained in huge databases of whole genomes.
K. Harris and Jonathan K. Pritchard. "Rapid evolution of the human mutation spectrum." eLife 6 (2017).
K. Harris and Rasmus Nielsen. "The genetic cost of Neanderthal introgression." Genetics 203 (2016).
M. Raghavan,* M. Steinruecken,* K. Harris,* S. Schiffels,* S. Rasmussen,* M. DeGiorgio,* A. Albrechtsen,* C. Valdiosera,* M.C. Avila-Arcos,* A.-S. Malaspinas,* A. Eriksson, et al. "Genomic evidence for the Pleistocene and recent population history of Native Americans." Science 349 (2015).
K. Harris. "Evidence for recent, population-specific evolution of the human mutation rate." Proc Natl Acad Sci USA 112 (2015).
K. Harris and R. Nielsen. "Error-prone polymerase activity causes multinucleotide mutations in humans." Genome Research 24 (2014).
K. Harris, S. Sheehan, J.A. Kamm, and Y.S. Song. "Decoding coalescent hidden Markov models in linear time." Research in Computational Molecular Biology (2014).
S. Sheehan,* K. Harris,* and Y.S. Song. "Estimating variable effective population sizes from multiple genomes: a sequentially Markov conditional sampling distribution approach." Genetics 194 (2013).
K. Harris and R. Nielsen. "Inferring demographic history from a spectrum of shared haplotype lengths." PLoS Genetics (2013).