Ryan N Gutenkunst

Ryan N Gutenkunst

Associate Department Head, Molecular and Cellular Biology
Associate Professor, Applied BioSciences - GIDP
Associate Professor, Applied Mathematics - GIDP
Associate Professor, Cancer Biology -
Associate Professor, Ecology and Evolutionary Biology
Associate Professor, Genetics - GIDP
Associate Professor, Molecular and Cellular Biology
Associate Professor, Public Health
Associate Professor, Statistics-GIDP
Associate Professor, BIO5 Institute
Member of the Graduate Faculty
Director, Graduate Studies
Primary Department
(520) 626-0569

Work Summary

We learn history from the genomes of humans, tumors, and other species. Our studies reveal how evolution works at the molecular level, offering fundamental insight into how humans and pathogens adapt to challenges.

Research Interest

The Gutenkunst group studies the function and evolution of the complex molecular networks that comprise life. To do so, they integrate computational population genomics, bioinformatics, and molecular evolution. They focus on developing new computational methods to extract biological insight from genomic data and applying those methods to understand population history and natural selection.


Qi, X., An, H., Ragsdale, A. P., Hall, T. E., Gutenkunst, R. N., Pires, J. C., & Barker, M. S. (2017). Genome wide analyses of diverse Brassica rapa cultivars reveal significant genetic structure and corroborate historical record of domestication. Molecular Ecology.
BIO5 Collaborators
Michael S Barker, Ryan N Gutenkunst
Dornhaus, A. R., Gutenkunst, R. N., Wang, X., & Leighton, G. M. (2017). Behavioral caste is associated with distinct gene expression profiles in workers in Temnothorax rugatulus. BMC Genomics.
BIO5 Collaborators
Anna R Dornhaus, Ryan N Gutenkunst
Veeramah, K. R., Gutenkunst, R. N., Woerner, A. E., Watkins, J. C., & Hammer, M. F. (2014). Evidence for increased levels of positive and negative selection on the X chromosome versus autosomes in humans. Molecular biology and evolution, 31(9), 2267-82.

Partially recessive variants under positive selection are expected to go to fixation more quickly on the X chromosome as a result of hemizygosity, an effect known as faster-X. Conversely, purifying selection is expected to reduce substitution rates more effectively on the X chromosome. Previous work in humans contrasted divergence on the autosomes and X chromosome, with results tending to support the faster-X effect. However, no study has yet incorporated both divergence and polymorphism to quantify the effects of both purifying and positive selection, which are opposing forces with respect to divergence. In this study, we develop a framework that integrates previously developed theory addressing differential rates of X and autosomal evolution with methods that jointly estimate the level of purifying and positive selection via modeling of the distribution of fitness effects (DFE). We then utilize this framework to estimate the proportion of nonsynonymous substitutions fixed by positive selection (α) using exome sequence data from a West African population. We find that varying the female to male breeding ratio (β) has minimal impact on the DFE for the X chromosome, especially when compared with the effect of varying the dominance coefficient of deleterious alleles (h). Estimates of α range from 46% to 51% and from 4% to 24% for the X chromosome and autosomes, respectively. While dependent on h, the magnitude of the difference between α values estimated for these two systems is highly statistically significant over a range of biologically realistic parameter values, suggesting faster-X has been operating in humans.

Andrés, A. M., Hubisz, M. J., Indap, A., Torgerson, D. G., Degenhardt, J. D., Boyko, A. R., Gutenkunst, R. N., White, T. J., Green, E. D., Bustamante, C. D., Clark, A. G., & Nielsen, R. (2009). Targets of balancing selection in the human genome. Molecular Biology and Evolution, 26(12), 2755-2764.

PMID: 19713326;PMCID: PMC2782326;Abstract:

Balancing selection is potentially an important biological force for maintaining advantageous genetic diversity in populations, including variation that is responsible for long-term adaptation to the environment. By serving as a means to maintain genetic variation, it may be particularly relevant to maintaining phenotypic variation in natural populations. Nevertheless, its prevalence and specific targets in the human genome remain largely unknown. We have analyzed the patterns of diversity and divergence of 13,400 genes in two human populations using an unbiased single-nucleotide polymorphism data set, a genome-wide approach, and a method that incorporates demography in neutrality tests. We identified an unbiased catalog of genes with signatures of long-term balancing selection, which includes immunity genes as well as genes encoding keratins and membrane channels; the catalog also shows enrichment in functional categories involved in cellular structure. Patterns are mostly concordant in the two populations, with a small fraction of genes showing population-specific signatures of selection. Power considerations indicate that our findings represent a subset of all targets in the genome, suggesting that although balancing selection may not have an obvious impact on a large proportion of human genes, it is a key force affecting the evolution of a number of genes in humans.

Lynch, M., Gutenkunst, R., Ackerman, M., Spitze, K., Ye, Z., Maruki, T., & Jia, Z. (2017). Population Genomics of Daphnia pulex. Genetics, 206, 315.

Using data from 83 isolates from a single population, the population genomics of the microcrustacean Daphnia pulex are described and compared to current knowledge for the only other well-studied invertebrate, Drosophila melanogaster These two species are quite similar with respect to effective population sizes and mutation rates, although some features of recombination appear to be different, with linkage disequilibrium being elevated at short ( 100 bp) distances in D. melanogaster and at long distances in D. pulex The study population adheres closely to the expectations under Hardy-Weinberg equilibrium, and reflects a past population history of no more than a two-fold range of variation in effective population size. Four-fold redundant silent sites and a restricted region of intronic sites appear to evolve in a nearly neutral fashion, providing a powerful tool for population-genetic analyses. Amino-acid replacement sites are predominantly under strong purifying selection, as are a large fraction of sites in UTRs and intergenic regions, but the majority of SNPs at such sites that rise to frequencies > 0:05 appear to evolve in a nearly neutral fashion. All forms of genomic sites (including replacement sites within codons, and intergenic and UTR regions) appear to be experiencing an ~ 2x higher level of selection scaled to the power of drift in D. melanogaster, but this may in part be a consequence of recent demographic changes. These results establish D. pulex as an excellent system for future work on the evolutionary genomics of natural populations.