Assistant Professor of Biology
Ph.D. University of Rochester, Biology (2011)
Areas of Expertise
Genetics and Evolution
- Winter Study Committee
I am interested in identifying general principles of how adaptive evolution shapes gene function in multicellular organisms. Knowledge of these principles is essential to our ability to predict the phenotypic consequences of mutations and variation from whole genome sequences.
One universal aspect of gene function evolution that has been largely unexplored is quantitative: how much protein or enzyme activity is produced by a gene. This is of particular interest in animal genomes, due to their complex gene regulation and the link to human biology. Open questions about quantitative gene evolution include: Do all aspects of gene structure contribute to adaptive functional change? When parallel quantitative adaptations occur in different lineages, do these follow similar paths, changing the same gene structures or nucleotides? What are the relative contributions of protein coding changes, cis-regulatory substitutions, and gene duplications? Do the same rules apply at different scales – is variation within populations representative of differences between species?
Genetic mechanisms of adaptive evolution
To study how genes change during adaptive evolution, my lab focuses on the model trait of alcohol metabolism in Drosophila flies. Most Drosophila species feed on fermenting fruits, but some species have adapted to low-alcohol foods like mushrooms whereas others actually prefer the alcohol-rich environments of breweries and wine cellars. We study how the Alcohol dehydrogenase (Adh) gene changed in these species. The lab uses techniques of molecular cloning, transgenics, and high-throughput enzyme and gene expression assays to precisely measure the quantitative differences in enzyme activity that have accompanied these shifts in diet. This is a fertile research area, with multiple paths to investigate.
One early insight is that the primary way that ADH enzyme activity changes is through regulatory sequence changes (i.e., by altering protein levels), whereas changes to the structure of the protein itself are a relatively minor contributor. It will be exciting to find out if the same parts of the gene have changed in the several species that has adapted to high or low alcohol environments, or if these separate evolutionary events followed different mutational paths.
Phenotypic consequences of gene duplication
One surprise from the study of Adh is that tandemly duplicated genes in Drosophila often do not produce 2-fold higher output than single copy genes (Loehlin and Carroll 2016, or watch conference presentation [slideshow+voice]). Basically, tandem duplicates of the whole Adh gene, or of unrelated reporter constructs, show enzyme activity and transcript levels that are greater than twice that of the single copy.
This “overactivity” has not been observed before, and appears to go in the opposite direction of evolutionary trends of tandem duplicate expression. I am particularly curious to find out how widespread this overactivity phenomenon occurs, if it persists over evolutionary time, and what mechanisms underpin it.
Please view my Google Scholar page for recent publications and links.
Loehlin DL, JR Ames (Williams class of 2019), K Vaccaro, SB Carroll. (2019) A major role for noncoding regulatory mutations in the evolution of enzyme activity. Proceedings of the National Academy of Sciences https://doi.org/10.1073/pnas.1904071116
Siddiq MA, Loehlin DW, Montooth KL, Thornton JW. (2017) Test and refutation of a classic hypothesis of molecular adaptation. Nature Ecology and Evolution 1(0025). doi: 10.1038/s41559-016-0025
Loehlin D.W. and S.B. Carroll. (2016) Expression of tandem gene duplicates is often greater than twofold. PNAS 113(21):5988–5992. doi: 10.1073/pnas.1605886113
Loehlin D.W. and S.B. Carroll. (2014) News and Views: Sex, Lies and Butterflies. Nature 507(7491): 172-173.
Chung, H., D.W. Loehlin, H.D. Dufour, K. Vaccaro, J.G. Millar, and S.B. Carroll. (2014) A single gene affects both ecological divergence and mate choice in Drosophila. Science 343(6175): 1148-1151.
Desjardins, C.A., …, D. W. Loehlin, et al. (2013). Fine-scale mapping of the Nasonia genome to chromosomes using a high-density genotyping microarray. G3 3(2): 205-215.
Loehlin, D.W. and J.H. Werren. (2012). Evolution of Shape by Multiple Regulatory Changes to a Growth Gene. Science 335: 943-947.
Loehlin, D.W., D.C.S.G Oliveira, R. Edwards, J.D. Giebel, M. Clark, M.V. Cattani, L. van de Zande, E. Verhulst, L.W. Beukeboom, M. Munoz-Torres, and J.H. Werren (2010). Non-coding Changes Cause Sex-specific Wing Size Differences Between Closely Related Species of Nasonia. PLoS Genetics 6(1): e1000821.
Loehlin D.W., L.S. Enders and J.H. Werren. (2010) Evolution of sex-specific wing shape at the widerwing locus in four species of Nasonia. Heredity 104(3): 260-269.
Werren, J.H., … D.W. Loehlin, et al. (2010) Functional and evolutionary insights from the genomes of three parasitoid Nasonia species. Science 327(5963): 343-348.
Raychoudhury R., C.A. Desjardins, J. Buellesbach, D.W. Loehlin, B.K. Grillenberger, L. Beukeboom, T. Schmitt and J.H. Werren. 2010. Behavioural and Genetic Characteristics of a New Species of Nasonia. Heredity 104(3): 278-288.
Werren, J.H. and D.W. Loehlin (2009). The Parasitoid Wasp Nasonia: An Emerging Model System with Haploid Male Genetics. Cold Spring Harbor Protocols doi:10.1101/pdb.emo134