James M. Cheverud
My research focuses on evolutionary genetics, morphology, the genetics of complex traits and diseases in model organisms, and primate and mammalian evolution. Our studies of complex traits have been performed in non-human primates and in mice, as a model organism. We have studied a variety of traits, including cranial and skeletal morphology, obesity, diabetes, growth, brain morphology, congenital heart disease, scarless wound healing, arthritis, osteoporosis, and knee cartilage regeneration. In these studies we have documented that the effects of genes depend critically on their context, such as environment (high fat diet), sex, and alleles at other loci (epistasis). In general, genes do not have effects on their own but only in a complex web of specific genetic and environmental contexts. This work also aims to identify the genetic elements and nucleotide changes responsible for complex trait variation.
Since gene effects vary depending on context, these effects are genetically variable and will evolve. In a number of studies in mice and opossums, we have shown that the effects of genes on single traits and on a range of multiple traits (pleiotropy) are genetically variable. We have shown that directional natural selection will result in the evolution of gene effects to increase variation along the selected dimension, thereby accelerating adaptation.
We have also been involved in many studies of systematics and evolution in non-human primates and in human evolution. In these studies we have shown that complex phenotypes tend to be modular with functionally and developmentally traits sharing their underlying genetic bases (morphological evolution) and that patterns of heritable variation can prove critical in either constraining or facilitating adaptation. We have used modern evolutionary quantitative genetic models to examine the historical forces, genetic drift and natural selection, responsible for the observed morphological diversification of primates, with special emphasis on the New World Monkeys.
Porto, A, H. Sebastião, S. E. Pavan, J. L. VandeBerg, G. Marroig and J. M.Cheverud. 2015. Rate of evolutionary change in cranial morphology of the marsupial genus Monodelphis is constrained by the availability of additive genetic variation. Journal of Evolutionary Biology 28:973-985.
Pavličev, M. and J. M. Cheverud. 2015. Constraints evolve: context-dependency of gene effects allows evolution of pleiotropy. Annual Review of Evolution, Ecology, and Systematics 46: (in press).
Atkinson, E. G., J. Rogers, M. C. Mahaney, L. A. Cox, and J. M. Cheverud. 2015. Cortical folding of the primate brain: An interdisciplinary examination of the genetic architecture, modularity, and evolvability of a significant neurological trait in pedigreed baboons (genus Papio). Genetics 200: 651-665.
Nikolskiy, I., D. F. Conrad, S. Chun, J. C. Fay, J. M. Cheverud, and H. A. Lawson. 2015. Using whole-genome sequences of the LG/J and SM/J inbred mouse strains to prioritize quantitative trait genes and nucleotides. BMC Genomics 16:415 (12 pg.).
Schroeder, L., C.C. Roseman, J. M. Cheverud, R. R. Ackermann. 2014. Characterizing the evolutionary path(s) to early Homo. PLoS ONE 9(12): e114307. doi:10.1371/journal.pone.0114307
Cheverud, J. M., H. A. Lawson, K. Bouckaert, A. V. Kossenkov, L. C. Showe, L. Cort, E. P. Blankenhorn, K. Bedelbaeva, D. Gourevitch, Y. Zhang, and E. Heber-Katz. 2014. Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line. Heredity 112: 508-518. doi: 10.1038/hdy.2013.133
Partridge, C, G. L. Fawcett, B. Wang, C. F. Semenkovich, and J. M. Cheverud. 2014. The effect of dietary fat intake on hepatic gene expression in LG/J AND SM/J mice. BMC Genomics 15:99.
Lawson, H. A., J. M. Cheverud, and J. B. Wolf. 2013. Genomic imprinting and parent-of-origin effects on complex traits. Nature Reviews Genetics, 14: 609-617.
Minkina, O., Cheverud, J. M., Fawcett, G. L., Semenkovich, C. F. and J. P. Kenney-Hunt. 2012. Quantitative trait loci affecting liver fat content in mice. G3: Genes, Genomes, Genetics 2: 1019-1025.
Carson, E. A., Kenney-Hunt, J. P., Pavlicev, M.; Bouckaert, K. A., Chinn, A. J., Silva, M. J., Cheverud, J. M. 2012. Weak genetic relationship between trabecular bone morphology and obesity in mice. Bone 51: 46-53.
Wolf, J. B. and J. M. Cheverud. 2012. Detecting maternal effect loci by statistical cross fostering. Genetics 191: 261-277.
Lawson, H. A., A. Lee, G. L. Fawcett, B. Wang, L. S. Pletscher, T. J. Maxwell, T. H. Ehrich, J. P. Kenney-Hunt, J. B. Wolf, C. F. Semenkovich and J. M. Cheverud. 2011. The importance of context to the genetic architecture of diabetes-related traits is revealed in a genome-wide scan of a LG/J x SM/J murine model. Mammalian Genome 22: 197-208.
Sanger, T. J., E. A. Norgard, L. S. Pletscher, M. Bevilacqua, V. R. Brooks, L. M. Sandell, and J. M. Cheverud. 2011. Developmental and genetic origins of murine long bone length variation. Journal of Experimental Zoology (Molecular and Developmental Evolution), 316: 146-161.
Cheverud, J. M., H. A. Lawson, G. L. Fawcett, B. Wang, L. S. Pletscher, A. Fox, T. J. Maxwell, T. H. Ehrich, J. P. Kenney-Hunt, J. B. Wolf and C. F. Semenkovich. 2011. Diet-dependent genetic and genomic imprinting effects on obesity in mice. Obesity 19: 160-170; doi:10.1038/oby.2010.141.
Lawson, H. A., K. M. Zelle, G. L. Fawcett, B. Wang, L. S. Pletscher, T. J. Maxwell, T. H. Ehrich, J. P. Kenney‐Hunt, J. B. Wolf, C. F. Semenkovich, and J. M. Cheverud. 2010. Genetic, epigenetic, and gene‐by‐diet interaction effects underlie variation in serum lipids in a LG/J x SM/J murine model. Journal of Lipid Research 51: 2976-2984 ; doi:10.1194/jlr.M006957.