School of Medicine Publications and Presentations

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Experimental research on mice has yielded tremendous biological insight. However, the ∼140 million y of evolution that separate mice from humans pose a hurdle to direct application of this knowledge to humans. We report here that considerable progress for identifying genetically patterned skeletal phenotypes beyond the mouse model is possible through transdisciplinary approaches that include the anatomical sciences. Indeed, anatomy and paleontology offer unique opportunities through which to develop and test hypotheses about the underlying genetic mechanisms of the skeleton for taxa that are not well suited to experimental manipulation, such as ourselves.


Developmental genetics research on mice provides a relatively sound understanding of the genes necessary and sufficient to make mammalian teeth. However, mouse dentitions are highly derived compared with human dentitions, complicating the application of these insights to human biology. We used quantitative genetic analyses of data from living nonhuman primates and extensive osteological and paleontological collections to refine our assessment of dental phenotypes so that they better represent how the underlying genetic mechanisms actually influence anatomical variation. We identify ratios that better characterize the output of two dental genetic patterning mechanisms for primate dentitions. These two newly defined phenotypes are heritable with no measurable pleiotropic effects. When we consider how these two phenotypes vary across neontological and paleontological datasets, we find that the major Middle Miocene taxonomic shift in primate diversity is characterized by a shift in these two genetic outputs. Our results build on the mouse model by combining quantitative genetics and paleontology, and thereby elucidate how genetic mechanisms likely underlie major events in primate evolution.


Freely available online through the PNAS open access option.

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Office of Human Genetics



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