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Morgan, Bruce

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Morgan, Bruce
Author's Publications: search.filters.isAuthorOfPublication.f74b737f-08b9-4699-88a3-e6345e399a53

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    Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant
    (Elsevier BV, 2013) Kamberov, Yana; Wang, Sijia; Tan, Jingze; Gerbault, Pascale; Wark, Abigail; Tan, Longzhi; Yang, Yajun; Li, Shilin; Tang, Kun; Chen, Hua; Powell, Adam; Itan, Yuval; Fuller, Dorian; Lohmueller, Jason; Mao, Junhao; Schachar, Asa; Paymer, Madeline; Hostetter, Elizabeth; Byrne, Elizabeth; Burnett, Melissa; McMahon, Andrew P.; Thomas, Mark G.; Lieberman, Daniel; Jin, Li; Tabin, Clifford; Morgan, Bruce; Sabeti, Pardis
    An adaptive variant of the human Ectodysplasin receptor, EDARV370A, is one of the strongest candidates of recent positive selection from genome-wide scans. We have modeled EDAR370A in mice and characterized its phenotype and evolutionary origins in humans. Our computational analysis suggests the allele arose in central China approximately 30,000 years ago. Although EDAR370A has been associated with increased scalp hair thickness and changed tooth morphology in humans, its direct biological significance and potential adaptive role remain unclear. We generated a knockin mouse model and find that, as in humans, hair thickness is increased in EDAR370A mice. We identify new biological targets affected by the mutation, including mammary and eccrine glands. Building on these results, we find that EDAR370A is associated with an increased number of active eccrine glands in the Han Chinese. This interdisciplinary approach yields unique insight into the generation of adaptive variation among modern humans.
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    A genetic basis of variation in eccrine sweat gland and hair follicle density
    (Proceedings of the National Academy of Sciences, 2015) Kamberov, Yana; Karlsson, Elinor K; Kamberova, Gerda L.; Lieberman, Daniel; Sabeti, Pardis; Morgan, Bruce; Tabin, Clifford
    Among the unique features of humans, one of the most salient is the ability to effectively cool the body during extreme prolonged activity through the evapotranspiration of water on the skin's surface. The evolution of this novel physiological ability required a dramatic increase in the density and distribution of eccrine sweat glands relative to other mammals and a concomitant reduction of body hair cover. Elucidation of the genetic underpinnings for these adaptive changes is confounded by a lack of knowledge about how eccrine gland fate and density are specified during development. Moreover, although reciprocal changes in hair cover and eccrine gland density are required for efficient thermoregulation, it is unclear if these changes are linked by a common genetic regulation. To identify pathways controlling the relative patterning of eccrine glands and hair follicles, we exploited natural variation in the density of these organs between different strains of mice. Quantitative trait locus mapping identified a large region on mouse Chromosome 1 that controls both hair and eccrine gland densities. Differential and allelic expression analysis of the genes within this interval coupled with subsequent functional studies demonstrated that the level of En1 activity directs the relative numbers of eccrine glands and hair follicles. These findings implicate En1 as a newly identified and reciprocal determinant of hair follicle and eccrine gland density and identify a pathway that could have contributed to the evolution of the unique features of human skin.