TY - JOUR
T1 - The developmental impacts of natural selection on human pelvic morphology
AU - Young, Mariel
AU - Richard, Daniel
AU - Grabowski, Mark
AU - Auerbach, Benjamin M.
AU - de Bakker, Bernadette S.
AU - Hagoort, Jaco
AU - Muthuirulan, Pushpanathan
AU - Kharkar, Vismaya
AU - Kurki, Helen K.
AU - Betti, Lia
AU - Birkenstock, Lyena
AU - Lewton, Kristi L.
AU - Capellini, Terence D.
N1 - Funding Information: We would like to thank the University of Washington BDRL, supported by NIH award number 5R24HD000836 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development; C. Reardon and the Harvard Bauer Core Facility for ATAC-seq and RNA-seq assistance and sequencing; T. Sackton, J. Gaspar, and A. Freedman from the Bioinformatics group of Research Computing (Harvard University); S. Worthington (Harvard University) for statistics support and guidance; and C. Tabin (Harvard Medical School), D. Lieberman (Harvard University), M. Ruvolo (Harvard University), P. Reno (Philadelphia College of Osteopathic Medicine), S. Reilly (Broad Institute), A. Pollen (UCSF), D. Kingsley (Stanford University), and members of the Capellini laboratory (Harvard University) for critical insight and manuscript review. L.Be., M.G., B.M.A., H.K.K., and K.L.L. would also like to thank the curators and collection managers who granted access to skeletal remains in the many institutions at which osteometric data were collected. Funding: T.D.C., M.Y., P.M., and D.R. were supported by the Harvard University Dean’s Competitive Fund and Milton Fund for the functional genomics portion of this research. T.D.C. and M.Y. additionally received funds for mouse work from the National Science Foundation (BCS1518596 and BCS1847979). H.K.K. was supported by the Social Sciences and Humanities Research Council of Canada. Funding Information: The human products of conception at gestational days E53 to E59 were collected from first-trimester termination through the Birth Defects Research Laboratory (BDRL) at the University of Washington in full compliance with the ethical guidelines of the National Institutes of Health (NIH) and with the approval of the University of Washington Institutional Review Boards (IRB) for the collection and distribution of human tissues for research and Harvard University for the receipt and use of such materials. The BDRL obtained written consent from all tissue donors. The BDRL was supported by NIH award number 5R24HD000836 from the Eunice Kennedy Shriver Publisher Copyright: Copyright © 2022 The Authors, some rights reserved.
PY - 2022/8/19
Y1 - 2022/8/19
N2 - Evolutionary responses to selection for bipedalism and childbirth have shaped the human pelvis, a structure that differs substantially from that in apes. Morphology related to these factors is present by birth, yet the developmental-genetic mechanisms governing pelvic shape remain largely unknown. Here, we pinpoint and characterize a key gestational window when human-specific pelvic morphology becomes recognizable, as the ilium and the entire pelvis acquire traits essential for human walking and birth. We next use functional genomics to molecularly characterize chondrocytes from different pelvic subelements during this window to reveal their developmental-genetic architectures. We then find notable evidence of ancient selection and genetic constraint on regulatory sequences involved in ilium expansion and growth, findings complemented by our phenotypic analyses showing that variation in iliac traits is reduced in humans compared to African apes. Our datasets provide important resources for musculoskeletal biology and begin to elucidate developmental mechanisms that shape human-specific morphology.
AB - Evolutionary responses to selection for bipedalism and childbirth have shaped the human pelvis, a structure that differs substantially from that in apes. Morphology related to these factors is present by birth, yet the developmental-genetic mechanisms governing pelvic shape remain largely unknown. Here, we pinpoint and characterize a key gestational window when human-specific pelvic morphology becomes recognizable, as the ilium and the entire pelvis acquire traits essential for human walking and birth. We next use functional genomics to molecularly characterize chondrocytes from different pelvic subelements during this window to reveal their developmental-genetic architectures. We then find notable evidence of ancient selection and genetic constraint on regulatory sequences involved in ilium expansion and growth, findings complemented by our phenotypic analyses showing that variation in iliac traits is reduced in humans compared to African apes. Our datasets provide important resources for musculoskeletal biology and begin to elucidate developmental mechanisms that shape human-specific morphology.
UR - http://www.scopus.com/inward/record.url?scp=85136068955&partnerID=8YFLogxK
U2 - https://doi.org/10.1126/sciadv.abq4884
DO - https://doi.org/10.1126/sciadv.abq4884
M3 - Article
C2 - 35977020
SN - 2375-2548
VL - 8
SP - eabq4884
JO - Science advances
JF - Science advances
IS - 33
M1 - eabq4884
ER -