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Myosin gene mutation correlates with anatomical changes in the human lineage

Abstract

Powerful masticatory muscles are found in most primates, including chimpanzees and gorillas, and were part of a prominent adaptation of Australopithecus and Paranthropus, extinct genera of the family Hominidae1,2. In contrast, masticatory muscles are considerably smaller in both modern and fossil members of Homo. The evolving hominid masticatory apparatus—traceable to a Late Miocene, chimpanzee-like morphology3—shifted towards a pattern of gracilization nearly simultaneously with accelerated encephalization in early Homo4. Here, we show that the gene encoding the predominant myosin heavy chain (MYH) expressed in these muscles was inactivated by a frameshifting mutation after the lineages leading to humans and chimpanzees diverged. Loss of this protein isoform is associated with marked size reductions in individual muscle fibres and entire masticatory muscles. Using the coding sequence for the myosin rod domains as a molecular clock, we estimate that this mutation appeared approximately 2.4 million years ago, predating the appearance of modern human body size5 and emigration of Homo from Africa6. This represents the first proteomic distinction between humans and chimpanzees that can be correlated with a traceable anatomic imprint in the fossil record.

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Figure 1: Molecular evolution of MYH16.
Figure 2: Transcription of MYH16.
Figure 3: Selective loss of type II myofibre size and muscle bulk in the human temporalis.
Figure 4: Divergence of the MYH16 orthologue.

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Acknowledgements

We thank K. Brayman, N. Mirza, M. Ruckenstein and the University of Washington National Primate Research Center (Seattle) for providing access to the biopsy material used in this study; N. Gilmore of the Philadelphia Academy of Natural Sciences for access to specimens for photography; L. Joseph, D. Fonseca, R. McCourt and W. Ewens for assistance with the bioinformatic analysis; and P. Dodson, L. Whitaker, A. Kelly and S. Bartlett for advance reading of the manuscript. We also thank colleagues in the University of Pennsylvania Genomics Institute Bioinformatics Core, and Wistar Institute Proteomics Facility for their assistance. This work was supported in part by grants to H.H.S. from the NIH (NIAMS and NINDS), MDA, AFM, VA and the Genzyme Corporation.

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Correspondence to Hansell H. Stedman.

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Stedman, H., Kozyak, B., Nelson, A. et al. Myosin gene mutation correlates with anatomical changes in the human lineage. Nature 428, 415–418 (2004). https://doi.org/10.1038/nature02358

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