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 Hominidae. 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 morphology--shifted towards a pattern of gracilization nearly simultaneously with accelerated encephalization in early Homo. 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 size and emigration of Homo from Africa. 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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Inactivation (loss) of ancestral protein-coding genes is one genetic mechanism contributing to phenotypic differences.
“One genetic mechanism contributing to phenotypic differences is the inactivation (loss) of ancestral protein-coding genes10,11.”
From A genomics approach reveals insights into the importance of gene losses for mammalian adaptations (2018) · cites this paper as [10]
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- Authors
- Stedman, H. H., Kozyak, B. W., Nelson, A., Thesier, D. M., Su, L. T., Low, D. W., Bridges, C. R., Shrager, J. B., Minugh-Purvis, N., & Mitchell, M. A.
- Affiliations
- University of Pennsylvania (US)
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Stedman, Hansell H.
- Venue
- Nature
- Published
- 2004-03-25
- Volume
- 428
- Issue
- 6981
- Pages
- 415-418
- ISSN
- 1465-7392 (ISSN-L)
- 0028-0836
- 1476-4679
- OpenAlex
- W2009692755
- Cited by
- 398
- References
- 1
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 20 · 2023: 15 · 2022: 10 · 2021: 13 · 2020: 13 · 2019: 10 · 2018: 15 · 2017: 14 · 2016: 22 · 2015: 12 · 2014: 22 · 2013: 19 · 2012: 17
- FWCI
- 142.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- University of Pennsylvania
- University of Washington
- Topics
- Social Sciences › Anthropology › Pleistocene-Era Hominins and Archaeology
- Physical Sciences › Earth and Planetary Sciences › Paleontology › Evolution and Paleontology Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- myosin heavy chain, MYH gene, frameshift mutation, masticatory muscles, hominin evolution, encephalization, human-chimpanzee divergence, molecular clock, muscle fiber size, Hominidae, Australopithecus, Paranthropus, Homo
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Pan troglodytes, Dogs, Exons, Fossils, Humans, Macaca, Masticatory Muscles, Molecular Sequence Data, Myosins, Phylogeny, Pongo pygmaeus, Skull, Time Factors, Hominidae, Frameshift Mutation, Myosin Heavy Chains, Evolution, Molecular, Computational Biology, History, Ancient
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