title: 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.
authors.affiliation: Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. hstedman@mail.med.upenn.edu
authors.forename: Hansell H
authors.initials: HH
authors.lastname: Stedman
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Kozyak
authors.forename: Anthony
authors.initials: A
authors.lastname: Nelson
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Thesier
authors.forename: Leonard T
authors.initials: LT
authors.lastname: Su
authors.forename: David W
authors.initials: DW
authors.lastname: Low
authors.forename: Charles R
authors.initials: CR
authors.lastname: Bridges
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Shrager
authors.forename: Nancy
authors.initials: N
authors.lastname: Minugh-Purvis
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Mitchell
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019295:Computational Biology; D004285:Dogs; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D005580:Fossils; D016368:Frameshift Mutation / Q000235:genetics*; D049690:History, Ancient; D015186:Hominidae / Q000033:anatomy & histology* / Q000235:genetics*; D006801:Humans; D008251:Macaca / Q000033:anatomy & histology / Q000235:genetics; D008410:Masticatory Muscles / Q000033:anatomy & histology; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000235:genetics*; D009218:Myosins / Q000737:chemistry / Q000235:genetics*; D002679:Pan troglodytes / Q000033:anatomy & histology / Q000235:genetics; D010802:Phylogeny; D011148:Pongo pygmaeus / Q000033:anatomy & histology / Q000235:genetics; D012886:Skull / Q000033:anatomy & histology; D013997:Time Factors
chemical_list: C483469:MYH16 protein, human; D018995:Myosin Heavy Chains; D009218:Myosins