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Osteocalcin protein sequences of Neanderthals and modern primates

Nielsen-Marsh, C.M.; Richards, M.P.; Hauschka, P.V.; Thomas-Oates, J.E.; Trinkaus, E.; Pettitt, P.B.; Karavanic, I.; Poinar, H.; Collins, M.J.

Authors

C.M. Nielsen-Marsh

M.P. Richards

P.V. Hauschka

J.E. Thomas-Oates

E. Trinkaus

I. Karavanic

H. Poinar

M.J. Collins



Abstract

We report here protein sequences of fossil hominids, from two Neanderthals dating to ≈75,000 years old from Shanidar Cave in Iraq. These sequences, the oldest reported fossil primate protein sequences, are of bone osteocalcin, which was extracted and sequenced by using MALDI-TOF/TOF mass spectrometry. Through a combination of direct sequencing and peptide mass mapping, we determined that Neanderthals have an osteocalcin amino acid sequence that is identical to that of modern humans. We also report complete osteocalcin sequences for chimpanzee (Pan troglodytes) and gorilla (Gorilla gorilla gorilla) and a partial sequence for orangutan (Pongo pygmaeus), all of which are previously unreported. We found that the osteocalcin sequences of Neanderthals, modern human, chimpanzee, and orangutan are unusual among mammals in that the ninth amino acid is proline (Pro-9), whereas most species have hydroxyproline (Hyp-9). Posttranslational hydroxylation of Pro-9 in osteocalcin by prolyl-4-hydroxylase requires adequate concentrations of vitamin C (l-ascorbic acid), molecular O2, Fe2+, and 2-oxoglutarate, and also depends on enzyme recognition of the target proline substrate consensus sequence Leu-Gly-Ala-Pro-9-Ala-Pro-Tyr occurring in most mammals. In five species with Pro-9–Val-10, hydroxylation is blocked, whereas in gorilla there is a mixture of Pro-9 and Hyp-9. We suggest that the absence of hydroxylation of Pro-9 in Pan, Pongo, and Homo may reflect response to a selective pressure related to a decline in vitamin C in the diet during omnivorous dietary adaptation, either independently or through the common ancestor of these species.

Citation

Nielsen-Marsh, C., Richards, M., Hauschka, P., Thomas-Oates, J., Trinkaus, E., Pettitt, P., …Collins, M. (2005). Osteocalcin protein sequences of Neanderthals and modern primates. Proceedings of the National Academy of Sciences, 102(12), 4409-4413. https://doi.org/10.1073/pnas.0500450102

Journal Article Type Article
Publication Date Mar 1, 2005
Deposit Date Jul 14, 2009
Journal Proceedings of the National Academy of Sciences
Print ISSN 0027-8424
Electronic ISSN 1091-6490
Publisher National Academy of Sciences
Peer Reviewed Peer Reviewed
Volume 102
Issue 12
Pages 4409-4413
DOI https://doi.org/10.1073/pnas.0500450102
Public URL https://durham-repository.worktribe.com/output/1597988