Osteocalcin protein sequences of Neanderthals and modern primates

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

doi:10.1073/pnas.0500450102

Osteocalcin protein sequences of Neanderthals and modern primates

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

Research output: Contribution to journal › Article › peer-review

Abstract

We report here protein sequences of fossil hominids, from two Neanderthals dating to approximate 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 O-2, 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.

Original language	English
Pages (from-to)	4409-4413
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	102
Issue number	12
DOIs	https://doi.org/10.1073/pnas.0500450102
Publication status	Published - 22 Mar 2005

Bibliographical note

Keywords

MALDI-TOF/TOF
dietary adaptation
biomolecular preservation
vitamin C
evolution
GLA PROTEIN
BONE
COLLAGEN
HIF
RECOGNITION
COMPLEX
MODIFY
FAMILY
MOUSE
RAT

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10.1073/pnas.0500450102

Nielsen-Marsh_PNAS_2005.pdf

http://www.pnas.org/cgi/content/abstract/0500450102v1

Cite this

@article{38f543ec8f73477aa6bbd62d1b55d37b,

title = "Osteocalcin protein sequences of Neanderthals and modern primates",

abstract = "We report here protein sequences of fossil hominids, from two Neanderthals dating to approximate 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 O-2, 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.",

keywords = "MALDI-TOF/TOF, dietary adaptation, biomolecular preservation, vitamin C, evolution, GLA PROTEIN, BONE, COLLAGEN, HIF, RECOGNITION, COMPLEX, MODIFY, FAMILY, MOUSE, RAT",

author = "Nielsen-Marsh, {C M} and Richards, {M P} and Hauschka, {P V} and Thomas-Oates, {J E} and E Trinkaus and Pettitt, {P B} and I Karavanic and H Poinar and Collins, {Matthew James}",

note = "Copyright {\textcopyright} 2005 by the National Academy of Sciences. Published online before print March 7, 2005, 10.1073/pnas.0500450102",

year = "2005",

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language = "English",

volume = "102",

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T1 - Osteocalcin protein sequences of Neanderthals and modern primates

AU - Nielsen-Marsh, C M

AU - Richards, M P

AU - Hauschka, P V

AU - Thomas-Oates, J E

AU - Trinkaus, E

AU - Pettitt, P B

AU - Karavanic, I

AU - Poinar, H

AU - Collins, Matthew James

PY - 2005/3/22

Y1 - 2005/3/22

N2 - We report here protein sequences of fossil hominids, from two Neanderthals dating to approximate 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 O-2, 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.

AB - We report here protein sequences of fossil hominids, from two Neanderthals dating to approximate 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 O-2, 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.

KW - MALDI-TOF/TOF

KW - dietary adaptation

KW - biomolecular preservation

KW - vitamin C

KW - evolution

KW - GLA PROTEIN

KW - BONE

KW - COLLAGEN

KW - HIF

KW - RECOGNITION

KW - COMPLEX

KW - MODIFY

KW - FAMILY

KW - MOUSE

KW - RAT

U2 - 10.1073/pnas.0500450102

DO - 10.1073/pnas.0500450102

M3 - Article

SN - 0027-8424

VL - 102

SP - 4409

EP - 4413

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 12

ER -