English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution

Chou, H. H., Hayakawa, T., Diaz, S., Krings, M., Indriati, E., Leakey, M., et al. (2002). Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution. Proceedings of the National Academy of Sciences of the United States of America, 99(18), 11736-11741. doi:10.1073/pnas.182257399.

Item is

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Chou, H. H., Author
Hayakawa, Toshiyuki, Author
Diaz, S., Author
Krings, Matthias1, Author           
Indriati, E., Author
Leakey, M., Author
Pääbo, Svante1, Author                 
Satta, Y., Author
Takahata, N., Author
Varki, Ajit, Author
Affiliations:
1Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society, ou_1497672              

Content

show
hide
Free keywords: hominid evolution; sialic acids; Alu sequences
 Abstract: Humans are genetically deficient in the common mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc) because of an Alu- mediated inactivating mutation of the gene encoding the enzyme CMP-N-acetylneuraminic acid (CMP-Neu5Ac) hydroxylase (CMAH). This mutation occurred after our last common ancestor with bonobos and chimpanzees, and before the origin of present-day humans. Here, we take multiple approaches to estimate the timing of this mutation in relationship to human evolutionary history. First, we have developed a method to extract and identify sialic acids from bones and bony fossils. Two Neandertal fossils studied had clearly detectable Neu5Ac but no Neu5Gc, indicating that the CMAH mutation predated the common ancestor of humans and Neandertals, approximate to0.5-0.6 million years ago (mya). Second, we date the insertion event of the inactivating human-specific sahAluY element that replaced the ancestral AluSq element found adjacent to exon 6 of the CMAH gene in the chimpanzee genome. Assuming Alu source genes based on a phylogenetic tree of human-specific Alu elements, we estimate the sahAluY insertion time at approximate to2.7 mya. Third, we apply molecular clock analysis to chimpanzee and other great ape CMAH genes and the corresponding human pseudogene to estimate an inactivation time of approximate to2.8 mya. Taken together, these studies indicate that the CMAH gene was inactivated shortly before the time when brain expansion began in humankind's ancestry, approximate to2.1-2.2 mya. In this regard, it is of interest that although Neu5Gc is the major sialic acid in most organs of the chimpanzee, its expression is selectively down-regulated in the brain, for as yet unknown reasons.

Details

show
hide
Language(s): eng - English
 Dates: 2002-09-03
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 18656
DOI: 10.1073/pnas.182257399
ISI: 000177843100038
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Proceedings of the National Academy of Sciences of the United States of America
  Alternative Title : Proc. Natl. Acad. Sci. U. S. A.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 99 (18) Sequence Number: - Start / End Page: 11736 - 11741 Identifier: ISSN: 0027-8424