Skip to main content
Journal cover image

Ancient polymorphism and functional variation in the primate MHC-DQA1 5' cis-regulatory region.

Publication ,  Journal Article
Loisel, DA; Rockman, MV; Wray, GA; Altmann, J; Alberts, SC
Published in: Proceedings of the National Academy of Sciences of the United States of America
October 2006

Precise regulation of MHC gene expression is critical to vertebrate immune surveillance and response. Polymorphisms in the 5' proximal promoter region of the human class II gene HLA-DQA1 have been shown to influence its transcriptional regulation and may contribute to the pathogenesis of autoimmune diseases. We investigated the evolutionary history of this cis-regulatory region by sequencing the DQA1 5' proximal promoter region in eight nonhuman primate species. We observed unexpectedly high levels of sequence variation and multiple strong signatures of balancing selection in this region. Specifically, the considerable DQA1 promoter region diversity was characterized by abundant shared (or trans-species) polymorphism and a pronounced lack of fixed differences between species. The majority of transcription factor binding sites in the DQA1 promoter region were polymorphic within species, and these binding site polymorphisms were commonly shared among multiple species despite evidence for negative selection eliminating a significant fraction of binding site mutations. We assessed the functional consequences of intraspecific promoter region diversity using a cell line-based reporter assay and detected significant differences among baboon DQA1 promoter haplotypes in their ability to drive transcription in vitro. The functional differentiation of baboon promoter haplotypes, together with the significant deviations from neutral sequence evolution, suggests a role for balancing selection in the evolution of DQA1 transcriptional regulation in primates.

Duke Scholars

Published In

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

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

October 2006

Volume

103

Issue

44

Start / End Page

16331 / 16336

Related Subject Headings

  • Transcription, Genetic
  • Transcription Factors
  • Regulatory Sequences, Nucleic Acid
  • Protein Binding
  • Promoter Regions, Genetic
  • Primates
  • Polymorphism, Genetic
  • Phylogeny
  • Molecular Sequence Data
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Loisel, D. A., Rockman, M. V., Wray, G. A., Altmann, J., & Alberts, S. C. (2006). Ancient polymorphism and functional variation in the primate MHC-DQA1 5' cis-regulatory region. Proceedings of the National Academy of Sciences of the United States of America, 103(44), 16331–16336. https://doi.org/10.1073/pnas.0607662103
Loisel, Dagan A., Matthew V. Rockman, Gregory A. Wray, Jeanne Altmann, and Susan C. Alberts. “Ancient polymorphism and functional variation in the primate MHC-DQA1 5' cis-regulatory region.Proceedings of the National Academy of Sciences of the United States of America 103, no. 44 (October 2006): 16331–36. https://doi.org/10.1073/pnas.0607662103.
Loisel DA, Rockman MV, Wray GA, Altmann J, Alberts SC. Ancient polymorphism and functional variation in the primate MHC-DQA1 5' cis-regulatory region. Proceedings of the National Academy of Sciences of the United States of America. 2006 Oct;103(44):16331–6.
Loisel, Dagan A., et al. “Ancient polymorphism and functional variation in the primate MHC-DQA1 5' cis-regulatory region.Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 44, Oct. 2006, pp. 16331–36. Epmc, doi:10.1073/pnas.0607662103.
Loisel DA, Rockman MV, Wray GA, Altmann J, Alberts SC. Ancient polymorphism and functional variation in the primate MHC-DQA1 5' cis-regulatory region. Proceedings of the National Academy of Sciences of the United States of America. 2006 Oct;103(44):16331–16336.
Journal cover image

Published In

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

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

October 2006

Volume

103

Issue

44

Start / End Page

16331 / 16336

Related Subject Headings

  • Transcription, Genetic
  • Transcription Factors
  • Regulatory Sequences, Nucleic Acid
  • Protein Binding
  • Promoter Regions, Genetic
  • Primates
  • Polymorphism, Genetic
  • Phylogeny
  • Molecular Sequence Data
  • Humans