ArticleProceedings of the National Academy of Sciences of the United States of America2006
Ancient polymorphism and functional variation in the primate MHC-DQA1 5' cis-regulatory region.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 63 citations in OpenAlex.
- Divergent cis-regulatory haplotypes at Tlr2 are associated with immune responsiveness.Molecular biology and evolution · 2026Article
- Article
- Comparative three-dimensional genome architectures of adipose tissues provide insight into human-specific regulation of metabolic homeostasis.The Journal of biological chemistry · 2023Article
- HLA-DRB1 genes and the expression dynamics of HLA CIITA determine the susceptibility to T2DM.Immunogenetics · 2021Article
- Reorganization of 3D genome structure may contribute to gene regulatory evolution in primates.PLoS genetics · 2019Article
- Negative Frequency-Dependent Selection Is Frequently Confounding.Frontiers in ecology and evolution · 2018Article
- Cis-regulatory evolution in a wild primate: Infection-associated genetic variation drives differential expression of MHC-DQA1 in vitro.Molecular ecology · 2017Article
- A time transect of exomes from a Native American population before and after European contact.Nature communications · 2016Article
- Identification of Multiple Forms of RNA Transcripts Associated with Human-Specific Retrotransposed Gene Copies.Genome biology and evolution · 2016Article
- Recent Selection Changes in Human Genes under Long-Term Balancing Selection.Molecular biology and evolution · 2016Article
- Next-generation genotyping of hypervariable loci in many individuals of a non-model species: technical and theoretical implications.BMC genomics · 2016Article
- Trans-species polymorphism in humans and the great apes is generally maintained by balancing selection that modulates the host immune response.Human genomics · 2015Review
- Trans-Species Polymorphism in Immune Genes: General Pattern or MHC-Restricted Phenomenon?Journal of immunology research · 2015Review
- Epigenetic modifications are associated with inter-species gene expression variation in primates.Genome biology · 2014Article
- The functional importance of sequence versus expression variability of MHC alleles in parasite resistance.Genetica · 2012Article
- Article
- Balancing selection is common in the extended MHC region but most alleles with opposite risk profile for autoimmune diseases are neutrally evolving.BMC evolutionary biology · 2011Article
- Gene expression differences among primates are associated with changes in a histone epigenetic modification.Genetics · 2011Article
- A genome-wide study of DNA methylation patterns and gene expression levels in multiple human and chimpanzee tissues.PLoS genetics · 2011Article
- HLA-DRB1 may be antagonistically regulated by the coordinately evolved promoter and 3'-UTR under stabilizing selection.PloS one · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.