title: HLA-H: a pseudogene with increased variation due to balancing selection at neighboring loci.
abstract: The HLA complex includes the most polymorphic genes in the human genome. However, the HLA class Ib loci have little, if any, nucleotide variation, presumably due to their specialized functions or perhaps due to a lack of function. This population genetic study of HLA-H, a class I pseudogene, was initiated to determine the pattern of variation at neutral sites within the HLA complex. We found that the pattern of variation for HLA-H is consistent with the neutral model. However, the amount of variation in HLA-H is significantly greater than estimates for other silent sites within the human genome outside of the MHC (theta = 0.0144, P < 0.000001). Our study further indicates that other possible causes of increased variation such as a high mutation rate for HLA-H, interlocus gene conversion, increased diversity in the sample population in general, and selection acting directly on HLA-H are unlikely. Instead, these data suggest that HLA-H has increased variation as a result of balancing selection acting on nearby loci such as HLA-A.
authors.affiliation: Department of Human Genetics, University of Chicago, USA. cgrimsle@fred.fhcrc.org
authors.forename: C
authors.initials: C
authors.lastname: Grimsley
authors.forename: K A
authors.initials: KA
authors.lastname: Mather
authors.forename: C
authors.initials: C
authors.lastname: Ober
mesh_terms: D000818:Animals; D044383:Black People / Q000235:genetics; D002460:Cell Line; D017931:DNA Primers; D019143:Evolution, Molecular; D005091:Exons; D015894:Genome, Human; D006071:Gorilla gorilla / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007438:Introns; D008285:Major Histocompatibility Complex; D008565:Membrane Proteins; D019974:Pan paniscus / Q000235:genetics; D002679:Pan troglodytes / Q000235:genetics; D011110:Polymorphism, Genetic; D011148:Pongo pygmaeus / Q000235:genetics; D011544:Pseudogenes; D012641:Selection, Genetic
chemical_list: D017931:DNA Primers; C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins