Molecular Biology and Evolution, Vol 15, 1581-1588, Copyright © 1998 by Society for Molecular Biology and Evolution
C Grimsley, KA Mather and C Ober
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.
ORIGINAL ARTICLE
HLA-H: a pseudogene with increased variation due to balancing selection at neighboring loci
Department of Human Genetics, University of Chicago, USA. cgrimsle@fred.fhcrc.org
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