Is Mate Choice in Humans MHC-Dependent?
Raphae ¨lle Chaix1,2*, Chen Cao3, Peter Donnelly1,4
1Department of Statistics, University of Oxford, Oxford, United Kingdom, 2Unite ´ d’Eco-Anthropologie, CNRS UMR 5145, Muse ´e de l’Homme, Paris, France, 3CAS-MPG
Partner Institute for Computational Biology, Shanghai, China, 4The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
In several species, including rodents and fish, it has been shown that the Major Histocompatibility Complex (MHC)
influences mating preferences and, in some cases, that this may be mediated by preferences based on body odour. In
humans, the picture has been less clear. Several studies have reported a tendency for humans to prefer MHC-dissimilar
mates, a sexual selection that would favour the production of MHC-heterozygous offspring, who would be more resistant to
pathogens, but these results are unsupported by other studies. Here, we report analyses of genome-wide genotype data
(from the HapMap II dataset) and HLA types in African and European American couples to test whether humans tend to
choose MHC-dissimilar mates. In order to distinguish MHC-specific effects from genome-wide effects, the pattern of
similarity in the MHC region is compared to the pattern in the rest of the genome. African spouses show no significant
pattern of similarity/dissimilarity across the MHC region (relatedness coefficient, R=0.015, p=0.23), whereas across the
genome, they are more similar than random pairs of individuals (genome-wide R=0.00185, p,1023). We discuss several
explanations for these observations, including demographic effects. On the other hand, the sampled European American
couples are significantly more MHC-dissimilar than random pairs of individuals (R=20.043, p=0.015), and this pattern of
dissimilarity is extreme when compared to the rest of the genome, both globally (genome-wide R=20.00016, p=0.739)
and when broken into windows having the same length and recombination rate as the MHC (only nine genomic regions
exhibit a higher level of genetic dissimilarity between spouses than does the MHC). This study thus supports the hypothesis
that the MHC influences mate choice in some human populations.
Citation: Chaix R, Cao C, Donnelly P (2008) Is Mate Choice in Humans MHC-Dependent?. PLoS Genet 4(9): e1000184. doi:10.1371/journal.pgen.1000184
Editor: Molly Przeworski, University of Chicago, United States of America
Received February 25, 2008; Accepted July 30, 2008; Published September 12, 2008
Copyright: ? 2008 Chaix et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: R. Chaix was funded by a postdoctoral fellowhip from EMBO. C. Cao was funded by the Chinese Academy of Sciences and Max Planck Society. P.
Donnelly was supported by the Wellcome Trust and the Wolfson Foundation.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: email@example.com
In vertebrates, several studies have revealed that highly
polymorphic genes within the Major Histocompatibility Complex
(MHC) may have a role in mate choice. In particular, it has been
shown that MHC genes influence individual body odor in mice and
rats [1–7] and that mice prefer MHC-dissimilar mates e.g. [8–11],
and  for a review. Evidence for MHC-disassortative mating was
also found in sand lizards . Studies in fish (and in particular
Arctic charr) have shown their ability to discriminate the odors of
similar and dissimilar MHC siblings , and shown that salmon
prefer MHC dissimilar mates  while female sticklebacks choose
a mate in order to complement their own set of MHC genes and to
optimize the number of different alleles in their offspring .
Complex MHC-based mate choice was also observed in birds
[17,18]. The MHC is the most important part of the genome with
respect to immunity  and such MHC-based mate choice could
increase or optimize the number of non-self antigens that future
offspring can recognize and thus increase their resistance to
pathogens [12,20,21]. It could also have contributed to the
extraordinary polymorphism observed at MHC loci .
On the other hand, in humans, the role of the MHC in mate
choice is very controversial. Ober et al studied classical HLA types
for 400 couples from the Hutterite community and found
significantly fewer HLA matches between husbands and wives
than expected when taking into account the social structure of
Hutterites . On the other hand, no evidence of MHC-based
mate choice was found in a study of 200 couples from South
Amerindian tribes . In a less direct way, other studies have
focused on odor preferences: in ‘‘sweaty T-shirts experiments’’, in
which females were asked to smell T-shirts worn by different
males, it was shown that females significantly prefer the odor of T-
shirts worn by MHC-dissimilar males, although such preference
was not found among females taking the contraceptive pill [24,25].
However, in another sweaty T-shirts experiment, in which males
where chosen from a different ethnicity from the females and
females were not aware of the nature of the smell (contrary to the
two previous studies), females significantly preferred the odor of
males having a small number of HLA alleles matching their
paternal inherited alleles than the odor of males having fewer
matches . Although it has not been established that odor
preference is a key factor in mate choice, such studies support the
hypothesis that humans are able to discriminate MHC types of
potential mates through odor cues and that humans may use such
information when choosing a mate. However, the lack of
congruence between these studies means that there is still
uncertainty as to whether MHC variation influences mate choice
in humans, and to what extent. The availability of genetic
variation data at genomic scales now allows careful assessment of
this question. Crucially, it allows us to distinguish MHC-specific
effects from genome-wide effects.
In this study, we tested the existence of MHC-disassortative
mating in humans by directly measuring the genetic similarity at
the MHC level between spouses. These data were extracted from
PLoS Genetics | www.plosgenetics.org1September 2008 | Volume 4 | Issue 9 | e1000184