At the molecular level, we found that the European American couples we studied are significantly more MHC-dissimilar than random pairs of individuals, and that this pattern of dissimilarity is extreme when compared to the rest of the genome, both globally and when broken into windows having the same length and recombination rate as the MHC. Our analyses based on HLA types also show a signature of dissimilarity between spouses. Such dissimilarity, observed from both molecular and serological data, cannot be explained by demographic processes, since such effects would affect the whole genome. On the other hand, this MHC dissimilarity could result from pressure for disassortative mating at the MHC level. Such a mechanism could be triggered by our olfactory capacity for discriminating MHC-mediated odour types 
. Alternatively, this genetic dissimilarity could result from selection of the spermatozoa by the female oocyte (post-copulatory sexual selection), a further safeguard favouring the production of MHC-heterozygous offspring more resistant to pathogens see 
for reviews. Indeed, all studied couples were selected for having offspring, and the excess of dissimilarity observed could be restricted to fertile couples, rather than couples in general. However, further analysis showed that the offspring of these couples were not more MHC-diverse than expected by random selection of parental gametes (results not shown). Moreover, our results in European American couples reinforce previous evidence of MHC-disassortative mating among Hutterite couples 
, in which all couples were included, regardless of whether they had a child (C. Ober, personal communication). Like the Ober study, the sampled couples in our study are from a cultural isolate (in our case sampled from the Mormon community), so one might speculate that MHC-based mate choice is stronger or easier to detect in settings where there is less heterogeneity in other factors which influence mate choice, but the current absence of detailed molecular studies of mate choice in other human populations makes this impossible to assess. The two studies in Swiss males and females showing a significant preference of females for the odor of MHC-dissimilar (over MHC-similar) males 
implicate one possible mechanism by which couples may implement MHC-dependent mate choice. Taken together, these results strengthen the hypothesis that MHC genetic variation influences mate choice in some human populations.
Our analyses of the European American sample also show that the results based on molecular data were more significant than those based on HLA types. Although we cannot rule out power effects in explaining such a difference, it seems plausible, and consistent with our data, that the biological mechanisms involved in disassortative mating would depend on the MHC in ways that are not simply captured by HLA types. Such biological mechanisms could possibly result from a summation of effects over multiple genes, and not only from the six HLA genes studied here.
On the other hand, Yoruba couples exhibited a significant genome-wide signature of assortative mating, which is likely to result from socio-demographic processes specific to this population. The Yoruba are still organized in paternal lineages, which are exogamous units 
and C. Adebamowo, personal communication. Although we do not have specific ethnological data collected with the Yoruba samples to explain our observations, a process in which matrimonial exchanges between genealogically related lineages are more frequent than matrimonial exchanges between genealogically unrelated lineages could have left such a genome-wide signature. On the contrary, for the MHC region, no significant pattern of similarity/dissimilarity was observed, at either the molecular level or the serological level. Several hypotheses can be proposed to explain this observation: firstly, it is possible either that the MHC is not involved in mate choice in this population, or that social factors are relatively more important than the MHC and that the sample size here does not allow detection of MHC effect on mate choice. Secondly, it is possible that MHC-based mate choice is aiming for an optimal, rather than maximal, number of MHC alleles previous theoretical and experimental evidence for this hypothesis are reviewed in 
. Such a mechanism would explain why evidence of disassortative mating was found in the European Americans, all sampled in the Mormon community exhibiting a relatively low SNP diversity in the MHC (0.349), as well as in the genetically isolated Hutterite community 
, but not in Yoruba. Indeed, the Yoruba exhibit a relatively higher SNP diversity in the MHC (0.366) than the European American, and the optimization of the number of HLA alleles in Yoruba may involve mating with a not-so-MHC-dissimilar individual. This hypothesis is also consistent with the “sweaty T-shirts” experiment performed between females and males from different ethnicities (thus having a higher range of MHC dissimilarity than males and females coming from the same community) and showing that females prefer the odor of males with little MHC-dissimilarity than the odor of males with more extreme MHC-dissimilarity 
. Finally, it is possible that in African populations, individuals carrying pathogen-resistant alleles are easier to identify than elsewhere, because of the higher pathogen pressure. In such conditions, it is possible that mating preferences for particular pathogen-resistant MHC alleles are stronger than mating preferences for MHC-dissimilarity per se 
In conclusion, our study, based on a large number of molecular markers which allow us to control for genome wide effects, indicates a clear-cut signature of MHC-disassortative mating in a sample of European American couples. This supports the existence of MHC-related biological factors contributing to mate choice in at least some human populations. On the other hand, the Yoruba exhibit a genome-wide tendency for enhanced similarity among couples but no significant pattern at the MHC level. This suggests that socio-demographic factors may be more important than biological factors for mate choice in this population, although the existence of MHC-dependent mate choice in Yoruba, aimed at optimizing (rather than maximizing) the number of HLA alleles in the offspring, cannot be excluded. Our study indicates that the relative importance of biological and social factors varies from one population to another. It also highlights the need for the exploration of further genome-wide data in larger sample sizes, including “just married” childless couples, sampled in several ethnically differentiated groups, in order to build a more robust view of the biological determinants acting on mate choice in humans.