Wellcome Images mice In this series of posts looking at the evolutionary reasons for the extraordinary diversity of the major histocompatibility complex, I’ve already talked about two mechanisms that are probably not involved: Increased mutation frequency, and maternal-fetal interactions. A third mechanism that’s been proposed is sexual selection. It’s probably not a major player either, but it may contribute some to the diversity.

(I should preface this by pointing out that I’m not even close to being an evolutionary biologist. If anyone wants to correct me or clarify something, please do.)

I can separate this into two questions: (1) Is there sexual selection based on MHC? (2) If so, why?

Overall, the data mostly support the idea that at least sometimes, in some species, MHC is a factor in mate choice. The most famous experiments are those in mice, starting in 1976 with Yamazaki’s paper “Control of mating preferences in mice by genes in the major histocompatibility complex”1 and followed up with a bunch of repeats and variations.2 One of the the most striking of the followups3 concluded that “MHC-based mating prefences are a major force responsible for the maintenance of MHC genetic diversity in Mus.

But “a lack of repeatability of several studies, and an apparent plasticity in response across experiments, questioned the robustness of the data, and the general relevance of mate choice as a primary driver of MHC diversity“:4

  • Most groups find a relatively weak effect
  • Some groups find no effect at all
  • And apparently in at least one strain of mice the effect is reversed, so that the selection is for homogeneity.

SticklebackAttempts to resolve this have turned to other species. The work on humans has really been pretty crap, as far as I can tell, and inconclusive anyway. People have looked at various mammals, birds, fish (especially sticklebacks, but others as well), lizards, and so on, and have returned with evidence pointing both ways.5 (Of course, there’s no guarantee that every species has the same mechanism or the same requirements though, since MHC diversity is pretty much universal, it’s simplest to assume that there are universal reasons underlying it, too.) Overall, the literature has lots of smoke, but there is probably some fire in it as well.

As an interesting side note: Where there is an effect seen it’s generally agreed that the selection is performed by odor — detection of MHC type by smell. This is the traditional explanation for the mouse phenomenon, and a recent example of this was in sticklebacks:

Our results suggest that odor-based evaluation of prospective mates is an evolutionarily ancient component of MHC-related sexual selection strategies, designed to achieve an optimal degree of MHC diversity in offspring.6

The neat thing about this is that, relatively recently, a non-classical MHC class I family has been implicated in odor detection. I want to talk more about that some other time, so that’s a teaser, I guess.

Accepting that there is some MHC-based mate choice, the next question is, Why? What makes selecting mates based on MHC type an advantage? There are two general classes of answers: Either it’s directly because of MHC, or else the MHC is a useful marker for outbreeding:

The concept that MHC genes could be intimately linked with sexual behaviour and mate choice has been intuitively attractive given that the primary function of the MHC is to distinguish self from non-self at the cellular level, and so could also underpin a mechanism that distinguishes relatives from non-relatives at an organismal level. Moreover, the complex architecture and high polymorphism inherent in the MHC provides the variability necessary for a genetically based recognition system.7

Or, of course, both are possible — they’re not mutually exclusive. What’s more, different forms of selection may likely act at different points in a species’ existence: there may be a period of strong parasite pressure, say, followed by generations with minimal parasitism to deal with during which mate choice maintains the diversity.

To the extent that there’s any consensus on this, the general sense is that any MHC-based selection is directly based on the fitness associated with MHC — choosing a mate to keep their MHC from becoming homozygous — rather than purely as an inbreeding-prevention mechanism. If so, then sexual selection may be a mechanism for keeping MHC diverse, but doesn’t really answer the original question of “why” MHC is so diverse.

There are two remaining major possible explanations for that.


  1. Yamazaki, K., Boyse, E. A., Mike, V., Thaler, H. T., Mathieson, B. J., Abbott, J., Boyse, J., Zayas, Z. A., and Thomas, L. (1976). Control of mating preferences in mice by genes in the major histocompatibility complex. J Exp Med 144, 1324-1335.[]
  2. Reviewed in Jordan, W. C., and Bruford, M. W. (1998). New perspectives on mate choice and the MHC. Heredity 81, 127-133. and Arcaro, K. F., and Eklund, A. (1998). A review of MHC-based mate preferences and fostering experiments in two congenic strains of mice. Genetica 104, 241-244. []
  3. Potts, W. K., Manning, C. J., and Wakeland, E. K. 1991. Mating patterns in seminatural populations of mice influenced by MHC genotype. Nature 352, 619-621. []
  4. Piertney, S. B., and Oliver, M. K. (2006). The evolutionary ecology of the major histocompatibility complex. Heredity 96, 7-21. []
  5. Summarized in the Piertney and Oliver review. []
  6. Milinski, M., Griffiths, S., Wegner, K. M., Reusch, T. B., Haas-Assenbaum, A., and Boehm, T. (2005). Mate choice decisions of stickleback females predictably modified by MHC peptide ligands. Proc Natl Acad Sci U S A 102, 4414-4418. []
  7. Piertney, S. B., and Oliver, M. K. (2006). The evolutionary ecology of the major histocompatibility complex. Heredity 96, 7-21. []