Trends in Immunology
Volume 26, Issue 9, September 2005, Pages 496-502
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Female choice and the MHC

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In animals, it is the female that typically selects a mating partner. This decision can occur before, during and after copulation. Here, recent evidence for the involvement of genes within the MHC in female choice is reviewed and the roles of MHC I and II antigens, various types of chemoreceptors, as well as MHC-encoded transcription factors, in securing an optimal genetic constitution of the offspring are discussed. Some particularly interesting and as yet unanswered questions are raised and some experiments that could provide deeper insight into the molecular mechanisms underlying female choice are suggested.

Introduction

Following the 1976 discovery by Yamazaki and colleagues that MHC-dependent, individual-specific odours influence sexual selection in mice [1], several studies in vertebrates, including humans, have revealed that highly polymorphic genes within the MHC participate in mate choice [2]. Therefore, besides their crucial function in adaptive and innate immune responses, the products of MHC genes also have a role in behavioural contexts 3, 4, as well as in reproduction. A detailed insight into the structure–function relationships of many molecules involved in immune reactions has already been achieved, however, only limited knowledge regarding the chemical nature of MHC-dependent odours, their recognition by chemoreceptors and how ligand–receptor interactions lead to neuronal responses and finally to MHC-influenced behaviours has been obtained. This deficit is probably a result of the complexity of the problem, which can be tackled only by a multi-disciplinary approach, involving, for example, studies of behaviour, genetics, immunology, neurobiology, chemistry and structural biology.

The connection between the MHC and mate selection is presumably a consequence of the crucial importance of the MHC in immune responses, in which two classes of genotypes might be favoured: heterozygotes and rare alleles 2, 5, 6, 7. MHC heterozygotes have an advantage over homozygotes because more peptides can be presented to T cells and rare MHC alleles might prevent pathogen evasion of host immune responses or exhibit a lack of association with autoimmunity, which has been shown by studies in a few vertebrate species, including humans 8, 9, 10. These two mechanisms could select for MHC diversity but both would also lead to the evolution of preferences for mates that are MHC heterozygous and MHC distinct [5]. The avoidance of inbreeding is an added benefit that can be a consequence of choosing an MHC-heterozygous mating partner. There is also evidence that MHC heterozygosity can aid in the recognition of kin [5]. For example, in the males of many mammalian species, this leads to the avoidance of mating with their own mother [4]. Theoretical considerations indicate that, for a given individual, an optimal number of MHC alleles at an intermediate level of MHC diversity exists [11]. Recent experimental evidence supports this prediction 8, 9.

In Darwin's view, sexual selection was restricted to the precopulatory phase, during which ‘the females…select the more agreeable partners’ [12]. However, within the last three decades, has come the realization that female choice (see Glossary) operates during and after copulation as well, and it influences the behaviour, anatomy and physiology of both sexes. Evidence from diverse animal groups also indicates that females use extra-pair matings to enhance the heterozygosity and fitness of their offspring 13, 14. Sperm competition, originally defined as the competition between spermatozoa of two or more males to fertilize a given set of oocytes, might also be connected with female choice 13, 14, 15.

We have only begun recently to understand some of the mechanisms that influence mate choice in vertebrates. This has been aided greatly by the molecular identification of odorant receptors (ORs) by Buck and Axel in 1991 [16] and the subsequent description of chemoreceptors (the vomeronasal receptors V1R and V2R) expressed within the vomeronasal organ (VNO) (reviewed in Ref. [17]). In addition, these different types of chemoreceptors not only fulfil their role of recognizing distinct ligands within the nose (an important process in the initial encounter of potential partners) but are also used by spermatozoa as guidance cues 18, 19. Possibly, their expression on spermatozoa enables a female to influence sperm motility through the establishment of chemical gradients within her reproductive tract. This indicates that postcopulatory female choice might involve gene products that take part in precopulatory mating decisions as well.

This review will focus on the evidence for the involvement of polymorphic MHC genes and chemoreceptors [17] in the various stages of female choice. The role of MHC-encoded transcription factors (TFs) that might influence prezygotic control within the fertilized oocyte will then be discussed, and analogies to mechanisms that participate in mate choice in fungi, currently one of the genetically best characterized systems [20], will be pointed out.

Section snippets

Precopulatory sexual selection

Circumstantial evidence for an influence of MHC alleles on precopulatory female choice has been observed in nearly all classes of vertebrates. However, evidence for a relationship among various receptors within the main olfactory epithelium (MOE) or the VNO (Box 1), the MHC and reproductive behaviours has been obtained only in a limited number of species, particularly rodents 21, 22 (for a comprehensive review of earlier work, including that carried out with rats, see Ref. [2]). The involvement

Postcopulatory sexual selection before oocyte fertilization

As a costly investment into an embryo with potentially suboptimal genetic and immunological properties should be avoided by a female, it would seem to make sense for her to scrutinize the suitability of the genetic contribution of the male before zygote formation. This could occur by cryptic female choice in connection with sperm competition, as well as by prezygotic female choice during and after fertilization of the oocyte (see the next section). The term ‘cryptic female choice’ refers to the

Postcopulatory sexual selection during and after oocyte fertilization

The interaction of male gametes with an oocyte depends on co-evolving proteins that are present on both types of cells [50]. In vertebrates, none of the proteins involved are known to be MHC-encoded, although, similar to MHC antigens, several are highly polymorphic. This additional barrier to fertilization might participate in cryptic female choice and act on the few mammalian spermatozoa (in humans, maximally a few hundred) that reach the vicinity of an unfertilized oocyte. These

Concluding remarks

Clearly, MHC molecules have a crucial role within the immune system, however, there is also growing evidence for a role in the refinement and plasticity of neuronal connections [3] and during distinct phases of reproduction, as summarized here. Many genes that fulfil essential functions within these three systems are in tight linkage with the MHC 26, 55 and are subject to positive selection. For example, two HLA-linked OR genes, OR2W1 (olfactory receptor, family 2, subfamily W, member 1) and

Acknowledgements

We thank Stephan Beck, Manfred Milinski, Cordula Petter, Paula Stockley, Christian J. Thaler, Armin Volz, as well as three anonymous reviewers for constructive comments on the manuscript. Our work on MHC-linked OR genes is financially supported by the Volkswagen-Stiftung (I75/196, I72/740) and the Monika-Kutzner-Stiftung, Berlin.

Glossary

Cryptic female choice:
Possibility that sexual selection might involve hidden female effects that impact on the success of males in fertilizing ova.
Female choice:
Selection of a mating partner by a female. This can occur before, during and after copulation.
Haplotype:
Combination of alleles at several loci on a single chromosome of a given individual. For example, for a gene with alleles W and w that is linked to another locus with alleles V and v, possible haplotypes are WV, Wv, wV and wv.

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