Here we explored the relationship between mortality and MHC genotype by comparing genotype frequencies in dead and live pups with those in adult seals. We find that one allele is a strong predictor of whether a pup is found dead or alive, while total MHC allele number exerts a strong influence on whether pups survive to enter the breeding population. Overall, the MHC appears to play a dominant role in dictating which animals are most likely to die and at what age.

Our results provide a remarkable example of how mortality in a large mammal can be highly non-random, instead being predictable from each individual's MHC genotype. The idea that upwards of 70% of grey seal mortality can be attributable to an individual's MHC genotype is truly remarkable and recalls the patterns reported for the Seychelles warbler2, an endangered passerine bird. However, the situation with the grey seals is arguably more extreme, in that the confidence intervals around the maximum difference between two survival curves of birds who carry one of several MHC alleles in a sample size of around 100 individuals are likely to be quite large. Moreover, our analysis is so far rather crude, in that we do not have adult age, measures of season quality or other parameters that the warbler study was able to fit. Regardless, it is interesting that these strong effects are both found in species with rather few MHC alleles who largely lack predators, suggesting that in such species disease plays a pivotal role in survival.

Our data imply contrasting mechanisms responsible for protecting pups against early mortality and for allowing successful recruitment into the breeding adult population. However, the exact mechanism remains unclear. One possibility is that grey seals face a small number of threats from key pathogens that impact on different parts of the life cycle and each of these is more likely to be overcome by possessing a different MHC allele. In this sense, pup mortality would be merely one of several challenges. Alternatively, after weaning there may be a range of pathogens, each of which tends to impact on a seal's physical condition, such that individuals with more MHC alleles are generally more healthy. We tend to favour a model based on one-to-one allele-pathogen interactions because the less-specific model would seem always to select for higher allelic diversity, which, based on other species, seems relatively easy to generate.

The low MHC allele diversity carried by grey seals rather belies the large effect size we report. A previous study has indicated a role for genome-wide heterozygosity in pre-weaning pup survival8, though compared with the MHC effects reported here, heterozygosity seems to exert a much smaller effect in pups and there is little evidence of an impact on pup to adult survival. Whether other components of the immune system are important remains to be seen, though our data suggest, compared with other species, that the MHC is relatively dominant in the grey seal. At the same time, low allele diversity suggests that the marine environment may limit the range of pathogens being faced4, making it relatively more important to carry the right alleles.

Previous studies have also highlighted unusual patterns of mate choice in grey seals. While behavioural observations suggest a classical polygynous mating system9, some individual females reveal evidence of mate fidelity10. At the same time, females who do not show mate fidelity appear to choose mates who are less genetically similar compared with previous partners11. Both strategies should help reduce the risk of inbreeding. However, if MHC allele number is so important in terms of survival, it would seem likely that mate choice in favour of MHC dissimilar partners would be present. This is clearly an interesting avenue for future research.

In conclusion, our results provide a strong support for the notion that the MHC gene complex can exert a major influence on survival. In line with studies showing that animals use olfactory clues associated with MHC genotype as a basis for mate choice12,13, it seems that female grey seals have much to gain from choosing MHC different males, since these will father pups who are more likely to survive to adulthood by dint of their increased MHC heterozygosity and greater chance of carrying allele 5.