Balancing selection and the maintenance of MHC supertype variation in a selfing vertebrate.

Despite being probably one of the most studied topics in Evolutionary Biology, the mechanisms of maintenance of major histocompatibility complex (MHC) diversity in vertebrates remain also one of the most debated topics [1]. Ellison et al. [2] studied MHC class I diversity of a selfing Kryptolebias marmoratus population by clustering alleles in supertypes grouped by their physico-chemical similarity, and suggested that the maintenance of highly divergent MHC supertypes despite the loss of diversity after several generations of selfing could be due to overdominance. van Oosterhout [3] presented an intriguing alternative explanation to overdominant selection, according to which diversity could be preserved in the form of divergent supertypes at different loci, provided alleles from different supertypes segregate at different loci. This view would provide a simple explanation for the maintenance of divergent supertypes without the need to invoke overdominance, and would imply that balancing selection acts at the supertype level, instead of acting upon loci variation. However, such an explanation does not necessarily rule out the hypothesis of overdominance. One of the arguments against the overdominant scenario is the potentially high loading cost associated with the maintenance of heterozygosity at the 13 MHC class I loci that had previously been identified by Sato et al. [4] in this species. Although 13 loci had been identified in populations from three different geographical origins, only a maximum of six different loci were present per population [4]. A similar result (maximum five loci per population) was obtained by Fisher [5] in a screening of two different K. marmoratus populations. Ellison et al. [2] did not identify individual loci, but found a maximum of 11 alleles per individual and most importantly, found that MHC variability was closely associated with microsatellite heterozygosity. Thus, individuals with nine, ten and eleven MHC alleles displayed heterozygos-ities of 0.56, 0.67 and 0.78, respectively for a set of 32 microsatellites. This level of heterozygosity is unusually high for a selfing species, and may suggest that those individuals were the product of recent outcrossing between selfing lines [6]. Thus, given that MHC class I heterozygosity has been reported to be higher than that of microsatellites [4], the results of Ellison et al. [2] also suggest a maximum of 5–6 MHC class I loci per population. Therefore, alleles from different supertypes could potentially correspond to the same locus as it happens, for example, in humans where the three class I HLA loci (A, …