MHC and Captive Breeding: A Rebuttal

In a recent Comment (Conservation Biology 5(2):249251), Austin Hughes advocated a "radical reorientation of all captive breeding programs." His suggestion is that the major goal of captive breeding programs should be to maintain an even distribution of MHC "alleles" in a captive population. This will, he points out, result in a skewed distribution away from an equal representation of founders, with concomitant increased inbreeding. That is, Hughes's strategy will entail greater loss of allelic diversity at other loci, but he dismisses these loci as neutral and unimportant. We agree that allelic diversity at the MHC locus is important and that Hughes's optimization ideas should not be summarily dismissed. However, we point out several errors in Hughes's analysis. First, he has grossly miscalculated extinction probabilities for loss of alleles under genetic drift. For example, he says that for N, = 200, the chance of fixing in 20 generations an allele initially at 90% frequency is 0.85. We calculate this probability as 0.03. Possibly, Hughes has used an Ne of 20. In any case, he is exaggerating the problem of allele loss by at least an order of magnitude. In a related calculation, Hughes looks at the loss of heterozygosity in a triallelic locus and shows, correctly, that a 10% loss of heterozygosity can occur in different ways, one involving allele loss and others not. We point out that these cases are not, however, equally probable. We have calculated the extinction probability of an allele initially at frequency of 10% as 0.15 at the point in the process at which the population heterozygosity has dropped by 10%; thus, 85% of the time the allele would still be present in such a population, though of course not in the frequency at which it started. Second, Hughes dismisses as neutral the entire nonMHC fraction of the genome (see Comment by Vrijenhoek and Leberg 1991). He cavalierly banishes a great many genes in the process. The number of gene loci in vertebrates has been variously estimated, but a generally agreed-on number is approximately 100,000. The number of environments the gene products of these loci face may be considerably greater than that; Walter Gilbert (personal communication) has estimated that because of alternative splicing in different tissues the number of different gene products produced by the genome may be more like 106. There is no way of knowing at the moment whether a polymorphism that has no effect when it is expressed in one tissue might produce a selective differential when it is expressed in another, but it does not seem unreasonable to expect this to happen occasionally. While it is also dangerous to extend to the entire genome estimates of the number of loci that carry nonsynonymous substitutions at appreciable frequency, judging by the data from soluble enzymes and blood groups it appears that about a third of them do. Let us suppose that in only 1% of these 3 x 105 potentially selective situations the polymorphic loci are selectively maintained. This is still 3000 loci, only a tiny fraction of which are known. MHC is the one we are currently aware of that is most obviously subject to balancing selection, but it verges on hubris to suggest that there may not be others equally or more important. Consider the A and B alleles at the ABO locus, which differ by four amino acids and specify very different glycosyltransferase activities (Yamamoto et al. 1990); these alleles, which have persisted for long periods of evolutionary time, appear unlikely to be neutral. Consider also the Rh