This approach cannot be used in the case of small-scale recombination. If these sites are nonsynonymous, such a cluster might result from convergent evolution at the amino acid level, rather than recombination. Thus, this method cannot always discriminate between the hypotheses of recombination and gene conversion. Although it may be difficult to decide in some specific cases whether or not interallelic recombination has been involved, studies employing a variety of methods have been able to detect major trends. One type of trend that has been observed is a difference between loci.
Some evidence favors the latter hypothesis.
First, putative recombination events that have occurred at human class I loci disproportionately involve the PBR codons, as is consistent with their being selectively favored. In introns, recombination breaks up linkage of intron sites with nonsynonymous PBR sites that are under balancing selection, thus allowing genetic drift to reduce sequence diversity in introns. In exons, polymorphism has been selectively favored, evidently because of the wide immune surveillance of heterozygotes, and over time this selection has given rise to numerous quite distinct alleles. So far, the levels of recombination at MHC class II loci have not been studied as extensively as those at class I loci. We developed a simple method to address this problem.