Stem-loop potential in MHC genes: A new way of evaluating positive Darwinian selection?

The domains of polymorphic major histocompatibility complex (MHC) proteins which interact with peptides and T-cell receptors are considered to have been under positive evolutionary selection pressure. Evidence for this is a high ratio of non-synonymous to synonymous mutations in the corresponding genomic domains. By this criterion snake venom phospholipase A(2) genes have also been under positive selection pressure. Recent studies of the latter genes indicate that positive selection has overridden an evolutionary pressure on base order which normally promotes the potential to extrude single-strand stem-loops from supercoiled duplex DNA (''fold pressure''). This has resulted in base order-dependent stem-loop potential being shifted to introns, which are highly conserved between species. It is now shown that, like snake venom phospholipase A(2) genes, the domains of polymorphic MHC genes which appear to have responded to positive selection pressure have decreased base order-dependent stem-loop potential. The evolutionary pressure to generate stem-loop potential (believed to be important for recombination) has been overridden less in exons under negative purifying selection than in exons under positive Darwinian selection. Thus, base order-dependent stem-loop potential shows promise as an independent indicator of positive selection.