The evolutionary construction of molecular polymorphisms

Abstract

Simple evolutionary processes can regularly generate events that appear hig~ly unlikely when compared to the universe of all possIble events. Models incorporating this evolutionary dynamic we call "constructionist" and we contrast them with traditional models which focus on static, equilibrium aspects. In popUlation genetics, construc~ionist models have provided a different perspective on several long-standing problems. We review three examples of the results from our own work. These results are: (1) simple evolutionary processes can result in multiple-allele polymorphisms maintained by selection that are highly unlikely to occur if fitnesses are chosen simultaneously and at random; (2) the frequency at which viabilities (e.g., heter?-zygote advantage or recessive lethality) occur III mutations is likely to be very different from that observed in established polymorphisms; and (3) the power of the Ewens-Watterson test of neutrality is low. Several extensions of the models are discussed, together with the sorts of questions they may answer. We conclude that a complete understanding of the evolutionary forces responsible for molecular polymorphism requires consideration of its temporal development as well as examination of its current form. B93016

The Generation and Maintenance of Genetic Variation by Frequency-Dependent Selection: Constructing Polymorphisms Under the Pairwise Interaction Model

“…Somewhat counter to expectation, equilibrium distributions of alleles remain far less centered than expected by chance. Our results here mirror the findings of the constant-viability construction approach studies done in the 1990s (Spencer and Marks 1988, 1992, 1993Marks and Spencer 1991). They found that constantviability construction approaches produce allele-frequency distributions that are less central than expected by chance (Marks and Spencer 1991;Spencer and Marks 1992, Figure 1).…”

“…A more natural way to model mutation would be to assume each mutant allele to be descended from an existing parent allele (Spencer and Marks 1993), and such investigations are already underway. Further modeling projects will address the effects of variable mutation rate, as well as finite population size, drift, and spatial structure on the potential for polymorphism under FDS.…”

Effects of Genetic Drift and Gene Flow on the Selective Maintenance of Genetic Variation

“…The power of such explanations, however, has been augmented by the realization that selectively maintained polymorphisms may build up over time, accumulating rare beneficial mutations (Spencer and Marks 1993). By bombarding populations under selection with a steady stream of novel mutations, using what we here call a construction approach, the parameter space that allows selectively maintained polymorphisms can be more easily reached (Spencer and Marks 1988).…”

An Asymmetric Model of Heterozygote Advantage at Major Histocompatibility Complex Genes: Degenerate Pathogen Recognition and Intersection Advantage

“…This nonequilibrium, ''constructionist'' approach (following Spencer and Marks 1993) has proved very useful in the analysis of polymorphism maintenance in the past (Spencer and Marks 1988Marks and Spencer 1991). Researchers utilizing this constructionist approach have shown that polymorphism is far more easily generated and maintained via a simple process of allele introduction and selection than equilibrium-based approaches would suggest (Spencer and Marks 1993). Therefore, simulations were initiated with a single allele and new alleles were introduced at one of two per-locus rates (m L ¼ 2m, where m is the per-gene mutation rate): 10 À5 and 10 À6 .…”