Common, consequential, and actively maintained: a neo-balance view of genetic variation

Mark Christopher Bitter , Paul Schmidt, Dmitri Petrov

A fundamental and still unfinished task of evolutionary biology is to understand the nature of genetic variation and the evolutionary forces that shape it. The traditional approach to this problem is through retrospective inference from patterns in contemporary, static DNA sequence data. The prevailing view that emerged from these studies and from theoretical research is that segregating genetic polymorphism is either deleterious or effectively neutral and thus governed primarily by purifying natural selection and stochastic forces such as genetic drift or draft. In this Perspective, we review emerging evidence that challenges this paradigm. In particular, evolution-in-action studies that directly measure selection at individual loci throughout the evolutionary process have revealed hundreds to thousands of loci with common polymorphism exhibiting strong fitness effects and suggest that these polymorphisms must be maintained through some form of balancing selection. These data call for a new framework for understanding population genetic variation, which we term neo-balance. We discuss the theoretical and practical implications of this new paradigm and outline an empirical agenda to incorporate these observations into the study of biological variation and evolution.