The Power of Natural Variation for Model Organism Biology

Genetic background effects have long been recognized and, in some cases studied, but they are often viewed as a nuisance by molecular biologists. We suggest that genetic variation currently represents a critical frontier for molecular studies. Human genetics has seen a surge of interest in genetic variation and its contributions to disease, but insights into disease mechanisms are difficult since information about gene function is lacking. By contrast, model organism genetics has excelled at revealing molecular mechanisms of cellular processes, but often de-emphasizes genetic variation and its functional consequences. We argue that model organism biology would benefit from incorporating natural variation, both to capture how well laboratory lines exemplify the species they represent and to inform on molecular processes and their variability. Such a synthesis would also greatly expand the relevance of model systems for studies of complex trait variation, including disease.

TrendsLaboratory lines of model organisms have provided a wealth of information about biological functions. Many of these lines are derived from species with significant genetic and functional variation in nature.The longstanding focus on particular genetic backgrounds has enabled the elucidation of core biological functions, but has limited our understanding of the levels and impacts of natural variation found in wild populations.A broader synthesis incorporating natural variation into model organism research would illuminate biological mechanisms, reveal the genetic basis for phenotypic variation, and solidify the importance of model organisms for understanding both basic and personalized genetics.