The Boggarts of Biology: How Non-Genetic Changes Influence the Genotype

The notion that there is a one to one mapping from genotype to phenotype was overturned a long time ago. It is now well established that besides the genetic background, environmental inputs guide the development of phenotype. In addition, altered RNA and protein molecules also influence phenotype in conjunction with the external environment, leading to ‘non-genetic’ changes. The phenotypic variation we see across all living organisms therefore results from a combination of genetic and non-genetic changes. In spite of the prevalent idea that variability arising from non-genetic changes is transient and does not influence evolution, recent work has shown that it can impact both short and long-term adaptation. In this review, I propose that one way in which non-genetic inputs can affect evolution is by indirectly influencing genetic change. I classify and review the many ways in which non-genetic changes influence genotype and impact cellular fitness across generations, with an emphasis on the enticing idea that non-genetic changes act as stepping stones for genetic adaptation. Overall, I review how non-genetic changes impact phenotype via their influence on the genotype, and thus can play a role in evolutionary change.