“…This blunt force approach, however, frequently identifies only the most severe mutations, dominated by those which completely abrogate or grossly impair gene function (Albertson, et al, 2009). This is in stark contrast to the typical trajectory of novel mutations in natural populations where natural selection and genetic drift lead to an accumulation of mutations with small to moderate effects (Rockman, 2012;Noble, et al, 2017;Teotónio, et al, 2017). Models utilizing natural variation in genetic pathways can reveal physiological mechanisms that modify pathogen interactions and disease which would likely be missed using a mutagenesis approach and evolution itself can be used to select for alleles conferring a desired phenotype (Kammenga, et al, 2008;Teotónio et al, 2017;Gao, et al, 2018;Hahnel, et al, 2018).…”