Elucidating the underlying rules that govern the phenotypic diversity observed in natural populations is an old but still unaccomplished goal in biology. In 1865, Gregor Mendel paved the way for the dissection of the underlying genetic basis of traits by setting out to understand the principles of heredity. To date, we still lack a global overview of the spectrum and continuum existing between Mendelian and complex traits within any natural population. In this respect, we recently performed a species-wide survey of Mendelian traits across a large population of isolates using the yeast Saccharomyces cerevisiae. By analyzing the distribution and the inheritance patterns of the trait, we have clearly shown that monogenic mutations can display a significant, variable, and continuous expressivity across different genetic backgrounds. Our study also demonstrated that combining the elegancy of both classical genetics and high-throughput genomics is more than valuable to dissect the genotype-phenotype relationship in natural populations.

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