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Simple genotype-to-phenotype maps allow for easy prediction about
selective pressure and evolution at the level of genotype. For most traits,
the genotype-to-phenotype map is non-trivial, making straightforward
predictions challenging. In this talk, we examine evolutionary dynamics
with a non-trivial and mathematically tractable genotype-to-phenotype map:
metabolism. Using evolutionary simulation and theory, we find that
selection at the level of genes may be non-identifiable and at best paints
an incoherent picture, whereas as selection on a preferred direction in
phenotype space, the collective mode, appears to be a natural object of
selection. We develop and analyze a theory of collective modes and help
clarify the relative roles of genotype and phenotype in evolution, as well
as providing an explanation for variability in polygenic traits.