Abstract
Most of our knowledge of dominance stems from studies of deleterious mutations. From these studies we know that most deleterious mutations are recessive, and that this recessivity arises from a hyperbolic relationship between protein function (i.e., protein concentration or activity) and fitness. Here we investigate whether this knowledge can be used to make predictions about the dominance of beneficial and deleterious mutations in a single gene. We employed a model system – the bacteriophage φ6 – that allowed us to generate a collection of mutations in haploid conditions so that it was not biased toward either dominant beneficial or recessive deleterious mutations. Screening for the ability to infect a bacterial host that does not permit infection by the wildtype φ6, we generated a collection of mutations in P3, a gene involved in attachment to the host and in phage particle assembly. The resulting collection contained mutations with both deleterious and beneficial effects on fitness. The deleterious mutations in our collection had additive effects on fitness and the beneficial mutations were recessive. Neither of these observations were predicted from previous studies of dominance. This pattern is not consistent with the hyperbolic (diminishing returns) relationship between protein function and fitness that is characteristic of enzymatic genes, but could have resulted from a curve of increasing returns.
Highlights
150 years after Mendel first observed recessive traits in pea plants [1], empirical studies have shown that most deleterious mutations are recessive [2,3,4]
We capitalized on the observation that in the bacteriophage w6, a phenotypic screen for mutations that expand host range yields a large collection of different mutations, mostly in the host attachment gene P3 [15,19]
Coinfecting Hosts We examined whether mutations were complemented during coinfections by comparing the effects of mutations when hosts were coinfected by two mutant bacteriophage and when hosts were coinfected by a wildtype and a mutant phage (Aa)
Summary
150 years after Mendel first observed recessive traits in pea plants [1], empirical studies have shown that most deleterious mutations are recessive [2,3,4]. For mutations in enzymatic genes, the dominance of the wildtype over most deleterious mutations results, from the hyperbolic relationship between enzyme concentration and flux through a metabolic pathway (see Figure 1). Empirical investigations of mutational effects in enzymes have confirmed that enzyme concentration is hyperbolically related to flux [5], and to fitness [7]. In cases like Huntington’s disease, where deleterious mutations are dominant, they typically occur in non-enzymatic genes (reviewed in [4])
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