The extended evolutionary synthesis invokes a role for development in shaping adaptive evolution, which in population genetics terms corresponds to mutation-biased adaptation. Critics have claimed that clonal interference makes mutation-biased adaptation rare. We consider the behaviour of two simultaneously adapting traits, one with larger mutation rate U , the other with larger selection coefficient s , using asexual travelling wave models. We find that adaptation is dominated by whichever trait has the faster rate of adaptation v in isolation, with the other trait subject to evolutionary stalling. Reviewing empirical claims for mutation-biased adaptation, we find that not all occur in the ‘origin-fixation’ regime of population genetics where v is only twice as sensitive to s as to U . In some cases, differences in U are at least ten to twelve times larger than differences in s , as needed to cause mutation-biased adaptation even in the ‘multiple mutations’ regime. Surprisingly, when U > s in the ‘diffusive-mutation’ regime, the required sensitivity ratio is also only two, despite pervasive clonal interference. Given two traits with identical v , the benefit of having higher s is surprisingly small, occurring largely when one trait is at the boundary between the origin-fixation and multiple mutations regimes.

The Extended Evolutionary Synthesis invokes a role for development in shaping adaptive evolution, which in population genetics terms corresponds to mutationbiased adaptation. Critics have claimed that clonal in-5 terference makes mutation-biased adaptation rare. We consider the behavior of two simultaneously adapting traits, one with larger mutation rate U , the other with larger selection coefficient s, using asexual traveling wave models. We find that adaptation is dominated 10

Genetic covariances represent a combination of pleiotropy and linkage disequilibrium, shaped by the population's history. Observed genetic covariance is most often interpreted in pleiotropic terms. In particular, functional constraints restricting which phenotypes are physically possible can lead to a stable G matrix with high genetic variance in fitness-associated traits, and high pleiotropic negative covariance along the phenotypic curve of constraint. In contrast, population genetic models of relative fitness assume endless adaptation without constraint, through a series of selective sweeps that are well described by recent traveling wave models. We describe the implications of such population genetic models for the G matrix when pleiotropy is excluded by design, such that all covariance comes from linkage disequilibrium. The G matrix is far less stable than has previously been found, fluctuating over the timescale of selective sweeps. However, its orientation is relatively stable, corresponding to high genetic variance in fitnessassociated traits and strong negative covariance-the same pattern often interpreted in terms of pleiotropic constraints but caused instead by linkage disequilibrium. We find that different mechanisms drive the instabilities along vs. perpendicular to the fitness gradient. The origin of linkage disequilibrium is not drift, but small amounts of linkage disequilibrium are instead introduced by mutation and then amplified during competing selective sweeps. This illustrates the need to integrate a broader range of population genetic phenomena into quantitative genetics.