Kavita Jain

Purifying Selection, Drift, and Reversible Mutation with Arbitrarily High Mutation Rates

2014-01-01T00:00:00Z

Purifying Selection, Drift, and Reversible Mutation with Arbitrarily High Mutation Rates Charlesworth, Brian; Jain, Kavita Some species exhibit very high levels of DNA sequence variability; there is also evidence for the existence of heritable epigenetic variants that experience state changes at a much higher rate than sequence variants. In both cases, the resulting high diversity levels within a population (hyperdiversity) mean that standard population genetics methods are not trustworthy. We analyze a population genetics model that incorporates purifying selection, reversible mutations, and genetic drift, assuming a stationary population size. We derive analytical results for both population parameters and sample statistics and discuss their implications for studies of natural genetic and epigenetic variation. In particular, we find that (1) many more intermediate-frequency variants are expected than under standard models, even with moderately strong purifying selection, and (2) rates of evolution under purifying selection may be close to, or even exceed, neutral rates. These findings are related to empirical studies of sequence and epigenetic variation. Restricted Access

Two-point correlation function of an exclusion process with hole-dependent rates

2014-01-01T00:00:00Z

Two-point correlation function of an exclusion process with hole-dependent rates Priyanka; Ayyer, Arvind; Jain, Kavita We consider an exclusion process on a ring in which a particle hops to an empty neighboring site with a rate that depends on the number of vacancies n in front of it. In the steady state, using the well-known mapping of this model to the zero-range process, we write down an exact formula for the partition function and the particle-particle correlation function in the canonical ensemble. In the thermodynamic limit, we find a simple analytical expression for the generating function of the correlation function. This result is applied to the hop rate u(n) = 1 + (b/n) for which a phase transition between high-density laminar phase and low-density jammed phase occurs for b > 2. For these rates, we find that at the critical density, the correlation function decays algebraically with a continuously varying exponent b - 2. We also calculate the two-point correlation function above the critical density and find that the correlation length diverges with a critical exponent nu = 1/(b - 2) for b < 3 and 1 for b > 3. These results are compared with those obtained using an exact series expansion for finite systems. Restricted Access

Adaptive walks and distribution of beneficial fitness effects

2014-01-01T00:00:00Z

Adaptive walks and distribution of beneficial fitness effects Seetharaman, Sarada; Jain, Kavita We study the adaptation dynamics of a maladapted asexual population on rugged fitness landscapes with many local fitness peaks. The distribution of beneficial fitness effects is assumed to belong to one of the three extreme value domains, viz. Weibull, Gumbel, and Frechet. We work in the strong selection-weak mutation regime in which beneficial mutations fix sequentially, and the population performs an uphill walk on the fitness landscape until a local fitness peak is reached. A striking prediction of our analysis is that the fitness difference between successive steps follows a pattern of diminishing returns in the Weibull domain and accelerating returns in the Frechet domain, as the initial fitness of the population is increased. These trends are found to be robust with respect to fitness correlations. We believe that this result can be exploited in experiments to determine the extreme value domain of the distribution of beneficial fitness effects. Our work here differs significantly from the previous ones that assume the selection coefficient to be small. On taking large effect mutations into account, we find that the length of the walk shows different qualitative trends from those derived using small selection coefficient approximation. Restricted Access

Length of adaptive walk on uncorrelated and correlated fitness landscapes

2014-01-01T00:00:00Z

Length of adaptive walk on uncorrelated and correlated fitness landscapes Seetharaman, Sarada; Jain, Kavita We consider the adaptation dynamics of an asexual population that walks uphill on a rugged fitness landscape which is endowed with a large number of local fitness peaks. We work in a parameter regime where only those mutants that are a single mutation away are accessible, as a result of which the population eventually gets trapped at a local fitness maximum and the adaptive walk terminates. We study how the number of adaptive steps taken by the population before reaching a local fitness peak depends on the initial fitness of the population, the extreme value distribution of the beneficial mutations, and correlations among the fitnesses. Assuming that the relative fitness difference between successive steps is small, we analytically calculate the average walk length for both uncorrelated and correlated fitnesses in all extreme value domains for a given initial fitness. We present numerical results for the model where the fitness differences can be large and find that the walk length behavior differs from that in the former model in the Frechet domain of extreme value theory. We also discuss the relevance of our results to microbial experiments. Restricted Access