Predictability of evolutionary trajectories in fitness landscapes

Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness landscape. We report an exhaustive analysis of fitness landscapes constructed with an off-lattice model of protein folding where fitness is equated with robustness to misfolding. This model mimics the essential features of the interactions between amino acids, is consistent with the key paradigms of protein folding and reproduces the universal distribution of evolutionary rates among orthologous proteins. We introduce mean path divergence as a quantitative measure of the degree to which the starting and ending points determine the path of evolution in fitness landscapes. Global measures of landscape roughness are good predictors of path divergence in all studied landscapes: the mean path divergence is greater in smooth landscapes than in rough ones. The model-derived and experimental landscapes are significantly smoother than random landscapes and resemble additive landscapes perturbed with moderate amounts of noise; thus, these landscapes are substantially robust to mutation. The model landscapes show a deficit of suboptimal peaks even compared with noisy additive landscapes with similar overall roughness. We suggest that smoothness and the substantial deficit of peaks in the fitness landscapes of protein evolution are fundamental consequences of the physics of protein folding.Comment: 14 pages, 7 figure

Transmission Selects for HIV-1 Strains of Intermediate Virulence: A Modelling Approach

Recent data shows that HIV-1 is characterised by variation in viral virulence factors that is heritable between infections, which suggests that viral virulence can be naturally selected at the population level. A trade-off between transmissibility and duration of infection appears to favour viruses of intermediate virulence. We developed a mathematical model to simulate the dynamics of putative viral genotypes that differ in their virulence. As a proxy for virulence, we use set-point viral load (SPVL), which is the steady density of viral particles in blood during asymptomatic infection. Mutation, the dependency of survival and transmissibility on SPVL, and host effects were incorporated into the model. The model was fitted to data to estimate unknown parameters, and was found to fit existing data well. The maximum likelihood estimates of the parameters produced a model in which SPVL converged from any initial conditions to observed values within 100–150 years of first emergence of HIV-1. We estimated the 1) host effect and 2) the extent to which the viral virulence genotype mutates from one infection to the next, and found a trade-off between these two parameters in explaining the variation in SPVL. The model confirms that evolution of virulence towards intermediate levels is sufficiently rapid for it to have happened in the early stages of the HIV epidemic, and confirms that existing viral loads are nearly optimal given the assumed constraints on evolution. The model provides a useful framework under which to examine the future evolution of HIV-1 virulence

Seed Priming of Trifolium repens L. Improved Germination and Early Seedling Growth on Heavy Metal-Contaminated Soil

Abstract Seed priming effects on Trifolium repens were analysed both in Petri dishes and in two soils (one unpolluted soil and a soil polluted with Cd and Zn). Priming treatments were performed with gibberellic acid 0.1 mM at 22 °C during 12 h or with polyethylene glycol (−6.7 MPa) at 10 °C during 72 h. Both priming treatments increased the germination speed and the final germination percentages in the presence of 100 μM CdCl2 or 1 mM ZnSO4. Flow cytometry analysis demonstrated that the positive effect of priming was not related with any advancement of the cell cycle in embryos. Seed imbibition occurred faster for primed seeds than for control seeds. X-ray and electronic microscopy analysis suggested that circular depressions on the seed coat, in addition to tissue detachments inside the seed, could be linked to the higher rate of imbibition. Priming treatments had no significant impact on the behaviour of seedlings cultivated on nonpolluted soil while they improved seedling emergence and growth on polluted soil. The two priming treatments reduced Zn accumulation. Priming with gibberellic acid increased Cd accumulation by young seedlings while priming with polyethylene glycol reduced it. Priming improved the light phase of photosynthesis and strengthened the antioxidant system of stressed seedlings. Optimal priming treatment may thus be recommended as efficient tools to facilitate revegetation of former mining area