Changing preferences: deformation of single position amino acid fitness landscapes and evolution of proteins

Abstract

The fitness landscape-the function that relates genotypes to fitness-and its role in directing evolution are a central object of evolutionary biology. However, its huge dimensionality precludes understanding of even the basic aspects of its shape. One way to approach it is to ask a simpler question: what are the properties of a function that assigns fitness to each possible variant at just one particular site-a single position fitness landscape-and how does it change in the course of evolution? Analyses of genomic data from multiple species and multiple individuals within a species have proved beyond reasonable doubt that fitness functions of positions throughout the genome do themselves change with time, thus shaping protein evolution. Here, I will briefly review the literature that addresses these dynamics, focusing on recent genome-scale analyses of fitness functions of amino acid sites, i.e. vectors of fitnesses of 20 individual amino acid variants at a given position of a protein. The set of amino acids that confer high fitness at a particular position changes with time, and the rate of this change is comparable with the rate at which a position evolves, implying that this process plays a major role in evolutionary dynamics. However, the causes of these changes remain largely unclear.

Keywords: epistasis; macroevolution; microevolution; proteins; selection.

Figure 1.

Single position fitness landscape (SPFL). Horizontal rows correspond to individual amino acids at a site. (a) At each moment of time, a protein can be described by the fitness values of all its one-step mutational neighbours (for simplicity, all amino acid variants are assumed to be accessible by mutation). The currently predominant amino acid at each site (surrounded by black rectangles) confers high fitness. (b) The SPFL of position 7. (c) The change of the SPFL with time; the fitness of individual amino acids at the position may increase, decrease or remain invariant owing to changes in the genomic background or of the environment. Fitness changes are modelled as a Poisson process, as in [7].

Figure 2.

Inferring changes in the SPFL. Left column, constant SPFL; right column, varying SPFL. (a) Abundance of positive selection and sustained sequence divergence. (b) Different sets of permitted variants at different time points (or in different species). (c) Reduction in the rate of reversals with time, owing to the ancestral variant being no longer fit. (d) Positive selection provoked by a change elsewhere in the genome (triangle). (e) Direct data on low (cross) or high (check mark) fitness of the ancestral variant. Broken lines, neutral substitutions; solid lines, positively selected substitutions. The currently predominant amino acid at each site is surrounded by a black rectangle.