Evolution of complex adaptations in molecular systems

Abstract

A central challenge in evolutionary biology concerns the mechanisms by which complex adaptations arise. Such adaptations depend on the fixation of multiple, highly specific mutations, where intermediate stages of evolution seemingly provide little or no benefit. It is generally assumed that the establishment of complex adaptations is very slow in nature, as evolution of such traits demands special population genetic or environmental circumstances. However, blueprints of complex adaptations in molecular systems are pervasive, indicating that they can readily evolve. We discuss the prospects and limitations of non-adaptive scenarios, which assume multiple neutral or deleterious steps in the evolution of complex adaptations. Next, we examine how complex adaptations can evolve by natural selection in changing environment. Finally, we argue that molecular 'springboards', such as phenotypic heterogeneity and promiscuous interactions facilitate this process by providing access to new adaptive paths.

Figure 1. Concept of complex adaptations

Two mutations (a → A and b → B) have to occur simultaneously to provide a fitness advantage. Note that the individual mutations depicted here are neutral, but they could also be deleterious.

Figure 2. Main classes and examples of complex adaptations in molecular systems

Establishment of a new disulfide bond (S-S) from two adjacent sulfhydryl groups (-SH) within the same protein molecule represents an example of intramolecular complex adaptation. The origin of new transcription factor – DNA binding site interactions, multi-step metabolic pathways and multi-subunit complexes all qualify as intermolecular complex adaptations requiring specific mutations in multiple genes.

Figure 3. Evolutionary mechanisms of establishing complex adaptations

A) Non-adaptive origin of complex adaptations can occur through sequential fixation of mutations in small populations where the intermediate mutation first goes to fixation through genetic drift (upper plot). Alternatively, in large populations a beneficial second mutation can arise in a descendant of the intermediate mutation and they fix simultaneously without the population ever going through a pure intermediate state (lower plot). Allele frequency plots depict the dynamics of the neutral intermediate mutation and the beneficial second mutation. B) Simplified metabolic network scheme in which enzyme functions A and B are asymmetrically dependent on each other as a consequence of preadaptation. In the first evolutionary stage, the network can metabolize substrate 1 and this serves as a preadaptation to utilize substrate 2 via the acquisition of enzyme A. Because in the second stage both enzymes A and C produce the same intermediate metabolite, the activity of downstream enzyme B does not exclusively depend on A. In contrast, A can only be active under steady state conditions when B is active, hence their functional dependence is asymmetric. C) Evolution of complex adaptations via adaptive by-passes in extra genotype dimensions. The figure depicts a simplified scenario where evolution from a low-fitness genotype (ab) to a high-fitness one (AB) involves neutral intermediary steps, but a mutation at a third locus (c → C) opens new uphill trajectories where all intermediate steps are beneficial. Fitness of genotypes is represented by a color scale. D) Evolution in alternating environments promotes escape from local fitness optima through series of purely adaptive walks. The horizontal plane represents genotype space, the vertical axis represents fitness, and arrows indicate uphill evolutionary trajectories. Environmental change alters the fitness landscape in such a way that a fitness valley in the target environment becomes a fitness peak in the intermediate environment hence facilitating valley crossing.

Figure 4. Molecular springboards of complex adaptations

Molecular mechanisms that potentiate the establishment of complex adaptations by eliminating fitness valleys (A) or opening up more direct mutational paths (B-C). A) Permissive mutations that increase protein stability allow the fixation of function-altering mutations that would otherwise inactivate the protein. Note that the stability-enhancing mutation might not have any fitness effect. B) The presence of low-level enzyme side activities facilitates the adaptive evolution of multi-step metabolic pathways. A two-step pathway with metabolites A-C is depicted where the second metabolic step can be weakly catalyzed by the promiscuous side activity of enzyme E₂ (stage 1). Note that E₂ has a primary enzymatic activity outside of the pathway of interest. Gain of an enzyme (E₁) catalyzing the first reaction immediately confers a fitness advantage as it allows the operation of the pathway, albeit with low activity (stage 2). A second mutation enhances the side activity of E₂ and thereby results in a fully functional pathway (stage 3). C) Phenotypic mutations allow selection for intermediate mutations that would otherwise be neutral. The figure depicts a situation where two mutations are required for a novel protein function. Owing to transcriptional and translational errors, a small fraction of the proteome already possesses one of the mutations in a non-heritable form (stage 1). A genotype carrying the other mutation thus has a selective advantage as some of its proteins will carry out the new function (stage 2). A later adaptive genetic mutation provides the full fitness benefit by converting all protein molecules within the cell from the ancestral into the new function (stage 3). Mutations / errors are depicted by white dots.