Effects of recombination on the evolvability, genetic diversity and mutational robustness of neutrally evolving populations

Many effects attributed to recombination have been invoked to explain the advantage of sex. The most prominent arguments focus on either evolvability, genetic diversity, or mutational robustness to justify why the benefit of recombination overcomes its costs, with partially contradicting results. As a consequence, understanding which aspects of recombination are most important in a given situation remains an open problem for theoretical and experimental research. In this study, we focus on finite populations evolving on neutral networks, which already display remarkably complex behavior. We aim to provide a comprehensive overview of the effects of recombination by jointly considering different measures of evolvability, genetic diversity, and mutational robustness over a broad parameter range, such that many evolutionary regimes are covered. We find that several of these measures vary non-monotonically with the rates of mutation and recombination. Moreover, the presence of lethal genotypes that introduce inhomogeneities in the network of viable states qualitatively alters the effects of recombination. We conclude that conflicting trends induced by recombination can be explained by an emerging trade-off between evolvability and genetic diversity on the one hand, and mutational robustness and fitness on the other. Finally, we discuss how different implementations of the recombination scheme in theoretical models can affect the observed dependence on recombination rate through a coupling between recombination and genetic drift.

Mutational robustness changes during long-term adaptation in laboratory budding yeast populations

As an adapting population traverses the fitness landscape, its local neighborhood (i.e., the collection of fitness effects of single-step mutations) can change shape because of interactions with mutations acquired during evolution. These changes to the distribution of fitness effects can affect both the rate of adaptation and the accumulation of deleterious mutations. However, while numerous models of fitness landscapes have been proposed in the literature, empirical data on how this distribution changes during evolution remains limited. In this study, we directly measure how the fitness landscape neighborhood changes during laboratory adaptation. Using a barcode-based mutagenesis system, we measure the fitness effects of 91 specific gene disruption mutations in genetic backgrounds spanning 8,000-10,000 generations of evolution in two constant environments. We find that the mean of the distribution of fitness effects decreases in one environment, indicating a reduction in mutational robustness, but does not change in the other. We show that these distribution-level patterns result from biases in variable patterns of epistasis at the level of individual mutations, including fitness-correlated and idiosyncratic epistasis.

Polerovirus Genomic Variation

The polerovirus (family Solemoviridae, genus Polerovirus) genome consists of single, positive strand RNA organized in overlapping open reading frames (ORFs) that, in addition to others, code for protein 0 (P0, a gene silencing suppressor), a coat protein (CP, ORF3) and a read-through domain (ORF5) that is fused to the CP to form a CP-RT protein. The genus Polerovirus contains 26 virus species that infect a wide variety of plants from cereals to cucurbits, to peppers. Poleroviruses are transmitted by a wide range of aphid species in the genera Rhopalosiphum, Stiobion, Aphis, and Myzus. Aphid transmission is mediated both by the CP and the CP-RT. In viruses, mutational robustness and structural flexibility are necessary for maintaining functionality in genetically diverse sets of host plants and vectors. Under this scenario, within a virus genome, mutations preferentially accumulate in areas that are determinants of host adaptation or vector transmission. In this study, we profiled genomic variation in poleroviruses. Consistent with their multifunctional nature, single nucleotide variation and selection analyses showed that ORFs coding for P0 and the read-through domain within the CP-RT are the most variable and contain the highest frequency of sites under positive selection. An order/disorder analysis showed that protein P0 is not disordered. In contrast, proteins CP-RT and VPg contain areas of disorder. Disorder is a property of multifunctional proteins with multiple interaction partners. Results described here suggest that using contrasting mechanisms, P0, VPg and CP-RT mediate adaptation to host plants, to vectors, and are contributors to the broad host and vector range of poleroviruses. Profiling genetic variation across the polerovirus genome has practical applications in diagnostics, breeding for resistance, identification of susceptibility genes, and contributes to our understanding of virus interactions with their host, vectors, and environment.

Promoter sequence and architecture determine expression variability and confer robustness to genetic variants

Genetic and environmental exposures cause variability in gene expression. Although most genes are affected in a population, their effect sizes vary greatly, indicating the existence of regulatory mechanisms that could amplify or attenuate expression variability. Here, we investigate the relationship between the sequence and transcription start site architectures of promoters and their expression variability across human individuals. We find that expression variability is largely determined by a promoter's DNA sequence and its binding sites for specific transcription factors. We further demonstrate that flexible usage of transcription start sites within a promoter attenuates variability, providing transcriptional and mutational robustness.

A Mathematical Analysis of HDV Genotypes: From Molecules to Cells

Hepatitis D virus (HDV) is classified according to eight genotypes. The various genotypes are included in the HDVdb database, where each HDV sequence is specified by its genotype. In this contribution, a mathematical analysis is performed on RNA sequences in HDVdb. The RNA folding predicted structures of the Genbank HDV genome sequences in HDVdb are classified according to their coarse-grain tree-graph representation. The analysis allows discarding in a simple and efficient way the vast majority of the sequences that exhibit a rod-like structure, which is important for the virus replication, to attempt to discover other biological functions by structure consideration. After the filtering, there remain only a small number of sequences that can be checked for their additional stem-loops besides the main one that is known to be responsible for virus replication. It is found that a few sequences contain an additional stem-loop that is responsible for RNA editing or other possible functions. These few sequences are grouped into two main classes, one that is well-known experimentally belonging to genotype 3 for patients from South America associated with RNA editing, and the other that is not known at present belonging to genotype 7 for patients from Cameroon. The possibility that another function besides virus replication reminiscent of the editing mechanism in HDV genotype 3 exists in HDV genotype 7 has not been explored before and is predicted by eigenvalue analysis. Finally, when comparing native and shuffled sequences, it is shown that HDV sequences belonging to all genotypes are accentuated in their mutational robustness and thermodynamic stability as compared to other viruses that were subjected to such an analysis.

The Mutational Robustness of the Genetic Code and Codon Usage in Environmental Context: A Non-Extremophilic Preference?

The genetic code was evolved, to some extent, to minimize the effects of mutations. The effects of mutations depend on the amino acid repertoire, the structure of the genetic code and frequencies of amino acids in proteomes. The amino acid compositions of proteins and corresponding codon usages are still under selection, which allows us to ask what kind of environment the standard genetic code is adapted to. Using simple computational models and comprehensive datasets comprising genomic and environmental data from all three domains of Life, we estimate the expected severity of non-synonymous genomic mutations in proteins, measured by the change in amino acid physicochemical properties. We show that the fidelity in these physicochemical properties is expected to deteriorate with extremophilic codon usages, especially in thermophiles. These findings suggest that the genetic code performs better under non-extremophilic conditions, which not only explains the low substitution rates encountered in halophiles and thermophiles but the revealed relationship between the genetic code and habitat allows us to ponder on earlier phases in the history of Life.

Symmetry and simplicity spontaneously emerge from the algorithmic nature of evolution

Engineers routinely design systems to be modular and symmetric in order to increase robustness to perturbations and to facilitate alterations at a later date. Biological structures also frequently exhibit modularity and symmetry, but the origin of such trends is much less well understood. It can be tempting to assume -- by analogy to engineering design -- that symmetry and modularity arise from natural selection. But evolution, unlike engineers, cannot plan ahead, and so these traits must also afford some immediate selective advantage which is hard to reconcile with the breadth of systems where symmetry is observed. Here we introduce an alternative non-adaptive hypothesis based on an algorithmic picture of evolution. It suggests that symmetric structures preferentially arise not just due to natural selection, but also because they require less specific information to encode, and are therefore much more likely to appear as phenotypic variation through random mutations. Arguments from algorithmic information theory can formalise this intuition, leading to the prediction that many genotype-phenotype maps are exponentially biased towards phenotypes with low descriptional complexity. A preference for symmetry is a special case of this bias towards compressible descriptions. We test these predictions with extensive biological data, showing that that protein complexes, RNA secondary structures, and a model gene-regulatory network all exhibit the expected exponential bias towards simpler (and more symmetric) phenotypes. Lower descriptional complexity also correlates with higher mutational robustness, which may aid the evolution of complex modular assemblies of multiple components.

Phylogenetic analysis of mutational robustness based on codon usage supports that the standard genetic code does not prefer extreme environments

The mutational robustness of the genetic code is rarely discussed in the context of biological diversity, such as codon usage and related factors, often considered as independent of the actual organism’s proteome. Here we put the living beings back to picture and use distortion as a metric of mutational robustness. Distortion estimates the expected severities of non-synonymous mutations measuring it by amino acid physicochemical properties and weighting for codon usage. Using the biological variance of codon frequencies, we interpret the mutational robustness of the standard genetic code with regards to their corresponding environments and genomic compositions (GC-content). Employing phylogenetic analyses, we show that coding fidelity in physicochemical properties can deteriorate with codon usages adapted to extreme environments and these putative effects are not the artefacts of phylogenetic bias. High temperature environments select for codon usages with decreased mutational robustness of hydrophobic, volumetric, and isoelectric properties. Selection at high saline concentrations also leads to reduced fidelity in polar and isoelectric patterns. These show that the genetic code performs best with mesophilic codon usages, strengthening the view that LUCA or its ancestors preferred lower temperature environments. Taxonomic implications, such as rooting the tree of life, are also discussed.