Mutational robustness and the role of buffer genes in evolvability.

Organisms rely on mutations to fuel adaptive evolution. However, many mutations impose a negative effect on fitness. Cells may have therefore evolved mechanisms that affect the phenotypic effects of mutations, thus conferring mutational robustness. Specifically, so-called buffer genes are hypothesized to interact directly or indirectly with genetic variation and reduce its effect on fitness. Environmental or genetic perturbations can change the interaction between buffer genes and genetic variation, thereby unmasking the genetic variation's phenotypic effects and thus providing a source of variation for natural selection to act on. This review provides an overview of our understanding of mutational robustness and buffer genes, with the chaperone gene HSP90 as a key example. It discusses whether buffer genes merely affect standing variation or also interact with de novo mutations, how mutational robustness could influence evolution, and whether mutational robustness might be an evolved trait or rather a mere side-effect of complex genetic interactions.

Molecular determinants of protein evolvability.

The plethora of biological functions that sustain life is rooted in the remarkable evolvability of proteins. An emerging view highlights the importance of a protein's initial state in dictating evolutionary success. A deeper comprehension of the mechanisms that govern the evolvability of these initial states can provide invaluable insights into protein evolution. In this review, we describe several molecular determinants of protein evolvability, unveiled by experimental evolution and ancestral sequence reconstruction studies. We further discuss how genetic variation and epistasis can promote or constrain functional innovation and suggest putative underlying mechanisms. By establishing a clear framework for these determinants, we provide potential indicators enabling the forecast of suitable evolutionary starting points and delineate molecular mechanisms in need of deeper exploration.

Evolving a favorable distribution for mutation effects.

Tandem-repeat DNA sequences appear to be singularly capable of yielding abundant repeat-number mutations with a potentially advantageous distribution of fitness effects. Although knowing the rates and relative proportions of deleterious, neutral and beneficial mutations is fundamental for understanding evolvability, analysis of adaptation routinely overlooks small-effect mutations arising in tandem repeats.

Disentangling variational bias: the roles of development, mutation, and selection.

The extraordinary diversity and adaptive fit of organisms to their environment depends fundamentally on the availability of variation. While most population genetic frameworks assume that random mutations produce isotropic phenotypic variation, the distribution of variation available to natural selection is more restricted, as the distribution of phenotypic variation is affected by a range of factors in developmental systems. Here, we revisit the concept of developmental bias - the observation that the generation of phenotypic variation is biased due to the structure, character, composition, or dynamics of the developmental system - and argue that a more rigorous investigation into the role of developmental bias in the genotype-to-phenotype map will produce fundamental insights into evolutionary processes, with potentially important consequences on the relation between micro- and macro-evolution. We discuss the hierarchical relationships between different types of variational biases, including mutation bias and developmental bias, and their roles in shaping the realized phenotypic space. Furthermore, we highlight the challenges in studying variational bias and propose potential approaches to identify developmental bias using modern tools.

Utilizing developmental dynamics for evolutionary prediction and control.

Understanding, predicting, and controlling the phenotypic consequences of genetic and environmental change is essential to many areas of fundamental and applied biology. In evolutionary biology, the generative process of development is a major source of organismal evolvability that constrains or facilitates adaptive change by shaping the distribution of phenotypic variation that selection can act upon. While the complex interactions between genetic and environmental factors during development may appear to make it impossible to infer the consequences of perturbations, the persistent observation that many perturbations result in similar phenotypes indicates that there is a logic to what variation is generated. Here, we show that a general representation of development as a dynamical system can reveal this logic. We build a framework that allows predicting the phenotypic effects of perturbations, and conditions for when the effects of perturbations of different origins are concordant. We find that this concordance is explained by two generic features of development, namely the dynamical dependence of the phenotype on itself and the fact that all perturbations must affect the developmental process to have an effect on the phenotype. We apply our theoretical framework to classical models of development and show that it can be used to predict the evolutionary response to selection using information of plasticity and to accelerate evolution in a desired direction. The framework we introduce provides a way to quantitatively interchange perturbations, opening an avenue of perturbation design to control the generation of variation.

Evolvability and trait function predict phenotypic divergence of plant populations.

Understanding the causes and limits of population divergence in phenotypic traits is a fundamental aim of evolutionary biology, with the potential to yield predictions of adaptation to environmental change. Reciprocal transplant experiments and the evaluation of optimality models suggest that local adaptation is common but not universal, and some studies suggest that trait divergence is highly constrained by genetic variances and covariances of complex phenotypes. We analyze a large database of population divergence in plants and evaluate whether evolutionary divergence scales positively with standing genetic variation within populations (evolvability), as expected if genetic constraints are evolutionarily important. We further evaluate differences in divergence and evolvability-divergence relationships between reproductive and vegetative traits and between selfing, mixed-mating, and outcrossing species, as these factors are expected to influence both patterns of selection and evolutionary potentials. Evolutionary divergence scaled positively with evolvability. Furthermore, trait divergence was greater for vegetative traits than for floral (reproductive) traits, but largely independent of the mating system. Jointly, these factors explained ~40% of the variance in evolutionary divergence. The consistency of the evolvability-divergence relationships across diverse species suggests substantial predictability of trait divergence. The results are also consistent with genetic constraints playing a role in evolutionary divergence.

Developmental bias predicts 60 million years of wing shape evolution.

The degree to which developmental biases affect trait evolution is subject to much debate. Here, we first quantify fluctuating asymmetry as a measure of developmental variability, i.e., the propensity of developmental systems to create some phenotypic variants more often than others, and show that it predicts phenotypic and standing genetic variation as well as deep macroevolutionary divergence in wing shape in sepsid flies. Comparing our data to the findings of a previous study demonstrates that developmental variability in the sepsid fly Sepsis punctum strongly aligns with mutational, standing genetic, and macroevolutionary variation in the Drosophilidae--a group that diverged from the sepsid lineage ca. 64 My ago. We also find that developmental bias in S. punctum wing shape aligns with the effects of allometry, but less so with putatively adaptive thermal plasticity and population differentiation along latitude. Our findings demonstrate that developmental bias in fly wings predicts evolvability and macroevolutionary trajectories on a much greater scale than previously appreciated but also suggest that causal explanations for such alignments may go beyond simple constraint hypotheses.

Modeling the evolution of recombination plasticity: A prospective review.

Meiotic recombination is one of the main sources of genetic variation, a fundamental factor in the evolutionary adaptation of sexual eukaryotes. Yet, the role of variation in recombination rate and other recombination features remains underexplored. In this review, we focus on the sensitivity of recombination rates to different extrinsic and intrinsic factors. We briefly present the empirical evidence for recombination plasticity in response to environmental perturbations and/or poor genetic background and discuss theoretical models developed to explain how such plasticity could have evolved and how it can affect important population characteristics. We highlight a gap between the evidence, which comes mostly from experiments with diploids, and theory, which typically assumes haploid selection. Finally, we formulate open questions whose solving would help to outline conditions favoring recombination plasticity. This will contribute to answering the long-standing question of why sexual recombination exists despite its costs, since plastic recombination may be evolutionary advantageous even in selection regimes rejecting any non-zero constant recombination.

Genetic architecture of dispersal and local adaptation drives accelerating range expansions.

Contemporary evolution has the potential to significantly alter biotic responses to global change, including range expansion dynamics and biological invasions. Models predicting range dynamics often make highly simplifying assumptions about the genetic architecture underlying relevant traits. However, genetic architecture defines evolvability and higher-order evolutionary processes, which determine whether evolution will be able to keep up with environmental change or not. Therefore, we here study the impact of the genetic architecture of dispersal and local adaptation, two central traits of high relevance for range expansions, on the dynamics and predictability of invasion into an environmental gradient, such as temperature. In our theoretical model we assume that dispersal and local adaptation traits result from the products of two noninteracting gene-regulatory networks (GRNs). We compare our model to simpler quantitative genetics models and show that in the GRN model, range expansions are accelerating and less predictable. We further find that accelerating dynamics in the GRN model are primarily driven by an increase in the rate of local adaptation to novel habitats which results from greater sensitivity to mutation (decreased robustness) and increased gene expression. Our results highlight how processes at microscopic scales, here within genomes, can impact the predictions of large-scale, macroscopic phenomena, such as range expansions, by modulating the rate of evolution.

Mutation protocols share with sexual reproduction the physiological role of producing genetic variation within 'constraints that deconstrain'.

Because the universe of possible DNA sequences is inconceivably vast, organisms have evolved mechanisms for exploring DNA sequence space while substantially reducing the hazard that would otherwise accrue to any process of random, accidental mutation. One such mechanism is meiotic recombination. Although sexual reproduction imposes a seemingly paradoxical 50% cost to fitness, sex evidently prevails because this cost is outweighed by the advantage of equipping offspring with genetic variation to accommodate environmental vicissitudes. The potential adaptive utility of additional mechanisms for producing genetic variation has long been obscured by a presumption that the vast majority of mutations are deleterious. Perhaps surprisingly, the probability for adaptive variation can be increased by several mechanisms that generate mutations abundantly. Such mechanisms, here called 'mutation protocols', implement implicit 'constraints that deconstrain'. Like meiotic recombination, they produce genetic variation in forms that minimize potential for harm while providing a reasonably high probability for benefit. One example is replication slippage of simple sequence repeats (SSRs); this process yields abundant, reversible mutations, typically with small quantitative effect on phenotype. This enables SSRs to function as adjustable 'tuning knobs'. There exists a clear pathway for SSRs to be shaped through indirect selection favouring their implicit tuning-knob protocol. Several other molecular mechanisms comprise probable components of additional mutation protocols. Biologists might plausibly regard such mechanisms of mutation not primarily as sources of deleterious genetic mistakes but also as potentially adaptive processes for 'exploring' DNA sequence space.

Deciphering the origin of developmental stability: The role of intracellular expression variability in evolutionary conservation.

Progress in evolutionary developmental biology (evo-devo) has deepened our understanding of how intrinsic properties of embryogenesis, along with natural selection and population genetics, shape phenotypic diversity. A focal point of recent empirical and theoretical research is the idea that highly developmentally stable phenotypes are more conserved in evolution. Previously, we demonstrated that in Japanese medaka (Oryzias latipes), embryonic stages and genes with high stability, estimated through whole-embryo RNA-seq, are highly conserved in subsequent generations. However, the precise origin of the stability of gene expression levels evaluated at the whole-embryo level remained unclear. Such stability could be attributed to two distinct sources: stable intracellular expression levels or spatially stable expression patterns. Here we demonstrate that stability observed in whole-embryo RNA-seq can be attributed to stability at the cellular level (low variability in gene expression at the cellular levels). We quantified the intercellular variations in expression levels and spatial gene expression patterns for seven key genes involved in patterning dorsoventral and rostrocaudal regions during early development in medaka. We evaluated intracellular variability by counting transcripts and found its significant correlation with variation observed in whole-embryo RNA-seq data. Conversely, variation in spatial gene expression patterns, assessed through intraindividual left-right asymmetry, showed no correlation. Given the previously reported correlation between stability and conservation of expression levels throughout embryogenesis, our findings suggest a potential general trend: the stability or instability of developmental systems-and the consequent evolutionary diversity-may be primarily anchored in intrinsic fundamental elements such as the variability of intracellular states.

The Role of (Co)variation in Shaping the Response to Selection in New World Leaf-Nosed Bats.

AbstractUnderstanding and predicting the evolutionary responses of complex morphological traits to selection remains a major challenge in evolutionary biology. Because traits are genetically correlated, selection on a particular trait produces both direct effects on the distribution of that trait and indirect effects on other traits in the population. The correlations between traits can strongly impact evolutionary responses to selection and may thus impose constraints on adaptation. Here, we used museum specimens and comparative quantitative genetic approaches to investigate whether the covariation among cranial traits facilitated or constrained the response to selection during the major dietary transitions in one of the world's most ecologically diverse mammalian families-the phyllostomid bats. We reconstructed the set of net selection gradients that would have acted on each cranial trait during the major transitions to feeding specializations and decomposed the selection responses into their direct and indirect components. We found that for all transitions, most traits capturing craniofacial length evolved toward adaptive directions owing to direct selection. Additionally, we showed instances of dietary transitions in which the complex interaction between the patterns of covariation among traits and the strength and direction of selection either constrained or facilitated evolution. Our work highlights the importance of considering the within-species covariation estimates to quantify evolvability and to disentangle the relative contribution of variational constraints versus selective causes for observed patterns.

The potential for evolutionary rescue in an Arctic seashore plant threatened by climate change.

The impacts of climate change may be particularly severe for geographically isolated populations, which must adjust through plastic responses or evolve. Here, we study an endangered Arctic plant, Primula nutans ssp. finmarchica, confined to Fennoscandian seashores and showing indications of maladaptation to warming climate. We evaluate the potential of these populations to evolve to facilitate survival in the rapidly warming Arctic (i.e. evolutionary rescue) by utilizing manual crossing experiments in a nested half-sibling breeding design. We estimate G-matrices, evolvability and genetic constraints in traits with potentially conflicting selection pressures. To explicitly evaluate the potential for climate change adaptation, we infer the expected time to evolve from a northern to a southern phenotype under different selection scenarios, using demographic and climatic data to relate expected evolutionary rates to projected rates of climate change. Our results indicate that, given the nearly 10-fold greater evolvability of vegetative than of floral traits, adaptation in these traits may take place nearly in concert with changing climate, given effective climate mitigation. However, the comparatively slow expected evolutionary modification of floral traits may hamper the evolution of floral traits to track climate-induced changes in pollination environment, compromising sexual reproduction and thus reducing the likelihood of evolutionary rescue.

Vertically inherited microbiota and environment modifying behaviours conceal genetic variation in dung beetle life history.

Diverse organisms actively manipulate their (sym)biotic and physical environment in ways that feed back on their own development. However, the degree to which these processes affect microevolution remains poorly understood. The gazelle dung beetle both physically modifies its ontogenetic environment and structures its biotic interactions through vertical symbiont transmission. By experimentally eliminating (i) physical environmental modifications and (ii) the vertical inheritance of microbes, we assess how environment modifying behaviour and microbiome transmission shape heritable variation and evolutionary potential. We found that depriving larvae of symbionts and environment modifying behaviours increased additive genetic variance and heritability for development time but not body size. This suggests that larvae's ability to manipulate their environment has the potential to modify heritable variation and to facilitate the accumulation of cryptic genetic variation. This cryptic variation may become released and selectable when organisms encounter environments that are less amenable to organismal manipulation or restructuring. Our findings also suggest that intact microbiomes, which are commonly thought to increase genetic variation of their hosts, may instead reduce and conceal heritable variation. More broadly, our findings highlight that the ability of organisms to actively manipulate their environment may affect the potential of populations to evolve when encountering novel, stressful conditions.

Evolution of genome fragility enables microbial division of labor.

Division of labor can evolve when social groups benefit from the functional specialization of its members. Recently, a novel means of coordinating the division of labor was found in the antibiotic-producing bacterium Streptomyces coelicolor, where specialized cells are generated through large-scale genomic re-organization. We investigate how the evolution of a genome architecture enables such mutation-driven division of labor, using a multiscale computational model of bacterial evolution. In this model, bacterial behavior-antibiotic production or replication-is determined by the structure and composition of their genome, which encodes antibiotics, growth-promoting genes, and fragile genomic loci that can induce chromosomal deletions. We find that a genomic organization evolves, which partitions growth-promoting genes and antibiotic-coding genes into distinct parts of the genome, separated by fragile genomic loci. Mutations caused by these fragile sites mostly delete growth-promoting genes, generating sterile, and antibiotic-producing mutants from weakly-producing progenitors, in agreement with experimental observations. This division of labor enhances the competition between colonies by promoting antibiotic diversity. These results show that genomic organization can co-evolve with genomic instabilities to enable reproductive division of labor.

Nectar and floral morphology differ in evolutionary potential in novel pollination environments.

Plants can evolve rapidly after pollinator changes, but the response of different floral traits to novel selection can vary. Floral morphology is often expected to show high integration to maintain pollination accuracy, while nectar traits can be more environmentally sensitive. The relative role of genetic correlations and phenotypic plasticity (PP) in floral evolution remains unclear, particularly for nectar traits, and can be studied in the context of recent pollinator changes. Digitalis purpurea shows rapid recent evolution of corolla morphology but not nectar traits following a range expansion with hummingbirds added as pollinators. We use this species to compare PP, heritability, evolvability and integration of floral morphology and nectar in a common garden. Morphological traits showed higher heritability than nectar traits, and the proximal section of the corolla, which regulates access to nectar and underwent rapid change in introduced populations, presented lower integration than the rest of the floral phenotype. Nectar was more plastic than morphology, driven by highly plastic sugar concentration. Nectar production rate showed high potential to respond to selection. These results explain the differential rapid evolution of floral traits previously observed in this species and show how intrafloral modularity determines variable evolutionary potential in morphological and nectar traits.

Indirect genetic effects should make group size more evolvable than expected.

Group size is an important trait for many ecological and evolutionary processes. However, it is not a trait possessed by individuals but by social groups, and as many genomes contribute to group size understanding its genetic underpinnings and so predicting its evolution is a conceptual challenge. Here I suggest how group size can be modelled as a joint phenotype of multiple individuals, and so how models for evolution accounting for indirect genetic effects are essential for understanding the genetic variance of group size. This approach makes it clear that (a) group size should have a larger genetic variance than initially expected as indirect genetic effects always contribute exactly as much as direct genetic effects and (b) the response to selection of group size should be faster than expected based on direct genetic variance alone as the correlation between direct and indirect effects is always at the maximum positive limit of 1. Group size should therefore show relatively rapid evolved increases and decreases, the consequences of which and evidence for I discuss.

The Paradox of Predictability Provides a Bridge Between Micro- and Macroevolution.

The relationship between the evolutionary dynamics observed in contemporary populations (microevolution) and evolution on timescales of millions of years (macroevolution) has been a topic of considerable debate. Historically, this debate centers on inconsistencies between microevolutionary processes and macroevolutionary patterns. Here, we characterize a striking exception: emerging evidence indicates that standing variation in contemporary populations and macroevolutionary rates of phenotypic divergence are often positively correlated. This apparent consistency between micro- and macroevolution is paradoxical because it contradicts our previous understanding of phenotypic evolution and is so far unexplained. Here, we explore the prospects for bridging evolutionary timescales through an examination of this "paradox of predictability." We begin by explaining why the divergence-variance correlation is a paradox, followed by data analysis to show that the correlation is a general phenomenon across a broad range of temporal scales, from a few generations to tens of millions of years. Then we review complementary approaches from quantitative-genetics, comparative morphology, evo-devo, and paleontology to argue that they can help to address the paradox from the shared vantage point of recent work on evolvability. In conclusion, we recommend a methodological orientation that combines different kinds of short-term and long-term data using multiple analytical frameworks in an interdisciplinary research program. Such a program will increase our general understanding about how evolution works within and across timescales.

Twenty years on from Developmental Plasticity and Evolution: middle-range theories and how to test them.

In Developmental Plasticity and Evolution, Mary-Jane West-Eberhard argued that the developmental mechanisms that enable organisms to respond to their environment are fundamental causes of adaptation and diversification. Twenty years after publication of this book, this once so highly controversial claim appears to have been assimilated by a wealth of studies on 'plasticity-led' evolution. However, we suggest that the role of development in explanations for adaptive evolution remains underappreciated in this body of work. By combining concepts of evolvability from evolutionary developmental biology and quantitative genetics, we outline a framework that is more appropriate to identify developmental causes of adaptive evolution. This framework demonstrates how experimental and comparative developmental biology and physiology can be leveraged to put the role of plasticity in evolution to the test.

Analysis of proteins in the light of mutations.

Proteins have evolved through mutations-amino acid substitutions-since life appeared on Earth, some 109 years ago. The study of these phenomena has been of particular significance because of their impact on protein stability, function, and structure. This study offers a new viewpoint on how the most recent findings in these areas can be used to explore the impact of mutations on protein sequence, stability, and evolvability. Preliminary results indicate that: (1) mutations can be viewed as sensitive probes to identify 'typos' in the amino-acid sequence, and also to assess the resistance of naturally occurring proteins to unwanted sequence alterations; (2) the presence of 'typos' in the amino acid sequence, rather than being an evolutionary obstacle, could promote faster evolvability and, in turn, increase the likelihood of higher protein stability; (3) the mutation site is far more important than the substituted amino acid in terms of the marginal stability changes of the protein, and (4) the unpredictability of protein evolution at the molecular level-by mutations-exists even in the absence of epistasis effects. Finally, the Darwinian concept of evolution "descent with modification" and experimental evidence endorse one of the results of this study, which suggests that some regions of any protein sequence are susceptible to mutations while others are not. This work contributes to our general understanding of protein responses to mutations and may spur significant progress in our efforts to develop methods to accurately forecast changes in protein stability, their propensity for metamorphism, and their ability to evolve.