Genetic Canalization Research Articles

Genetic Assimilation and the Postcolonization Erosion of Phenotypic Plasticity in Island Tiger Snakes

In 1942, C.H. Waddington [1] suggested that colonizing populations could initially succeed by flexibly altering their characteristics (phenotypic plasticity; [2-4]) in fitness-inducing traits, but selective forces would rapidly eliminate that plasticity to result in a canalized trait [1, 5, 6]. Waddington termed this process "genetic assimilation"[1, 7]. Despite the potential importance of genetic assimilation to evolutionary changes in founder populations [8-10], empirical evidence on this topic is rare, possibly because it happens on short timescales and is therefore difficult to detect except under unusual circumstances [11, 12]. We exploited a mosaic of snake populations isolated (or introduced) on islands from less than 30 years ago to more than 9000 years ago and exposed to selection for increased head size (i.e., ability to ingest large prey [13-16]). Here we show that a larger head size is achieved by plasticity in "young" populations and by genetic canalization in "older" populations. Island tiger snakes (Notechis scutatus) thus show clear empirical evidence of genetic assimilation, with the elaboration of an adaptive trait shifting from phenotypically plastic expression through to canalization within a few thousand years.

The thrifty epigenotype: An acquired and heritable predisposition for obesity and diabetes?

Obesity and type 2 diabetes arise from a set of complex gene-environment interactions. Explanations for the heritability of these syndromes and the environmental contribution to disease susceptibility are addressed by the "thrifty genotype" and the "thrifty phenotype" hypotheses. Here, the merits of both models are discussed and elements of them are used to synthesize a "thrifty epigenotype" hypothesis. I propose that: (1) metabolic thrift, the capacity for efficient acquisition, storage and use of energy, is an ancient, complex trait, (2) the environmentally responsive gene network encoding this trait is subject to genetic canalization and thereby has become robust against mutational perturbations, (3) DNA sequence polymorphisms play a minor role in the aetiology of obesity and type 2 diabetes-instead, disease susceptibility is predominantly determined by epigenetic variations, (4) corresponding epigenotypes have the potential to be inherited across generations, and (5) Leptin is a candidate gene for the acquisition of a thrifty epigenotype.

Canalization Breakdown and Evolution in a Source‐Sink System

Understanding the process of adaptation to novel environments may help to elucidate several ecological phenomena, from the stability of species range margins to host-pathogen specificity and persistence in degraded habitats. We study evolution in one type of novel environment: a sink habitat where populations cannot persist without recurrent immigration from a source population. Previous studies on source-sink evolution have focused on how extrinsic environmental factors influence adaptation to a sink, but few studies have examined how intrinsic genetic factors influence adaptation. We use an individual-based model to explore how genetic canalization that evolves in gene regulation networks influences the adaptation of a population to a sink. We find that as canalization in the regulation network increases, the probability of adaptation to the novel habitat decreases. When adaptation to the habitat does occur, it is usually preceded by a breakdown of canalization. As evolution continues in the novel habitat, canalization reemerges, but a legacy of the breakdown may remain, even after several generations. We also find that environmental noise tends to increase the probability of adaptation to the novel habitat. Our results suggest that the details of genetic architecture can significantly influence the likelihood of niche evolution in novel environments.

Mutations leading to loss of sporulation ability in Bacillus subtilis are sufficiently frequent to favor genetic canalization.

We measured the rate of mutations impairing sporulation ability in Bacillus subtilis as 0.003 in a mutator population, following 6000 generations of strong selection for sporulation that have previously been described. This means that the product of the population size and the functional mutation rate is approximately 10(5), well within the parameter range for which genetic canalization of sporulation ability is expected.

The Evolutionary Genetics of Canalization

Evolutionary genetics has recently made enormous progress in understanding how genetic variation maps into phenotypic variation. However why some traits are phenotypically invariant despite apparent genetic and environmental changes has remained a major puzzle. In the 1940s, Conrad Hal Waddington coined the concept and term "canalization" to describe the robustness of phenotypes to perturbation; a similar concept was proposed by Waddington's contemporary Ivan Ivanovich Schmalhausen. This paper reviews what has been learned about canalization since Waddington. Canalization implies that a genotype's phenotype remains relatively invariant when individuals of a particular genotype are exposed to different environments (environmental canalization) or when individuals of the same single- or multilocus genotype differ in their genetic background (genetic canalization). Consequently, genetic canalization can be viewed as a particular kind of epistasis, and environmental canalization and phenotypic plasticity are two aspects of the same phenomenon. Canalization results in the accumulation of phenotypically cryptic genetic variation, which can be released after a "decanalizing" event. Thus, canalized genotypes maintain a cryptic potential for expressing particular phenotypes, which are only uncovered under particular decanalizing environmental or genetic conditions. Selection may then act on this newly released genetic variation. The accumulation of cryptic genetic variation by canalization may therefore increase evolvability at the population level by leading to phenotypic diversification under decanalizing conditions. On the other hand, under canalizing conditions, a major part of the segregating genetic variation may remain phenotypically cryptic; canalization may therefore, at least temporarily, constrain phenotypic evolution. Mechanistically, canalization can be understood in terms of transmission patterns, such as epistasis, pleiotropy, and genotype by environment interactions, and in terms of genetic redundancy, modularity, and emergent properties of gene networks and biochemical pathways. While different forms of selection can favor canalization, the requirements for its evolution are typically rather restrictive. Although there are several methods to detect canalization, there are still serious problems with unambiguously demonstrating canalization, particularly its adaptive value.

A STUDY OF CANALIZATION AND DEVELOPMENTAL STABILITY IN THE STERNOPLEURAL BRISTLE SYSTEM OF DROSOPHILA MELANOGASTER

Among the explanations for minimizing the effects of extraneous variation has been canalization and developmental stability. However, there is little agreement as to whether these two processes reflect a common set of mechanisms. This confusion is inflated due to the lack of consensus as to a precise definition of canalization. In this study, canalization in the sternopleural bristle system is used to investigate the relationships between measures of canalization and developmental stability by comparing how a panel of naturally derived lines responds to both genetic and environmental perturbations. No evidence for a common mechanism between the different measures of canalization was observed. Furthermore, a hypothesis regarding a common mechanism for environmental and genetic canalization was tested, and no evidence was found to support it. However, there is evidence for a relationship between at least one form of canalization and developmental stability.

Evidence for canalization of Distal‐less function in the leg of Drosophila melanogaster

A considerable body of theory pertaining to the evolution of canalization has emerged recently, yet there have been few empirical investigations of their predictions. To address this, patterns of canalization and trait correlation were investigated under the individual and joint effects of the introgression of a loss-of-function allele of the Distal-less gene and high-temperature stress on a panel of iso-female lines. Variation was examined for number of sex comb teeth and the length of the basi-tarsus on the pro-thoracic leg of male Drosophila melanogaster. I demonstrate that whereas there is evidence for trait canalization, there is no evidence to support the hypothesis of the evolution of genetic canalization as a response to microenvironmental canalization. Furthermore, I demonstrate that although there are genetic correlations between these traits, there is no association between their measures of canalization. I discuss the prospects of the evolutionary lability of the Distal-less gene within the context of changes in genetic variation and covariation.

The Opportunity for Canalization and the Evolution of Genetic Networks

There has been a recent revival of interest in how genetic interactions evolve, spurred on by an increase in our knowledge of genetic interactions at the molecular level. Empirical work on genetic networks has revealed a surprising amount of robustness to perturbations, suggesting that robustness is an evolved feature of genetic networks. Here, we derive a general model for the evolution of canalization that can incorporate any form of perturbation. We establish an upper bound to the strength of selection on canalization that is approximately equal to the fitness load in the system. This method makes it possible to compare different forms of perturbation, including genetic, developmental, and environmental effects. In general, load that arises from mutational processes is low because the mutation rate is itself low. Mutation load can create selection for canalization in a small network that can be achieved through dominance evolution or gene duplication, and in each case selection for canalization is weak at best. In larger genetic networks, selection on genetic canalization can be reasonably strong because larger networks have higher mutational load. Because load induced through migration, segregation, developmental noise, and environmental variance is not mutation limited, each can cause strong selection for canalization.

A STUDY OF CANALIZATION AND DEVELOPMENTAL STABILITY IN THE STERNOPLEURAL BRISTLE SYSTEM OF DROSOPHILA MELANOGASTER

Among the explanations for minimizing the effects of extraneous variation has been canalization and developmental stability. However, there is little agreement as to whether these two processes reflect a common set of mechanisms. This confusion is inflated due to the lack of consensus as to a precise definition of canalization. In this study, canalization in the sternopleural bristle system is used to investigate the relationships between measures of canalization and developmental stability by comparing how a panel of naturally derived lines responds to both genetic and environmental perturbations. No evidence for a common mechanism between the different measures of canalization was observed. Furthermore, a hypothesis regarding a common mechanism for environmental and genetic canalization was tested, and no evidence was found to support it. However, there is evidence for a relationship between at least one form of canalization and developmental stability.

Genetics and geometry of canalization and developmental stability in Drosophila subobscura

BackgroundMany properties of organisms show great robustness against genetic and environmental perturbations. The terms canalization and developmental stability were originally proposed to describe the ability of an organism to resist perturbations and to produce a predictable target phenotype regardless of random developmental noise. However, the extent to which canalization and developmental stability are controlled by the same set of genes and share underlying regulatory mechanisms is largely unresolved.ResultsWe have analyzed the effects of clinal genetic variation (inversion polymorphism) on wing asymmetry by applying the methods of geometric morphometrics in the context of quantitative genetics using isochromosomal lines of Drosophila subobscura. For the analysis of overall size, developmental stability was positively correlated with levels of heterozygosity and development at the optimal temperature. For analyses of shape, the overall comparisons by matrix correlations indicate that inter- and intraindividual variation levels were poorly correlated, a result also supported when comparing the vectors describing patterns of variation of landmark position. The lack of similarity was basically due to the discrepancy between the genetic and environmental components of the interindividual variation. Finally, the analyses have also underscored the presence of genetic variation for directional asymmetry.ConclusionsThe results strongly support the hypothesis that environmental canalization and developmental stability share underlying regulatory mechanisms, but environmental and genetic canalization are not functionally the same. A likely explanation for this lack of association is that natural wing shape variation in Drosophila populations is loosely related to individual fitness.

Fifty years later: I. Michael Lerner'sGenetic Homeostasis (1954)—a valiant attempt to integrate genes, organisms and environment

Although it elicited considerable discussion, Genetic Homeostasis by (I)sadore Michael Lerner, published in 1954, does not occupy a position as one of the seminal works in population genetics, the integration of genetics and environment or in evolutionary developmental biology, nor, despite its context and avowed intention, is it seen to provide the crucial mechanistic link between Waddingtonian genetic assimilation, canalization, genetics (heterozygosity), phenotypic change and selection. Why is that? A slim book of 134 five and a half by nine inch pages (more or less Royal Octavo), Genetic Homeostasis was written between January and July 1953 by a 42-year-old Professor of Poultry Science from the University of California at Berkeley; see below. Supported by a Guggenheim Fellowship, Lerner wrote the book at the Institute of Genetics at the University of Pavia, Italy and completed it at the Istituto Italiano di Idrobiologia in Pallanza. This was not Lerner’s first bookFPopulation Genetics and Animal Improvement was published in 1950Fnor would it be his last. He wrote The Genetic Basis of Selection (1959), a broadbased book for professionals, and Heredity Evolution and Society (1968), a wonderfully accessible book aimed at the more general readerFbut it is the most original and innovative of Lerner’s books, a testament to what can emerge from the combination of a prepared mind, sabbatical leave, ‘‘Guggenheim’’, solitude and an Italian winter.

The Opportunity for Canalization and the Evolution of Genetic Networks

There has been a recent revival of interest in how genetic interactions evolve, spurred on by an increase in our knowledge of genetic interactions at the molecular level. Empirical work on genetic networks has revealed a surprising amount of robustness to perturbations, suggesting that robustness is an evolved feature of genetic networks. Here, we derive a general model for the evolution of canalization that can incorporate any form of perturbation. We establish an upper bound to the strength of selection on canalization that is approximately equal to the fitness load in the system. This method makes it possible to compare different forms of perturbation, including genetic, developmental, and environmental effects. In general, load that arises from mutational processes is low because the mutation rate is itself low. Mutation load can create selection for canalization in a small network that can be achieved through dominance evolution or gene duplication, and in each case selection for canalization is weak at best. In larger genetic networks, selection on genetic canalization can be reasonably strong because larger networks have higher mutational load. Because load induced through migration, segregation, developmental noise, and environmental variance is not mutation limited, each can cause strong selection for canalization.

The population genetic theory of hidden variation and genetic robustness.

One of the most solid generalizations of transmission genetics is that the phenotypic variance of populations carrying a major mutation is increased relative to the wild type. At least some part of this higher variance is genetic and due to release of previously hidden variation. Similarly, stressful environments also lead to the expression of hidden variation. These two observations have been considered as evidence that the wild type has evolved robustness against genetic variation, i.e., genetic canalization. In this article we present a general model for the interaction of a major mutation or a novel environment with the additive genetic basis of a quantitative character under stabilizing selection. We introduce an approximation to the genetic variance in mutation-selection-drift balance that includes the previously used stochastic Gaussian and house-of-cards approximations as limiting cases. We then show that the release of hidden genetic variation is a generic property of models with epistasis or genotype-environment interaction, regardless of whether the wild-type genotype is canalized or not. As a consequence, the additive genetic variance increases upon a change in the environment or the genetic background even if the mutant character state is as robust as the wild-type character. Estimates show that this predicted increase can be considerable, in particular in large populations and if there are conditionally neutral alleles at the loci underlying the trait. A brief review of the relevant literature suggests that the assumptions of this model are likely to be generic for polygenic traits. We conclude that the release of hidden genetic variance due to a major mutation or environmental stress does not demonstrate canalization of the wild-type genotype.

Quantitative trait symmetry independent of Hsp90 buffering: distinct modes of genetic canalization and developmental stability.

The Hsp90 chaperone buffers development against a wide range of morphological changes in many organisms and in Drosophila masks the effects of hidden genetic variation. Theory predicts that genetic and nongenetic buffering will share common mechanisms. For example, it is argued that Hsp90 genetic buffering evolved solely as a by-product of environmental buffering, and that Hsp90 should mask morphological deviations from any source. To test this idea, we examined the effect of Hsp90 on purely nongenetic variation in phenotype, measured as differences between the left and right sides of several bilaterally symmetrical bristle and wing traits in individual flies. Consistent with previous reports, Hsp90 buffered the expression of rare morphogenic variants specific to particular genetic backgrounds. However, neither trait-by-trait nor global asymmetry was affected in outbred flies treated with an Hsp90 inhibitor or across a series of inbred genetic backgrounds from a wild population tested in isogenic F1 heterozygotes carrying either (i) a dominant negative Hsp90 allele on a mutant 3rd chromosome or (ii) a null P-insertion mutation, which was introgressed into the control genetic background on all chromosomes. By contrast, Hsp90-regulated trait means and significant effects of sex, temperature, and genetic background on trait symmetry were clearly detected. We conclude that, by maintaining the function of signaling proteins, Hsp90 masks variation affecting target pathways and traits in populations independent of purely nongenetic sources of variation, refuting the idea that a single Hsp90-dependent process generally controls genetic canalization and developmental stability.

Plasticity, instability and canalization: is the phenotypic variation in seedlings of sclerophyll oaks consistent with the environmental unpredictability of Mediterranean ecosystems?

• Evergreen oaks from the Mediterranean basin exhibit a conservative resource-use strategy based on a reduced expression of phenotypic variation (i.e. canalization). We hypothesized that genetic variation across closely related species is more canalized than the response to environmental variation. • Seedlings of Quercus ilex and Q. coccifera, two important oak species from the Mediterranean basin that belong to the same subgenus and section, were grown in contrasted light and nutrient environments following a factorial design. Phenotypic variation was explored in a total of 75 variables including photosynthetic capacity, nutrient allocation, allometric relationships and crown architecture. • Path analysis showed that phenotypic variation was not significantly affected by differences between species but by those between and within environments, which are argued to be primarily linked to phenotypic plasticity and developmental instability, respectively. This finding is interpreted as evidence of genetic canalization across species. • The similar importance of plasticity and instability as sources of phenotypic variation and the high degree of genetic canalization are consistent with the expected role of the environmental unpredictability of Mediterranean ecosystems in shaping the developmental patterns of these two species.

2M1415 同所的種分化過程に於ける表現型可塑性と遺伝型安定性と動的関係(20.生命の起源・進化,一般演題,日本生物物理学会第40回年会)

2M1415 同所的種分化過程に於ける表現型可塑性と遺伝型安定性と動的関係(20.生命の起源・進化,一般演題,日本生物物理学会第40回年会)

Modeling Genetic Architecture: A Multilinear Theory of Gene Interaction

The map from genotype to phenotype is an exceedingly complex function of central importance in biology. In this work we derive and analyze a mathematically tractable model of the genotype–phenotype map that allows for any order of gene interaction. By assuming that the alterations of the effect of a gene substitution due to changes in the genetic background can be described as a linear transformation, we show that the genotype–phenotype map is a sum of linear and multilinear terms of operationally defined “reference” effects at each locus. The “multilinear” model is used to study the effect of epistasis on quantitative genetic variation, on the response to selection, and on genetic canalization. It is shown how the model can be used to estimate the strength of “functional” epistasis from a variety of genetic experiments.

The evolution of genetic canalization under fluctuating selection.

If the direction of selection changes from generation to generation, the ability to respond to selection is maladaptive: the response to selection in one generation leads to reduced fitness in the next. Because the response is determined by the amount of genetic variance expressed at the phenotypic level, rapidly fluctuating selection should favor modifier genes that reduce the phenotypic effect of alleles segregating at structural loci underlying the trait. Such reduction in phenotypic expression of genetic variation has been named "genetic canalization." I support this argument with a series of two- and multilocus models with alternating linear selection and Gaussian selection with fluctuating optimum. A canalizing modifier gene affects the fitness of its carriers in three ways: (1) it reduces the phenotypic consequences of genetic response to previous selection; (2) it reduces the genetic response to selection, which is manifested as linkage disequilibrium between the modifier and structural loci; and (3) it reduces the phenotypic variance. The first two effects reduce fitness under directional selection sustained for several generations, but improve fitness when the direction of selection has just been reversed. The net effect tends to favor a canalizing modifier under rapidly fluctuating selection regimes (period of eight generations or less). The third effect improves fitness of the modifier allele if the fitness function is convex and reduces it if the function is concave. Under fluctuating Gaussian selection, the population is more likely to experience the concave portion of the fitness function when selection is stronger. Therefore, only weak to moderately strong fluctuating Gaussian selection favors genetic canalization. This paper considerably broadens the conditions that favor genetic canalization, which so far has only been postulated to evolve under long-term stabilizing selection.

Plasticity, evolvability, and modularity in RNA.

RNA folding from sequences into secondary structures is a simple yet powerful, biophysically grounded model of a genotype-phenotype map in which concepts like plasticity, evolvability, epistasis, and modularity can not only be precisely defined and statistically measured but also reveal simultaneous and profoundly non-independent effects of natural selection. Molecular plasticity is viewed here as the capacity of an RNA sequence to assume a variety of energetically favorable shapes by equilibrating among them at constant temperature. Through simulations based on experimental designs, we study the dynamics of a population of RNA molecules that evolve toward a predefined target shape in a constant environment. Each shape in the plastic repertoire of a sequence contributes to the overall fitness of the sequence in proportion to the time the sequence spends in that shape. Plasticity is costly, since the more shapes a sequence can assume, the less time it spends in any one of them. Unsurprisingly, selection leads to a reduction of plasticity (environmental canalization). The most striking observation, however, is the simultaneous slow-down and eventual halting of the evolutionary process. The reduction of plasticity entails genetic canalization, that is, a dramatic loss of variability (and hence a loss of evolvability) to the point of lock-in. The causal bridge between environmental canalization and genetic canalization is provided by a correlation between the set of shapes in the plastic repertoire of a sequence and the set of dominant (minimum free energy) shapes in its genetic neighborhood. This statistical property of the RNA genotype-phenotype map, which we call plastogenetic congruence, traps populations in regions where most genetic variation is phenotypically neutral. We call this phenomenon neutral confinement. Analytical models of neutral confinement, made tractable by the assumption of perfect plastogenetic congruence, formally connect mutation rate, the topography of phenotype space, and evolvability. These models identify three mutational regimes: that corresponding to neutral confinement, an exploration threshold corresponding to a breakdown of neutral confinement with the simultaneous persistence of the dominant phenotype, and a classic error threshold corresponding to the loss of the dominant phenotype. In a final step, we analyze the structural properties of canalized phenotypes. The reduction of plasticity leads to extreme modularity, which we analyze from several perspectives: thermophysical (melting--the RNA version of a norm of reaction), kinetic (folding pathways--the RNA version of development), and genetic (transposability--the insensitivity to genetic context). The model thereby suggests a possible evolutionary origin of modularity as a side effect of environmental canalization.

THE EVOLUTION OF GENETIC CANALIZATION UNDER FLUCTUATING SELECTION

If the direction of selection changes from generation to generation, the ability to respond to selection is maladaptive: the response to selection in one generation leads to reduced fitness in the next. Because the response is determined by the amount of genetic variance expressed at the phenotypic level, rapidly fluctuating selection should favor modifier genes that reduce the phenotypic effect of alleles segregating at structural loci underlying the trait. Such reduction in phenotypic expression of genetic variation has been named “genetic canalization.” I support this argument with a series of two- and multilocus models with alternating linear selection and Gaussian selection with fluctuating optimum. A canalizing modifier gene affects the fitness of its carriers in three ways: (1) it reduces the phenotypic consequences of genetic response to previous selection; (2) it reduces the genetic response to selection, which is manifested as linkage disequilibrium between the modifier and structural loci; and (3) it reduces the phenotypic variance. The first two effects reduce fitness under directional selection sustained for several generations, but improve fitness when the direction of selection has just been reversed. The net effect tends to favor a canalizing modifier under rapidly fluctuating selection regimes (period of eight generations or less). The third effect improves fitness of the modifier allele if the fitness function is convex and reduces it if the function is concave. Under fluctuating Gaussian selection, the population is more likely to experience the concave portion of the fitness function when selection is stronger. Therefore, only weak to moderately strong fluctuating Gaussian selection favors genetic canalization. This paper considerably broadens the conditions that favor genetic canalization, which so far has only been postulated to evolve under long-term stabilizing selection.Corresponding Editor: T. Mousseau