Evidence for Fisher's dominance theory: how many 'special cases'?

Dominance, its genetic basis and evolution has been at the heart of one of the most intense controversies in the history of genetics. For more than eighty years the existence of dominance modifiers, genetic elements controlling dominance-recessivity interactions, has been suggested as a theoretical possibility, but the modifier elements themselves have remained elusive. A recent study of the self-incompatibility locus in flowering plants provided the first empirical evidence for such genetic elements: small non-coding RNAs that control dominance-recessivity by mediating methylation of the promoter of the recessive allele. Theory has shown that several biological situations are favorable for the evolution of dominance modifiers. We argue that the elucidation of this mechanism of dominance opens up new research avenues that could lead to uncovering dominance modifiers in other genetic systems, such as genes controlling Batesian and Müllerian mimicry or host-parasite interactions, thereby shedding light on the generality of the proposed mechanism.     

Evolution of dominance in polymorphic Batesian mimicry

Models of two simple genetic systems of two alleles segregating at two loci are used to study the evolution of dominance of a Batesian mimic maintained in a population by frequency-dependent selection. The alleles at one locus determine the mimetic patterns, and their dominance is modified by the alleles at the other locus. In the model, the modifiers of dominance may themselves be either fully dominant or have additive effects on the dominance of the mimics. When the modifier is fully dominant in its effect on the dominance of a new mimic, the mimic will evolve dominance irrespective of the initial frequency of the modifier. When the modifiers act additively on the dominance of the mimics, a new mimic will evolve either dominance or recessiveness depending on the initial frequency of the modifiers. Unless the modifier is initially at quite a high frequency dominance will not evolve. And dominance will not evolve fully unless the modifiers are more or less selectively neutral in their effects on all other characters except the mimicry. The significance of these results is discussed with reference to the different dominance relations of the mimics in different races of the butterfly Papilio dardanus.     

Evolution of dominance in metabolic pathways

Dominance is a form of phenotypic robustness to mutations. Understanding how such robustness can evolve provides a window into how the relation between genotype and phenotype can evolve. As such, the issue of dominance evolution is a question about the evolution of inheritance systems. Attempts at explaining the evolution of dominance have run into two problems. One is that selection for dominance is sensitive to the frequency of heterozygotes. Accordingly, dominance cannot evolve unless special conditions lead to the presence of a high frequency of mutant alleles in the population. Second, on the basis of theoretical results in metabolic control analysis, it has been proposed that metabolic systems possess inherent constraints. These hypothetical constraints imply the default manifestation of dominance of the wild type with respect to the effects of mutations at most loci. Hence, some biologists have maintained that an evolutionary explanation is not relevant to dominance. In this article, we put into question the hypothetical assumption of default metabolic constraints. We show that this assumption is based on an exclusion of important nonlinear interactions that can occur between enzymes in a pathway. With an a priori exclusion of such interactions, the possibility of epistasis and hence dominance modification is eliminated. We present a theoretical model that integrates enzyme kinetics and population genetics to address dominance evolution in metabolic pathways. In the case of mutations that decrease enzyme concentrations, and given the mechanistic constraints of Michaelis-Menten-type catalysis, it is shown that dominance of the wild type can be extensively modified in a two-enzyme pathway. Moreover, we discuss analytical results indicating that the conclusions from the two-enzyme case can be generalized to any number of enzymes. Dominance modification is achieved chiefly through changes in enzyme concentrations or kinetic parameters such as k(cat), both of which can alter saturation levels. Low saturation translates into higher levels of dominance with respect to mutations that decrease enzyme concentrations. Furthermore, it is shown that in the two-enzyme example, dominance evolves as a by-product of selection in a manner that is insensitive to the frequency of heterozygotes. Using variation in k(cat) as an example of modifier mutations, it is shown that the latter can have direct fitness effects in addition to dominance modification effects. Dominance evolution can occur in a frequency-insensitive manner as a result of selection for such dual-effects alleles. This type of selection may prove to be a common pattern for the evolution of phenotypic robustness to mutations.     

ASSORTATIVE MATE CHOICE AND DOMINANCE MODIFICATION: ALTERNATIVE WAYS OF REMOVING HETEROZYGOTE DISADVANTAGE

In genetic polymorphisms of two alleles, heterozygous individuals may contribute to the next generation on average more or fewer descendants than the homozygotes. Two different evolutionary responses that remove a disadvantageous heterozygote phenotype from the population are the evolution of strictly assortative mate choice, and that of a modifier making one of the two alleles completely dominant. We derive invasion fitness of mutants introducing dominance or assortative mate choice in a randomly mating population with a genetic polymorphism for an ecological trait. Mutations with small effects as well as mutants introducing complete dominance or perfect assorting are considered. Using adaptive dynamics techniques, we are able to calculate the ratio of fitness gradients for the effects of a dominance modifier and a mate choice locus, near evolutionary branching points. With equal resident allele frequencies, selection for mate choice is always stronger. Dominance is more strongly selected than assortative mating when the resident (common) alleles have very unequal frequencies at equilibrium. With female mate choice the difference in frequencies where dominance is more strongly selected is smaller than when mutants of both sexes can choose without costs. A symmetric resource-competition model illustrates the results.     

Variation and selection at the CAULIFLOWER floral homeotic gene accompanying the evolution of domesticated Brassica oleracea

The evolution of plant morphologies during domestication events provides clues to the origin of crop species and the evolutionary genetics of structural diversification. The CAULIFLOWER gene, a floral regulatory locus, has been implicated in the cauliflower phenotype in both Arabidopsis thaliana and Brassica oleracea. Molecular population genetic analysis indicates that alleles carrying a nonsense mutation in exon 5 of the B. oleracea CAULIFLOWER (BoCAL) gene are segregating in both wild and domesticated B. oleracea subspecies. Alleles carrying this nonsense mutation are nearly fixed in B. oleracea ssp. botrytis (domestic cauliflower) and B. oleracea ssp. italica (broccoli), both of which show evolutionary modifications of inflorescence structures. Tests for selection indicate that the pattern of variation at this locus is consistent with positive selection at BoCAL in these two subspecies. This nonsense polymorphism, however, is also present in both B. oleracea ssp. acephala (kale) and B. oleracea ssp. oleracea (wild cabbage). These results indicate that specific alleles of BoCAL were selected by early farmers during the domestication of modified inflorescence structures in B. oleracea.     

The evolutionary dynamics of direct phenotypic overdominance: emergence possible, loss probable

An evolutionary dynamical system with explicit diploid genetics is used to investigate the likelihood of observing phenotypically overdominant heterozygotes versus heterozygous phenotypes that are intermediate between the homozygotes. In this model, body size evolves in a population with discrete demographic episodes and with competition limiting reproduction. A genotype-phenotype map for body size is used that can generate the two qualitative types of dominance interactions (overdominance versus intermediate dominance). It is written as a single-locus model with one focal locus and parameters summarizing the effects of alleles at other loci. Two types of evolutionarily stable strategy (ESS; continuously stable strategy, CSS) occur. The ESS is generated either (1) by the population ecology; or (2) by a local maximum of the genotype-phenotype map. Overdominant heterozygotes are expected to arise if the population evolves toward the second type of ESS, where nearly maximum body sizes are found. When other loci with partially dominant inheritance also evolve, the location of the maximum in the genotype-phenotype map repeatedly changes. It is unlikely that an evolving population will track these changes; ESSs of the second type now are at best quasi-stationary states of the evolutionary dynamics. Considering the restrictions on its probability, a pattern of phenotypic overdominance is expected to be rare.     

Allelic divergence precedes and promotes gene duplication

One of the striking observations from recent whole-genome comparisons is that changes in the number of specialized genes in existing gene families, as opposed to novel taxon-specific gene families, are responsible for the majority of the difference in genome composition between major taxa. Previous models of duplicate gene evolution focused primarily on the role that neutral processes can play in evolutionary divergence after the duplicates are already fixed in the population. By instead including the entire cycle of duplication and divergence, we show that specialized functions are most likely to evolve through strong selection acting on segregating alleles at a single locus, even before the duplicate arises. We show that the fitness relationships that allow divergent alleles to evolve at a single locus largely overlap with the conditions that allow divergence of previously duplicated genes. Thus, a solution to the paradox of the origin of organismal complexity via the expansion of gene families exists in the form of the deterministic spread of novel duplicates via natural selection.     

Unresolved boundaries of evolutionary theory and the question of how inheritance systems evolve: 75 years of debate on the evolution of dominance

One of the key issues in the evolution of life is the evolution of inheritance systems. In population genetics, the earliest attempt at addressing the latter problem revolved around Fisher's theory on the evolution of dominance. Fisher's hypothesis was that inheritance systems could be modified during the evolutionary process in such a way that wild-type phenotypes could become dominant with respect to mutant phenotypes. This would result in the buffering of a population against the deleterious effects of mutations. The debate that ensued on this topic has been one of the most longstanding in evolutionary theory. At present, the prevalent view is that dominance cannot evolve as a direct result of selection. Furthermore, it has been argued that due to inherent constraints in biochemical systems, the manifestation of dominance is a default expectation and hence evolutionary explanations are not necessary. This has led to the position that the subject is generally resolved and no further debate is necessary. However, there are also several studies indicating that dominance levels can be modified as a result of changes in the genetic background. Furthermore, other studies have indicated that dominance selection is possible in certain circumstances. To a large degree, conclusions from both of the latter types of studies have been ignored. In this article, the history of several intellectual and methodological traditions that have contributed to this debate are traced, including experimental genetics, theoretical population genetics and theoretical biochemistry. In the light of both old and contemporary works on this topic, it is argued that contrary to the prevalent view, the evolution of dominance is not a resolved issue. A re-examination of this issue is essential, given that dominance evolution is likely to be an important stepping stone towards understanding the evolution of inheritance systems.     

Molecular mechanisms of dominance evolution in Müllerian mimicry

Natural selection acting on dominance between adaptive alleles at polymorphic loci can be sufficiently strong for dominance to evolve. However, the molecular mechanisms underlying such evolution are generally unknown. Here, using Müllerian mimicry as a case‐study for adaptive morphological variation, we present a theoretical analysis of the invasion of dominance modifiers altering gene expression through different molecular mechanisms. Toxic species involved in Müllerian mimicry exhibit warning coloration, and converge morphologically with other toxic species of the local community, due to positive frequency‐dependent selection acting on these colorations. Polymorphism in warning coloration may be maintained by migration–selection balance with fine scale spatial heterogeneity. We modeled a dominance modifier locus altering the expression of the warning coloration locus, targeting one or several alleles, acting in cis or trans, and either enhancing or repressing expression. We confirmed that dominance could evolve when balanced polymorphism was maintained at the color locus. Dominance evolution could result from modifiers enhancing one allele specifically, irrespective of their linkage with the targeted locus. Nonspecific enhancers could also persist in populations, at frequencies tightly depending on their linkage with the targeted locus. Altogether, our results identify which mechanisms of expression alteration could lead to dominance evolution in polymorphic mimicry.     

EVOLUTION OF DISPERSAL RATES IN METAPOPULATION MODELS: BRANCHING AND CYCLIC DYNAMICS IN PHENOTYPE SPACE

We study the evolution of dispersal rates in a two patch metapopulation model. The local dynamics in each patch are given by difference equations, which, together with the rate of dispersal between the patches, determine the ecological dynamics of the metapopulation. We assume that phenotypes are given by their dispersal rate. The evolutionary dynamics in phenotype space are determined by invasion exponents, which describe whether a mutant can invade a given resident population. If the resident metapopulation is at a stable equilibrium, then selection on dispersal rates is neutral if the population sizes in the two patches are the same, while selection drives dispersal rates to zero if the local abundances are different. With non-equilibrium metapopulation dynamics, non-zero dispersal rates can be maintained by selection. In this case, and if the patches are ecologically identical, dispersal rates always evolve to values which induce synchronized metapopulation dynamics. If the patches are ecologically different, evolutionary branching into two coexisting dispersal phenotypes can be observed. Such branching can happen repeatedly, leading to polymorphisms with more than two phenotypes. If there is a cost to dispersal, evolutionary cycling in phenotype space can occur due to the dependence of selection pressures on the ecological attractor of the resident population, or because phenotypic branching alternates with the extinction of one of the branches. Our results extend those of Holt and McPeek (1996), and suggest that phenotypic branching is an important evolutionary process. This process may be relevant for sympatric speciation.     

The integrative biology of genetic dominance

Dominance is a basic property of inheritance systems describing the link between a diploid genotype at a single locus and the resulting phenotype. Models for the evolution of dominance have long been framed as an opposition between the irreconcilable views of Fisher in 1928 supporting the role of largely elusive dominance modifiers and Wright in 1929, who viewed dominance as an emerging property of the structure of enzymatic pathways. Recent theoretical and empirical advances however suggest that these opposing views can be reconciled, notably using models investigating the regulation of gene expression and developmental processes. In this more comprehensive framework, phenotypic dominance emerges from departures from linearity between any levels of integration in the genotype-to-phenotype map. Here, we review how these different models illuminate the emergence and evolution of dominance. We then detail recent empirical studies shedding new light on the diversity of molecular and physiological mechanisms underlying dominance and its evolution. By reconciling population genetics and functional biology, we hope our review will facilitate cross-talk among research fields in the integrative study of dominance evolution.     

Demography can favour female-advantageous alleles

When female fecundity is relatively independent of male abundance, while male reproduction is proportional to female abundance, females have a larger effect on population dynamics than males (i.e. female demographic dominance). This population dynamic phenomenon might not appear to influence evolution, because male and female genomes still contribute equally much to the next generation. However, here we examine two evolutionary scenarios to provide a proof of principle that spatial structure can make female demographic dominance matter. Our two simulation models combine dispersal evolution with local adaptation subjected to intralocus sexual conflict and environmentally driven sex ratio biases, respectively. Both models have equilibria where one environment (without being intrinsically poorer) has so few reproductive females that trait evolution becomes disproportionately determined by those environments where females survive better (intralocus sexual conflict model), or where daughters are overproduced (environmental sex determination model). Surprisingly, however, the two facts that selection favours alleles that benefit females, and population growth is improved when female fitness is high, together do not imply that all measures of population performance are improved. The sex-specificity of the source–sink dynamics predicts that populations can evolve to fail to persist in habitats where alleles do poorly when expressed in females.     

Sporophytic self-incompatibility in Senecio squalidus (Asteraceae): S allele dominance interactions and modifiers of cross-compatibility and selfing rates

Understanding genetic mechanisms of self-incompatibility (SI) and how they evolve is central to understanding the mating behaviour of most outbreeding angiosperms. Sporophytic SI (SSI) is controlled by a single multi-allelic locus, S, which is expressed in the diploid (sporophyte) plant to determine the SI phenotype of its haploid (gametophyte) pollen. This allows complex patterns of independent S allele dominance interactions in male (pollen) and female (pistil) reproductive tissues. Senecio squalidus is a useful model for studying the genetic regulation and evolution of SSI because of its population history as an alien invasive species in the UK. S. squalidus maintains a small number of S alleles (7–11) with a high frequency of dominance interactions. Some S. squalidus individuals also show partial selfing and/or greater levels of cross-compatibility than expected under SSI. We previously speculated that these might be adaptations to invasiveness. Here we describe a detailed characterization of the regulation of SSI in S. squalidus. Controlled crosses were used to determine the S allele dominance hierarchy of six S alleles and effects of modifiers on cross-compatibility and partial selfing. Complex dominance interactions among S alleles were found with at least three levels of dominance and tissue-specific codominance. Evidence for S gene modifiers that increase selfing and/or cross-compatibility was also found. These empirical findings are discussed in the context of theoretical predictions for maintenance of S allele dominance interactions, and the role of modifier loci in the evolution of SI.     

The resolution of sexual antagonism by gene duplication

Disruptive selection between males and females can generate sexual antagonism, where alleles improving fitness in one sex reduce fitness in the other. This type of genetic conflict arises because males and females carry nearly identical sets of genes: opposing selection, followed by genetic mixing during reproduction, generates a population genetic "tug-of-war" that constrains adaptation in either sex. Recent verbal models suggest that gene duplication and sex-specific cooption of paralogs might resolve sexual antagonism and facilitate evolutionary divergence between the sexes. However, this intuitive proximal solution for sexual dimorphism potentially belies a complex interaction between mutation, genetic drift, and positive selection during duplicate fixation and sex-specific paralog differentiation. The interaction of these processes--within the explicit context of duplication and sexual antagonism--has yet to be formally described by population genetics theory. Here, we develop and analyze models of gene duplication and sex-specific differentiation between paralogs. We show that sexual antagonism can favor the fixation and maintenance of gene duplicates, eventually leading to the evolution of sexually dimorphic genetic architectures for male and female traits. The timescale for these evolutionary transitions is sensitive to a suite of genetic and demographic variables, including allelic dominance, recombination, sex linkage, and population size. Interestingly, we find that female-beneficial duplicates preferentially accumulate on the X chromosome, whereas male-beneficial duplicates are biased toward autosomes, independent of the dominance parameters of sexually antagonistic alleles. Although this result differs from previous models of sexual antagonism, it is consistent with several findings from the empirical genomics literature.     

PHYSIOLOGICAL AND BEHAVIORAL ADAPTATION TO VARYING ENVIRONMENTS: A MATHEMATICAL MODEL

We develop a mathematical model to explore the evolution of habitat selection and physiological adaptation in a heterogeneous environment. The model assumes the following conditions: 1) a panmictic population of infinite size; 2) prereproductive individuals mobile enough to move between patches; 3) alleles at one locus code for absence or presence of adaptation to detrimental patches; 4) alleles at a second locus code for absence or presence of behavior(s) that cause avoidance of the detrimental patches; 5) additive effects of alleles controlling physiology and behavior; 6) frequency-independent fitness. Results of the model indicate that nontrivial, polymorphic equilibria do not exist. The pattern of genotypic fitnesses and the initial allelic frequencies can influence whether the population adapts by physiological or behavioral mechanisms, or by both. Linkage between the two loci can alter the outcome of evolution, given specified genotypic fitness values and initial allelic frequencies.     

QTL mapping of inbreeding-related cold sensitivity and conditional lethality in Drosophila melanogaster

Inbreeding depression is a central theme within genetics, and is of specific interest for researchers within evolutionary and conservation genetics and animal and plant breeding. Inbreeding effects are thought to be caused by the joint expression of conditional and unconditional deleterious alleles. Whenever the expression of deleterious alleles is conditional, this can result in extreme environmental sensitivity in certain inbred lineages. Analysis of conditional lethal effects can reveal some of the loci that are sensitive to inbreeding. We performed a QTL (quantitative trait locus) mapping study of inbreeding-related and conditionally expressed lethality in Drosophila melanogaster. The lethal effect was triggered by exposure to a cold shock. We used a North Carolina crossing Design 3 to establish the mapping population, as well as to estimate the average dominance ratio and heritability. We found two QTL on the major autosomes carrying recessive lethals that caused male mortality, one of which also affected female mortality. More detailed study of these loci will provide information on the mechanistic basis and environmental sensitivity of inbreeding depression.     

Duplication polymorphism at MHC class II DRB1 locus in the wild boar (<Emphasis Type="Italic">Sus scrofa</Emphasis>)

The origin of allelic polymorphism in genes of the major histocompatibility complex represents a central topic in evolutionary genetics as it is probably the most polymorphic region in the nuclear genome of vertebrates. Accordingly, the analyses of genetic variability at these loci provide evidence complementary to the population genetics studies based on neutral loci. In this study, four wild boar populations, two from Italy (Florence region and Castelporziano Presidential Reserve, outside Rome) and one each from Hungary and Poland, were characterized at a highly polymorphic fragment including part of intron 1 and exon 2 of swine leukocyte antigen (SLA) class II DRB1 gene by direct sequencing and by cloning. Excluding the false alleles, a total of 18 different sequences were observed in 57 individuals. The high ratio of nonsynonymous (dN) vs synonymous (dS) substitution rates in the peptide-binding region supports the hypothesis that balancing selection is operating at this locus. A duplication event at the DRB1 gene was documented only in one Italian population with both copies being putatively active. This is the first evidence of a polymorphism for the number of copies of an SLA gene.     

Sex ratio polymorphism: The impact of mutation and drift on evolution

This paper addresses the question, which sex ratio will evolve in a population that is subject to mutation and drift. The problem is analyzed using a simulation model as well as analytical methods. A detailed simulation model for the evolution of a population's allele distribution shows that for the sex ratio game a wide spectrum of different population states may evolve from on the one hand a monomorphic state with one predominant allele and with all other alleles suppressed by the forces of selection, to on the other hand a polymorphism determined by recurrent mutations. Which of these states will evolve depends on the population size, the mating system and the rate of mutations. For the sex ratio game the evolutionary stable strategy (ESS), as defined by evolutionary game theory, can only predict the population sex ratio but not the underlying stable population state. A comparison of different approaches to the problem shows that false predictions of the stable population states might result from two simplifying assumptions that are fairly common in evolutionary biology: a) it is assumed that mutations are rare events and there is never more than one mutant gene present in a population at any one time; b) a deterministic relationship is assumed between the fitness assigned to an individual's strategy and the individual's contribution to the gene pool of future generations.