An evolutionary framework for common diseases: the ancestral-susceptibility model

Unlike rare mendelian diseases, which are due to new mutations (i.e. derived alleles), several alleles that increase the risk to common diseases are ancestral. Moreover, population genetics studies suggest that some derived alleles that protect against common diseases became advantageous recently. These observations can be explained within an evolutionary framework in which ancestral alleles reflect ancient adaptations to the lifestyle of ancient human populations, whereas the derived alleles were deleterious. However, with the shift in environment and lifestyle, the ancestral alleles now increase the risk of common diseases in modern populations. In this article, we develop an explicit evolutionary model and use population genetics simulations to investigate the expected haplotype structure and type of disease-association signals of ancestral risk alleles.     

Anatomical diversity and regressive evolution in trichomanoid filmy ferns (Hymenophyllaceae): a phylogenetic approach

To infer the anatomical evolution of the Hymenophyllaceae (filmy ferns) and to test previously suggested scenarios of regressive evolution, we performed an exhaustive investigation of stem anatomy in the most variable lineage of the family, the trichomanoids, using a representative sampling of 50 species. The evolution of qualitative and quantitative anatomical characters and possibly related growth-forms was analyzed using a maximum likelihood approach. Potential correlations between selected characters were then statistically tested using a phylogenetic comparative method. Our investigations support the anatomical homogeneity of this family at the generic and sub-generic levels. Reduced and sub-collateral/collateral steles likely derived from an ancestral massive protostele, and sub-collateral/collateral types appear to be related to stem thickness reduction and root apparatus regression. These results corroborate the hypothesis of regressive evolution in the lineage, in terms of morphology as well as anatomy. In addition, a heterogeneous cortex, which is derived in the lineage, appears to be related to a colonial strategy and likely to a climbing phenotype. The evolutionary hypotheses proposed in this study lay the ground for further evolutionary analyses that take into account trichomanoid habitats and accurate ecological preferences.     

Ancestral Plasticity and Allometry in Threespine Stickleback Fish Reveal Phenotypes Associated with Derived, Freshwater Ecotypes

For over a century, evolutionary biologists have debated whether and how phenotypic plasticity impacts the processes of adaptation and diversification. The empirical tests required to resolve these issues have proven elusive, mainly because it requires documentation of ancestral reaction norms, a difficult prospect where many ancestors are either extinct or have evolved. The threespine stickleback radiation is not limited in this regard, making it an ideal system in which to address general questions regarding the role of plasticity in adaptive evolution. As retreating ice sheets have exposed new habitats, oceanic stickleback founded innumerable freshwater populations, many of which have evolved parallel adaptations to their new environments. Because the founding oceanic population is extant, we can directly evaluate whether specific patterns of ancestral phenotypic expression in the context of novel environments (plasticity), or over ontogeny, predisposed the repeated evolution of "benthic" and "limnetic" ecotypes in shallow and deep lakes, respectively. Consistent with this hypothesis, we found that oceanic stickleback raised in a complex habitat and fed a macroinvertebrate diet expressed traits resembling derived, benthic fish. Alternatively, when reared in a simple environment on a diet of zooplankton, oceanic stickleback developed phenotypes resembling derived, limnetic fish. As fish in both treatments grew, their body depths increased allometrically, as did the size of their mouths, while their eyes became relatively smaller. Allometric trajectories were subtly but significantly impacted by rearing environment. Thus, both environmental and allometric influences on development, along with their interactive effects, produced variation in phenotypes consistent with derived benthic and limnetic fish, which may have predisposed the repeated genetic accommodation of this specific suite of traits. We also found significant shape differences between marine and anadromous stickleback, which has implications for evaluating the ancestral state of stickleback traits.     

The relative roles of adaptation and phylogeny in determination of larval traits in diversifying anuran lineages

I measured phenotypic traits important to the fitness of larval anurans to assess the relative roles of ancestral trait value and selective regime in determining present-day phenotypes. The positions of 14 species from three taxonomic families and three different habitats in a phenotypic space defined by 19 traits provided measures of taxonomic and ecological similarity. The distribution of phenotypic distances among species revealed that neither taxonomy nor habitat overwhelmingly determined phenotype. There appear to be multiple ways in which anurans can exploit pond types. However, the direction of phenotypic movement was not random from one species to the next. Independent contrasts revealed significant correlations in the evolution of traits that were consistent among lineages. These correlations reflected well-known trade-offs that result from functional relationships among the constituent traits. Although there is no simple pattern in the distribution of mean phenotypes across environments and lineages, the pattern of the evolutionary trajectories that created that distribution is consistent with a predictive theory of multivariate evolution.     

Evolutionary rescue and the coexistence of generalist and specialist competitors: an experimental test

Competition for resources is thought to play a critical role in both the origins and maintenance of biodiversity. Although numerous laboratory evolution experiments have confirmed that competition can be a key driver of adaptive diversification, few have demonstrated its role in the maintenance of the resulting diversity. We investigate the conditions that favour the origin and maintenance of alternative generalist and specialist resource-use phenotypes within the same population. Previously, we confirmed that competition for hosts among φ6 bacteriophage in a mixed novel (non-permissive) and ancestral (permissive) host microcosm triggered the evolution of a generalist phenotype capable of infecting both hosts. However, because the newly evolved generalists tended to competitively exclude the ancestral specialists, coexistence between the two phenotypes was rare. Here, we show that reducing the relative abundance of the novel host slowed the increase in frequency of the generalist phenotype, allowing sufficient time for the specialist to further adapt to the ancestral host. This adaptation resulted in ‘evolutionary rescue’ of the specialists, preventing their competitive exclusion by the generalists. Thus, our results suggest that competition promotes both the origin and maintenance of biodiversity when it is strong enough to favour a novel resource-use phenotype, but weak enough to allow adaptation of both the novel and ancestral phenotypes to their respective niches.     

The existence of species rests on a metastable equilibrium between inbreeding and outbreeding. An essay on the close relationship between speciation, inbreeding and recessive mutations

Background

Speciation corresponds to the progressive establishment of reproductive barriers between groups of individuals derived from an ancestral stock. Since Darwin did not believe that reproductive barriers could be selected for, he proposed that most events of speciation would occur through a process of separation and divergence, and this point of view is still shared by most evolutionary biologists today.

Results

I do, however, contend that, if so much speciation occurs, the most likely explanation is that there must be conditions where reproductive barriers can be directly selected for. In other words, situations where it is advantageous for individuals to reproduce preferentially within a small group and reduce their breeding with the rest of the ancestral population. This leads me to propose a model whereby new species arise not by populations splitting into separate branches, but by small inbreeding groups "budding" from an ancestral stock. This would be driven by several advantages of inbreeding, and mainly by advantageous recessive phenotypes, which could only be retained in the context of inbreeding. Reproductive barriers would thus not arise as secondary consequences of divergent evolution in populations isolated from one another, but under the direct selective pressure of ancestral stocks. Many documented cases of speciation in natural populations appear to fit the model proposed, with more speciation occurring in populations with high inbreeding coefficients, and many recessive characters identified as central to the phenomenon of speciation, with these recessive mutations expected to be surrounded by patterns of limited genomic diversity.

Conclusions

Whilst adaptive evolution would correspond to gains of function that would, most of the time, be dominant, this type of speciation by budding would thus be driven by mutations resulting in the advantageous loss of certain functions since recessive mutations very often correspond to the inactivation of a gene. A very important further advantage of inbreeding is that it reduces the accumulation of recessive mutations in genomes. A consequence of the model proposed is that the existence of species would correspond to a metastable equilibrium between inbreeding and outbreeding, with excessive inbreeding promoting speciation, and excessive outbreeding resulting in irreversible accumulation of recessive mutations that could ultimately only lead to extinction.

Reviewer names

Eugene V. Koonin, Patrick Nosil (nominated by Dr Jerzy Jurka), Pierre Pontarotti     

Estimates of natural selection due to protein tertiary structure inform the ancestry of biallelic loci

We consider the inference of which of two alleles is ancestral when the alleles have a single nonsynonymous difference and when natural selection acts via protein tertiary structure. Whereas the probability that an allele is ancestral under neutrality is equal to its frequency, under selection this probability depends on allele frequency and on the magnitude and direction of selection pressure. Although allele frequencies can be well estimated from intraspecific data, small fitness differences have a large evolutionary impact but can be difficult to estimate with only intraspecific data. Methods for predicting aspects of phenotype from genotype can supplement intraspecific sequence data. Recently developed statistical techniques can assess effects of phenotypes, such as protein tertiary structure on molecular evolution. While these techniques were initially designed for comparing protein-coding genes from different species, the resulting interspecific inferences can be assigned population genetic interpretations to assess the effect of selection pressure, and we use them here along with intraspecific allele frequency data to estimate the probability that an allele is ancestral. We focus on 140 nonsynonymous single nucleotide polymorphisms of humans that are in proteins with known tertiary structures. We find that our technique for employing protein tertiary structure information yields some biologically plausible results but that it does not substantially improve the inference of ancestral human allele types.     

Phylogenetic evidence for horizontal transfer of mutS alleles among naturally occurring Escherichia coli strains

mutS mutators accelerate the bacterial mutation rate 100- to 1,000-fold and relax the barriers that normally restrict homeologous recombination. These mutators thus afford the opportunity for horizontal exchange of DNA between disparate strains. While much is known regarding the mutS phenotype, the evolutionary structure of the mutS(+) gene in Escherichia coli remains unclear. The physical proximity of mutS to an adjacent polymorphic region of the chromosome suggests that this gene itself may be subject to horizontal transfer and recombination events. To test this notion, a phylogenetic approach was employed that compared gene phylogeny to strain phylogeny, making it possible to identify E. coli strains in which mutS alleles have recombined. Comparison of mutS phylogeny against predicted E. coli "whole-chromosome" phylogenies (derived from multilocus enzyme electrophoresis and mdh sequences) revealed striking levels of phylogenetic discordance among mutS alleles and their respective strains. We interpret these incongruences as signatures of horizontal exchange among mutS alleles. Examination of additional sites surrounding mutS also revealed incongruous distributions compared to E. coli strain phylogeny. This suggests that other regional sequences are equally subject to horizontal transfer, supporting the hypothesis that the 61.5-min mutS-rpoS region is a recombinational hot spot within the E. coli chromosome. Furthermore, these data are consistent with a mechanism for stabilizing adaptive changes promoted by mutS mutators through rescue of defective mutS alleles with wild-type sequences.     

Stress‐Induced Evolutionary Innovation: A Mechanism for the Origin of Cell Types

Understanding the evolutionary role of environmentally induced phenotypic variation (i.e., plasticity) is an important issue in developmental evolution. A major physiological response to environmental change is cellular stress, which is counteracted by generic stress reactions detoxifying the cell. A model, stress‐induced evolutionary innovation (SIEI), whereby ancestral stress reactions and their corresponding pathways can be transformed into novel structural components of body plans, such as new cell types, is described. Previous findings suggest that the cell differentiation cascade of a cell type critical to pregnancy in humans, the decidual stromal cell, evolved from a cellular stress reaction. It is hypothesized that the stress reaction in these cells was elicited ancestrally via inflammation caused by embryo attachment. The present study proposes that SIEI is a distinct form of plasticity‐based evolutionary change leading to the origin of novel structures rather than adaptive transformation of pre‐existing characters.     

Environmental change, phenotypic plasticity, and genetic compensation

When a species encounters novel environmental conditions, some phenotypic characters may develop differently than in the ancestral environment. Most environmental perturbations of development are likely to reduce fitness, and thus selection would usually be expected to favor genetic changes that restore the ancestral phenotype. I propose the term "genetic compensation" to refer to this form of adaptive evolution. Genetic compensation is a subset of genetic accommodation and the reverse of genetic assimilation. When genetic compensation has occurred along a spatial environmental gradient, the mean trait values of populations in different environments may be more similar in the field than when representatives of the same populations are raised in a common environment (i.e., countergradient variation). If compensation is complete, genetic divergence between populations may be cryptic, that is, not detectable in the field. Here I apply the concept of genetic compensation to three examples involving carotenoid-based sexual coloration and then use these and other examples to discuss the concept in a broader context. I show that genetic compensation may lead to a cryptic form of reproductive isolation between populations evolving in different environments, may explain some puzzling cases in which heritable traits exposed to strong directional selection fail to show the expected evolutionary response, and may complicate efforts to monitor populations for signs of environmental deterioration.     

Social competition as a driver of phenotype–environment correlations: implications for ecology and evolution

While it is universally recognised that environmental factors can cause phenotypic trait variation via phenotypic plasticity, the extent to which causal processes operate in the reverse direction has received less consideration. In fact individuals are often active agents in determining the environments, and hence the selective regimes, they experience. There are several important mechanisms by which this can occur, including habitat selection and niche construction, that are expected to result in phenotype–environment correlations (i.e. non-random assortment of phenotypes across heterogeneous environments). Here we highlight an additional mechanism – intraspecific competition for preferred environments – that may be widespread, and has implications for phenotypic evolution that are currently underappreciated. Under this mechanism, variation among individuals in traits determining their competitive ability leads to phenotype–environment correlation; more competitive phenotypes are able to acquire better patches. Based on a concise review of the empirical evidence we argue that competition-induced phenotype–environment correlations are likely to be common in natural populations before highlighting the major implications of this for studies of natural selection and microevolution. We focus particularly on two central issues. First, competition-induced phenotype–environment correlation leads to the expectation that positive feedback loops will amplify phenotypic and fitness variation among competing individuals. As a result of being able to acquire a better environment, winners gain more resources and even better phenotypes – at the expense of losers. The distinction between individual quality and environmental quality that is commonly made by researchers in evolutionary ecology thus becomes untenable. Second, if differences among individuals in competitive ability are underpinned by heritable traits, competition results in both genotype–environment correlations and an expectation of indirect genetic effects (IGEs) on resource-dependent life-history traits. Theory tells us that these IGEs will act as (partial) constraints, reducing the amount of genetic variance available to facilitate evolutionary adaptation. Failure to recognise this will lead to systematic overestimation of the adaptive potential of populations. To understand the importance of these issues for ecological and evolutionary processes in natural populations we therefore need to identify and quantify competition-induced phenotype–environment correlations in our study systems. We conclude that both fundamental and applied research will benefit from an improved understanding of when and how social competition causes non-random distribution of phenotypes, and genotypes, across heterogeneous environments.     

A comparative analysis of Wolbachia‐induced host reproductive phenotypes reveals transition rate heterogeneity

The endosymbiotic bacterium Wolbachia infects a wide range of arthropods and their relatives. It is an intracellular parasite transmitted through the egg from mother to offspring. Wolbachia can spread and persist through various means of host reproductive manipulation. How these different mechanisms of host manipulation evolved in Wolbachia is unclear. Which host reproductive phenotype is most likely to be ancestral and whether evolutionary transitions between some host phenotypes are more common than others remain unanswered questions. Recent studies have revealed multiple cases where the same Wolbachia strain can induce different reproductive phenotypes in different hosts, raising the question to what degree the induced host phenotype should be regarded as a trait of Wolbachia. In this study, we constructed a phylogenetic tree of Wolbachia and analyzed the patterns of host phenotypes along that tree. We were able to detect a phylogenetic signal of host phenotypes on the Wolbachia tree, indicating that the induced host phenotype can be regarded as a Wolbachia trait. However, we found no clear support for the previously stated hypothesis that cytoplasmic incompatibility is ancestral to Wolbachia in arthropods. Our analysis provides evidence for heterogeneous transition rates between host phenotypes.     

Sexual tetramorphism in Thymelaea hirsuta (Thymelaeaceae): morph ratios in open-pollinated progeny

Natural populations of Thymelaea hirsuta have previously been shown to comprise four distinct sexual morphs: males, females, protogynous individuals, i.e., first female then male, and protandrous individuals, i.e., first male then female. The objective of the present study has been to confirm the genetic basis of this sexual tetramorphism by quantifying morph ratios in the open-pollinated progeny of the four sexual phenotypes growing in a natural population. All four phenotypes were recovered in the progeny of each morph. All observed plants displayed a single sexual phenotype, thus confirming the genetic basis of the tetramorphism. The progeny sex ratios indicate that the genetic determination of sex in this species may be influenced by cytoplasmic factors, while the observed levels of functional female fertility suggest a near-dioecious system. The evolutionary significance of this tetramorphism as a transitional stage in the evolution of dioecy is discussed.     

Evolution in silico and in vitro: the RNA model.

Theoretical concepts and experiments dealing with the evolution of molecules in vitro reached a state that allows for direct applications to the design of biomolecules with predefined properties. RNA evolution in vitro represents a basis for the development of a new and comprehensive model of evolution, focusing on the phenotype and its fitness relevant properties. Relations between genotypes and phenotypes are described by mappings from genotype space onto a space of phenotypes, which are many-to-one and thus give ample room for neutrality as expressed by the existence of extended neutral networks in genotype space. The RNA model reduces genotype-phenotype relations to mappings from sequences into secondary structures of minimal free energies and allows for derivation of otherwise inaccessible quantitative results. Continuity and discontinuity in evolution are defined through a new notion of accessibility in phenotype space that provides a basis for straight forward interpretation of computer simulations on RNA optimization; furthermore, it reveals the constructive role of random genomic drift in the search for phenotypes of higher fitness. The effects of population size on the course of evolutionary optimization can be predicted quantitatively by means of a simple stochastic model based on a birth-anddeath process with immigration.     

Inferring ancestral sequences in taxon-rich phylogenies

Statistical consistency in phylogenetics has traditionally referred to the accuracy of estimating phylogenetic parameters for a fixed number of species as we increase the number of characters. However, it is also useful to consider a dual type of statistical consistency where we increase the number of species, rather than characters. This raises some basic questions: what can we learn about the evolutionary process as we increase the number of species? In particular, does having more species allow us to infer the ancestral state of characters accurately? This question is particularly important when sequence evolution varies in a complex way from character to character, as methods applicable for i.i.d. models may no longer be valid. In this paper, we assemble a collection of results to analyse various approaches for inferring ancestral information with increasing accuracy as the number of taxa increases.     

生物多样性的熵值结构

多样性一般定义为生物进化过程中物种表现型的丰富程度。从广义上讲,生物进化与环境归类作用的结构复杂性对生物为多样性的解释是很有益处的。我们认为区域水平与样地水平上的气候归类型与植被归类型是最基本的划分因子,本文以中国东北部黑龙江省的山地植被为例,采用多等级熵值分配的方法来证明所使用的方法。我们得出气候归类型与植被归类型所占有的熵值成分要弱于物种表现型丰富度所占有的熵值成份。值得注意的是其相对的熵值贡献率对每一个因子的最大熵值的变化规律。分析结果表明气候归类型占有较低的熵值而植被归类型占有较高的熵值。因此仅仅以在区域气候型为主要指标所划分的物种生态位是不够的,而以小区域内的植被型为指标所产生的物种生态位具有较高利用价值。     

A phylogenetic approach to gene expression data: evidence for the evolutionary origin of mammalian leukocyte phenotypes

SUMMARY The evolution of multicellular organisms involved the evolution of specialized cell types performing distinct functions; and specialized cell types presumably arose from more generalized ancestral cell types as a result of mutational event, such as gene duplication and changes in gene expression. We used characters based on gene expression data to reconstruct evolutionary relationships among 11 types of lymphocytes by the maximum parsimony method. The resulting phylogenetic tree showed expected patterns including separation of the lymphoid and myeloid lineages; clustering together of granulocyte types; and pairing of phenotypically similar cell types such as T-helper cells type 1 and T-helper cells type 2 (Th1 and Th2). We used phylogenetic analyses of sequence data to determine the time of origin of genes showing significant expression difference between Th1 and Th2 cells. Many such genes, particularly those involved in the regulation of gene expression or activation of proteins, were of ancient origin, having arisen by gene duplication before the most recent common ancestor (MRCA) of tetrapods and teleosts. However, certain other genes with significant expression difference between Th1 and Th2 arose after the tetrapod–teleost MRCA, and some of the latter were specific to eutherian (placental) mammals. This evolutionary pattern is consistent with previous evidence that, while bony fishes possess Th1 and Th2 cells, the latter differ phenotypically in important respects from the corresponding cells of mammals. Our results support a gradualistic model of the evolution of distinctive cellular phenotypes whereby the unique characteristics of a given cell type arise as a result of numerous independent mutational changes over hundreds of millions of years.     

Origin and differentiation of Aegilops triuncialis L. as determined by esterase isozyme analysis

Summary Banding patterns of esterase isozymes in Aegilops triuncialis (2n = 28, genome formula C^uC^uCC) and its putative parental species, Ae. umbellulata (2n = 14, C^uC^u) and Ae. caudata (2n = 14, CC), were studied by the gel isoelectric focusing method using pH 6–8 carrier ampholite. Zymogram phenotypes of both parents were quite uniform. Seven zymogram phenotypes (designated as phenotypes 1 to 7) were found among the 260 strains of Ae. triuncialis examined. Of these phenotypes, phenotype 1 was identical to the zymogram phenotype produced by the ancestral species, Ae. umbellulata, and bands considered to have been derived from Ae. caudata were absent in this phenotype. Phenotype 3 had all bands of both parents. The other phenotypes differed greatly from phenotype 3. Therefore, phenotype 3 was considered to be most primitive of the 7 types, and the Ae. triuncialis strains which showed phenotype 3 to be the most primitive of the strains examined. If Ae. triuncialis originated as a hybrid between Ae. umbellulata and Ae. caudata, the zymogram phenotype must have been phenotype 3, in which the isozymes of both parental species are present. Whether the phenotypes other than type 3 were due to introgressive hybridization could not be verified, but they were considered in this article to be a consequence of a rearrangement of chromosomes.Contribution from the Laboratory of Genetics, Faculty of Agriculture, Kyoto University No. 432