Cascading indirect genetic effects in a clonal vertebrate.

Understanding how individual differences arise and how their effects propagate through groups are fundamental issues in biology. Individual differences can arise from indirect genetic effects (IGE): genetically based variation in the conspecifics with which an individual interacts. Using a clonal species, the Amazon molly (Poecilia formosa), we test the hypothesis that IGE can propagate to influence phenotypes of the individuals that do not experience them firsthand. We tested this by exposing genetically identical Amazon mollies to conspecific social partners of different clonal lineages, and then moving these focal individuals to new social groups in which they were the only member to have experienced the IGE. We found that genetically different social environments resulted in the focal animals experiencing different levels of aggression, and that these IGE carried over into new social groups to influence the behaviour of naive individuals. These data reveal that IGE can cascade beyond the individuals that experience them. Opportunity for cascading IGE is ubiquitous, especially in species with long-distance dispersal or fission-fusion group dynamics. Cascades could amplify (or mitigate) the effects of IGE on trait variation and on evolutionary trajectories. Expansion of the IGE framework to include cascading and other types of carry-over effects will therefore improve understanding of individual variation and social evolution and allow more accurate prediction of population response to changing environments.

On the genetic architecture of rapidly adapting and convergent life history traits in guppies.

The genetic basis of traits shapes and constrains how adaptation proceeds in nature; rapid adaptation can proceed using stores of polygenic standing genetic variation or hard selective sweeps, and increasing polygenicity fuels genetic redundancy, reducing gene re-use (genetic convergence). Guppy life history traits evolve rapidly and convergently among natural high- and low-predation environments in northern Trinidad. This system has been studied extensively at the phenotypic level, but little is known about the underlying genetic architecture. Here, we use four independent F2 QTL crosses to examine the genetic basis of seven (five female, two male) guppy life history phenotypes and discuss how these genetic architectures may facilitate or constrain rapid adaptation and convergence. We use RAD-sequencing data (16,539 SNPs) from 370 male and 267 female F2 individuals. We perform linkage mapping, estimates of genome-wide and per-chromosome heritability (multi-locus associations), and QTL mapping (single-locus associations). Our results are consistent with architectures of many loci of small-effect for male age and size at maturity and female interbrood period. Male trait associations are clustered on specific chromosomes, but female interbrood period exhibits a weak genome-wide signal suggesting a potentially highly polygenic component. Offspring weight and female size at maturity are also associated with a single significant QTL each. These results suggest rapid, repeatable phenotypic evolution of guppies may be facilitated by polygenic trait architectures, but subsequent genetic redundancy may limit gene re-use across populations, in agreement with an absence of strong signatures of genetic convergence from recent analyses of wild guppies.

A large and diverse autosomal haplotype is associated with sex-linked colour polymorphism in the guppy.

Male colour patterns of the Trinidadian guppy (Poecilia reticulata) are typified by extreme variation governed by both natural and sexual selection. Since guppy colour patterns are often inherited faithfully from fathers to sons, it has been hypothesised that many of the colour trait genes must be physically linked to sex determining loci as a 'supergene' on the sex chromosome. Here, we phenotype and genotype four guppy 'Iso-Y lines', where colour was inherited along the patriline for 40 generations. Using an unbiased phenotyping method, we confirm the breeding design was successful in creating four distinct colour patterns. We find that genetic differentiation among the Iso-Y lines is repeatedly associated with a diverse haplotype on an autosome (LG1), not the sex chromosome (LG12). Moreover, the LG1 haplotype exhibits elevated linkage disequilibrium and evidence of sex-specific diversity in the natural source population. We hypothesise that colour pattern polymorphism is driven by Y-autosome epistasis.

Indirect Genetic Effects: A Cross-disciplinary Perspective on Empirical Studies.

Indirect genetic effects (IGE) occur when an individual's phenotype is influenced by genetic variation in conspecifics. Opportunities for IGE are ubiquitous, and, when present, IGE have profound implications for behavioral, evolutionary, agricultural, and biomedical genetics. Despite their importance, the empirical study of IGE lags behind the development of theory. In large part, this lag can be attributed to the fact that measuring IGE, and deconvoluting them from the direct genetic effects of an individual's own genotype, is subject to many potential pitfalls. In this Perspective, we describe current challenges that empiricists across all disciplines will encounter in measuring and understanding IGE. Using ideas and examples spanning evolutionary, agricultural, and biomedical genetics, we also describe potential solutions to these challenges, focusing on opportunities provided by recent advances in genomic, monitoring, and phenotyping technologies. We hope that this cross-disciplinary assessment will advance the goal of understanding the pervasive effects of conspecific interactions in biology.

Using Delaunay triangulation to sample whole-specimen color from digital images.

Color variation is one of the most obvious examples of variation in nature, but biologically meaningful quantification and interpretation of variation in color and complex patterns are challenging. Many current methods for assessing variation in color patterns classify color patterns using categorical measures and provide aggregate measures that ignore spatial pattern, or both, losing potentially important aspects of color pattern.Here, we present Colormesh, a novel method for analyzing complex color patterns that offers unique capabilities. Our approach is based on unsupervised color quantification combined with geometric morphometrics to identify regions of putative spatial homology across samples, from histology sections to whole organisms. Colormesh quantifies color at individual sampling points across the whole sample.We demonstrate the utility of Colormesh using digital images of Trinidadian guppies (Poecilia reticulata), for which the evolution of color has been frequently studied. Guppies have repeatedly evolved in response to ecological differences between up- and downstream locations in Trinidadian rivers, resulting in extensive parallel evolution of many phenotypes. Previous studies have, for example, compared the area and quantity of discrete color (e.g., area of orange, number of black spots) between these up- and downstream locations neglecting spatial placement of these areas. Using the Colormesh pipeline, we show that patterns of whole-animal color variation do not match expectations suggested by previous work.Colormesh can be deployed to address a much wider range of questions about color pattern variation than previous approaches. Colormesh is thus especially suited for analyses that seek to identify the biologically important aspects of color pattern when there are multiple competing hypotheses or even no a priori hypotheses at all.

Can You Trust Who You See? The Evolution of Socially Cued Anticipatory Plasticity.

AbstractThe social environment can affect development and fitness. However, we do not know how selection acts on individuals that cue developmental pathways using features of the social environment. Socially cued anticipatory plasticity (SCAP) is a hypothetical strategy whereby juveniles use social cues to alter development to match their adult phenotype to the social environment that they expect to encounter. While intuitively appealing, the evolution of such plasticity is a puzzle, because the cue changes when individuals use it. Can socially cued plasticity evolve when such a feedback occurs? We use individual-based simulations to model evolution of SCAP in an environment that fluctuates between favoring each of two discrete phenotypes. We found that socially cued plasticity evolved, but only when strong selection acted on survival rather than on fecundity differences between adult phenotypes. In this case, the social cue reliably predicted which phenotype would be favored on maturation. Surprisingly, costs to plasticity increased the range of conditions under which it was adaptive. In the absence of costs, evolution led to a state where SCAP individuals could not effectively respond to environmental changes. Costs to plasticity lowered the proportion of the population that used SCAP, which in turn increased the reliability of the social cue and allowed individuals that used socially cued plasticity to switch between the favored phenotypes more consistently. Our results suggest that the evolution of adaptive plasticity in response to social cues may represent a larger class of problems in which evolution is hard to predict because of feedbacks among critical processes.

Paternal exposure to a common pharmaceutical (Ritalin) has transgenerational effects on the behaviour of Trinidadian guppies.

Evidence is emerging that paternal effects, the nongenetic influence of fathers on their offspring, can be transgenerational, spanning several generations. Methylphenidate hydrochloride (MPH; e.g. Ritalin) is a dopaminergic drug that is highly prescribed to adolescent males for the treatment of Attention-deficit/hyperactivity disorder. It has been suggested that MPH could cause transgenerational effects because MPH can affect the male germline in rodents and because paternal effects have been observed in individuals taking similar drugs (e.g. cocaine). Despite these concerns, the transgenerational effects of paternal MPH exposure are unknown. Therefore, we exposed male and female Trinidadian guppies (Poecilia reticulata) to a low, chronic dose of MPH and observed that MPH affected the anxiety/exploratory behaviour of males, but not females. Because of this male-specific effect, we investigated the transgenerational effects of MPH through the paternal line. We observed behavioural effects of paternal MPH exposure on offspring and great-grandoffspring that were not directly administered the drug, making this the first study to demonstrate that paternal MPH exposure can affect descendants. These effects were not due to differential mortality or fecundity between control and MPH lines. These results highlight the transgenerational potential of MPH.

Nonparallel transcriptional divergence during parallel adaptation.

How underlying mechanisms bias evolution toward predictable outcomes remains an area of active debate. In this study, we leveraged phenotypic plasticity and parallel adaptation across independent lineages of Trinidadian guppies (Poecilia reticulata) to assess the predictability of gene expression evolution during parallel adaptation. Trinidadian guppies have repeatedly and independently adapted to high- and low-predation environments in the wild. We combined this natural experiment with a laboratory breeding design to attribute transcriptional variation to the genetic influences of population of origin and developmental plasticity in response to rearing with or without predators. We observed substantial gene expression plasticity, as well as the evolution of expression plasticity itself, across populations. Genes exhibiting expression plasticity within populations were more likely to also differ in expression between populations, with the direction of population differences more likely to be opposite those of plasticity. While we found more overlap than expected by chance in genes differentially expressed between high- and low-predation populations from distinct evolutionary lineages, the majority of differentially expressed genes were not shared between lineages. Our data suggest alternative transcriptional configurations associated with shared phenotypes, highlighting a role for transcriptional flexibility in the parallel phenotypic evolution of a species known for rapid adaptation.

Sex differences in the plasticity of life history in response to social environment.

Predicting how social environment affects life history variation is critical to understanding if, and when, selection favors alternative life history development, especially in systems in which social interactions change over time or space. Although sexual selection theory predicts that males and females should respond differently to variation in the social environment, few studies have examined the responses of both male and female phenotypes to the same gradient of social environment. In this study, we used a livebearing fish to determine how males and females altered their life histories in response to variation in the social environment during development. We found that both males and females delayed maturity and attained larger sizes when their social environment included adults, in contrast to developing in juvenile-only environments. The magnitude of this effect differed substantially between the sexes. The common pattern of response in the sexes suggested that life history trade-offs, rather than sexual selection, is responsible for these changes in life history expression. These effects make the relationship between genotype and phenotype depend strongly on the environment experienced by each individual. These results indicate that social environment is an important driver of life history variation in sailfin mollies and can be at least as important as abiotic effects.

Mating Preference for Novel Phenotypes Can Be Explained by General Neophilia in Female Guppies.

AbstractUnderstanding how genetic variation is maintained in ecologically important traits is a fundamental question in evolutionary biology. Male Trinidadian guppies (Poecilia reticulata) exhibit extreme genetic diversity in color patterns within populations, which is believed to be promoted by a female mating preference for rare or novel patterns. However, the origins of this preference remain unclear. Here, we test the hypothesis that mating preference for novel phenotypes is a by-product of general neophilia that evolved in response to selection in nonmating contexts. We measured among-female variation in preference for eight different, novel stimuli that spanned four ecological contexts: mate choice, exploration, foraging, and social (but nonsexual) interactions. Females exhibited preference for novelty in six out of eight tests. Individual variation in preference for novelty was positively correlated among all eight types of stimuli. Furthermore, factor analysis revealed a single axis of general neophilia that accounts for 61% of individual variation in preference for novel color patterns. The single-factor structure of neophilia suggests that interest in novelty is governed primarily by shared processes that transcend context. Because neophilia likely has a sizable heritable component, our results provide evidence that mating preference for novel phenotypes may be a nonadaptive by-product of natural selection on neophilia.

Pervasive Linked Selection and Intermediate-Frequency Alleles Are Implicated in an Evolve-and-Resequencing Experiment of Drosophila simulans.

We develop analytical and simulation tools for evolve-and-resequencing experiments and apply them to a new study of rapid evolution in Drosophila simulans Likelihood test statistics applied to pooled population sequencing data suggest parallel evolution of 138 SNPs across the genome. This number is reduced by orders of magnitude from previous studies (thousands or tens of thousands), owing to differences in both experimental design and statistical analysis. Whole genome simulations calibrated from Drosophila genetic data sets indicate that major features of the genome-wide response could be explained by as few as 30 loci under strong directional selection with a corresponding hitchhiking effect. Smaller effect loci are likely also responding, but are below the detection limit of the experiment. Finally, SNPs showing strong parallel evolution in the experiment are intermediate in frequency in the natural population (usually 30-70%) indicative of balancing selection in nature. These loci also exhibit elevated differentiation among natural populations of D. simulans, suggesting environmental heterogeneity as a potential balancing mechanism.

Why does the magnitude of genotype-by-environment interaction vary?

Genotype-by-environment interaction (G × E), that is, genetic variation in phenotypic plasticity, is a central concept in ecology and evolutionary biology. G×E has wide-ranging implications for trait development and for understanding how organisms will respond to environmental change. Although G × E has been extensively documented, its presence and magnitude vary dramatically across populations and traits. Despite this, we still know little about why G × E is so evident in some traits and populations, but minimal or absent in others. To encourage synthetic research in this area, we review diverse hypotheses for the underlying biological causes of variation in G × E. We extract common themes from these hypotheses to develop a more synthetic understanding of variation in G × E and suggest some important next steps.

GxG epistasis in growth and condition and the maintenance of genetic polymorphism in Gambusia holbrooki.

Theory on indirect genetic effects (IGEs) indicates that variation in the genetic composition of social groups can generate GxG epistasis that may promote the evolution of stable polymorphisms. Using a livebearing fish with a genetic polymorphism in coloration and associated behavioral differences, we tested whether genotypes of social partners interacted with focal individual genotypes to influence growth and condition over 16 weeks of development. We found that IGEs had a significant influence on patterns of feeding, regardless of focal fish genotype. There was no influence of social environment on juvenile length, but there was significant GxG epistasis for body condition. Each focal juvenile was in better condition when its own genotype was not present in adult social partners. These data are consistent with negative frequency-dependent selection in which each morph performs better when it is rare. Neither variation in feeding nor activity-related behaviors explained variation in body condition, suggesting that GxG epistasis for condition was caused by physiological differences between the two genotypes. These findings indicate that GxG epistasis in a given polymorphism can generate fitness landscapes that contribute to the maintenance of that polymorphism and to maintenance of genetic variation for additional fitness-related traits.

Erratum: Non-adaptive plasticity potentiates rapid adaptive evolution of gene expression in nature.

This corrects the article DOI: 10.1038/nature15256.

Advancing behavioural genomics by considering timescale.

Animal behavioural traits often covary with gene expression, pointing towards a genomic constraint on organismal responses to environmental cues. This pattern highlights a gap in our understanding of the time course of environmentally responsive gene expression, and moreover, how these dynamics are regulated. Advances in behavioural genomics explore how gene expression dynamics are correlated with behavioural traits that range from stable to highly labile. We consider the idea that certain genomic regulatory mechanisms may predict the timescale of an environmental effect on behaviour. This temporally minded approach could inform both organismal and evolutionary questions ranging from the remediation of early life social trauma to understanding the evolution of trait plasticity.

Pleiotropy, constraint, and modularity in the evolution of life histories: insights from genomic analyses.

Multicellular organisms display an enormous range of life history (LH) strategies and present an evolutionary conundrum; despite strong natural selection, LH traits are characterized by high levels of genetic variation. To understand the evolution of life histories and maintenance of this variation, the specific phenotypic effects of segregating alleles and the genetic networks in which they act need to be elucidated. In particular, the extent to which LH evolution is constrained by the pleiotropy of alleles contributing to LH variation is generally unknown. Here, we review recent empirical results that shed light on this question, with an emphasis on studies employing genomic analyses. While genome-scale analyses are increasingly practical and affordable, they face limitations of genetic resolution and statistical power. We describe new research approaches that we believe can produce new insights and evaluate their promise and applicability to different kinds of organisms. Two approaches seem particularly promising: experiments that manipulate selection in multiple dimensions and measure phenotypic and genomic response and analytical approaches that take into account genome-wide associations between markers and phenotypes, rather than applying a traditional marker-by-marker approach.

Stimulation of the Drosophila immune system alters genome-wide nucleosome occupancy.

In eukaryotes, nucleosomes participate in all DNA-templated events by regulating access to the underlying DNA sequence. However, nucleosome dynamics during a genome response have not been well characterized [1,2]. We stimulated Drosophila S2 cells with heat-killed Gram-negative bacteria Salmonella typhimurium, and mapped genome-wide nucleosome occupancy at high temporal resolution by MNase-seq using Illumina HiSeq 2500. We show widespread nucleosome occupancy change in S2 cells during the immune response, with the significant nucleosomal loss occurring at 4 h after stimulation. Data have been deposited to the Gene Expression Omnibus (GEO) database repository with the dataset identifier GSE64507.

Non-adaptive plasticity potentiates rapid adaptive evolution of gene expression in nature.

Phenotypic plasticity is the capacity for an individual genotype to produce different phenotypes in response to environmental variation. Most traits are plastic, but the degree to which plasticity is adaptive or non-adaptive depends on whether environmentally induced phenotypes are closer or further away from the local optimum. Existing theories make conflicting predictions about whether plasticity constrains or facilitates adaptive evolution. Debate persists because few empirical studies have tested the relationship between initial plasticity and subsequent adaptive evolution in natural populations. Here we show that the direction of plasticity in gene expression is generally opposite to the direction of adaptive evolution. We experimentally transplanted Trinidadian guppies (Poecilia reticulata) adapted to living with cichlid predators to cichlid-free streams, and tested for evolutionary divergence in brain gene expression patterns after three to four generations. We find 135 transcripts that evolved parallel changes in expression within the replicated introduction populations. These changes are in the same direction exhibited in a native cichlid-free population, suggesting rapid adaptive evolution. We find 89% of these transcripts exhibited non-adaptive plastic changes in expression when the source population was reared in the absence of predators, as they are in the opposite direction to the evolved changes. By contrast, the remaining transcripts exhibiting adaptive plasticity show reduced population divergence. Furthermore, the most plastic transcripts in the source population evolved reduced plasticity in the introduction populations, suggesting strong selection against non-adaptive plasticity. These results support models predicting that adaptive plasticity constrains evolution, whereas non-adaptive plasticity potentiates evolution by increasing the strength of directional selection. The role of non-adaptive plasticity in evolution has received relatively little attention; however, our results suggest that it may be an important mechanism that predicts evolutionary responses to new environments.

Vitellogenin family gene expression does not increase Drosophila lifespan or fecundity.

One of the most striking patterns in comparative biology is the negative correlation between lifespan and fecundity observed in comparisons among species. This pattern is consistent with the idea that organisms need to allocate a fixed energy budget among competing demands of growth, development, reproduction and somatic maintenance. However, exceptions to this pattern have been observed in many social insects, including ants, bees, and termites.  In honey bees ( Apis mellifera), Vitellogenin ( Vg), a yolk protein precursor, has been implicated in mediating the long lifespan and high fecundity of queen bees. To determine if Vg-like proteins can regulate lifespan in insects generally, we examined the effects of expression of Apis Vg and Drosophila CG31150 (a Vg-like gene recently identified as cv-d) on Drosophila melanogaster lifespan and fecundity using the RU486-inducible GeneSwitch system. For all genotypes tested, overexpression of Vg and CG31150 decreased Drosophila lifespan and did not affect total or age-specific fecundity. We also detected an apparent effect of the GeneSwitch system itself, wherein RU486 exposure (or the GAL4 expression it induces) led to a significant increase in longevity and decrease in fecundity in our fly strains. This result is consistent with the pattern reported in a recent meta-analysis of Drosophila aging studies, where transgenic constructs of the UAS/GAL4 expression system that should have no effect (e.g. an uninduced GeneSwitch) significantly extended lifespan in some genetic backgrounds. Our results suggest that Vg-family genes are not major regulators of Drosophila life history traits, and highlight the importance of using appropriate controls in aging studies.