Increase In Phenotypic Variance Research Articles

Influence of Hypothyroidism on the Variability of Carotenoid Coloration in Amatitlania nigrofasciata Females (Cichlidae)

The study of the effect of thyroid hormones on the development of the pigment pattern, including the expression of sexual dichromatism, contributes to our understanding of the role of endocrine signaling in the evolution of cichlid fishes, one of the most diverse groups of teleosts. This work shows the effect of reduced thyroid hormone signaling on the development of reversed sexual dichromatism in Amatitlania nigrofasciata, a Neotropical cichlid in which females, unlike males, have carotenoid coloration. In hypothyroid fishes, there was a slowdown in the rate of metamorphic transformations of the pigment pattern and an increase in phenotypic variability. The adult pattern based on carotenoids began to develop in females only after the completion of treatment of thiourea, which suppresses the synthesis of endogenous thyroid hormones. The data obtained indicate a potentially important role of thyroid hormone-mediated developmental plasticity in the diversification of carotenoid coloration in Neotropical cichlids.

Variance components of sex determination in the copepod Tigriopus californicus estimated from a pedigree analysis.

Extensive theory exists regarding population sex ratio evolution that predicts equal sex ratio (when parental investment is equal). In most animals, sex chromosomes determine the sex of offspring, and this fixed genotype for sex has made theory difficult to test since genotypic variance for the trait (sex) is lacking. It has long been argued that the genotype has become fixed in most animals due to the strong selection for equal sex ratios. The marine copepod Tigriopus californicus has no sex chromosomes, multiple genes affecting female brood sex ratio, and a brood sex ratio that responds to selection. The species thus provides an opportune system in which to test established sex ratio theory. In this paper, we further our exploration of polygenic sex determination in T. californicus using an incomplete diallel crossing design for analysis of the variance components of sex determination in the species. Our data confirm the presence of extra-binomial variance for sex, further confirming that sex is not determined through simple Mendelian trait inheritance. In addition, our crosses and backcrosses of isofemale lines selected for biased brood sex ratios show intermediate phenotypic means, as expected if sex is a threshold trait determined by an underlying "liability" trait controlled by many genes of small effects. Furthermore, crosses between families from the same selection line had similar increases in phenotypic variance as crosses between families from different selection lines, suggesting families from artificial selection lines responded to selection pressure through different underlying genetic bases. Finally, we estimate heritability of an individual to be male or female on the observed binary scale as 0.09 (95% CI: 0.034-0.14). This work furthers our accumulating evidence for polygenic sex determination in T. californicus laying the foundation for this as a model species in future studies of sex ratio evolution theory.

Integration of rare expression outlier-associated variants improves polygenic risk prediction

Polygenic risk scores (PRSs) quantify the contribution of multiple genetic loci to an individual's likelihood of a complex trait or disease. However, existing PRSs estimate this likelihood with common genetic variants, excluding the impact of rare variants. Here, we report on a method to identify rare variants associated with outlier gene expression and integrate their impact into PRS predictions for body mass index (BMI), obesity, and bariatric surgery. Between the top and bottom 10%, we observed a 20.8% increase in risk for obesity (p= 3×10-14), 62.3% increase in risk for severe obesity (p= 1×10-6), and median 5.29 years earlier onset for bariatric surgery (p=0.008), as a function of expression outlier-associated rare variant burden when controlling for common variant PRS. We show that these predictions were more significant than integrating the effects of rare protein-truncating variants (PTVs), observing a mean 19% increase in phenotypic variance explained with expression outlier-associated rare variants when compared with PTVs (p= 2×10-15). We replicated these findings by using data from the Million Veteran Program and demonstrated that PRSs across multiple traits and diseases can benefit from the inclusion of expression outlier-associated rare variants identified through population-scale transcriptome sequencing.

Developmental temperature affects phenotypic means and variability: A meta‐analysis of fish data

AbstractFishes are sensitive to their thermal environment and face an uncertain future in a warming world. Theoretically, populations in novel environments might express greater levels of phenotypic variability to increase the chance of surviving—and eventually thriving—in the new conditions. Most research on the effect of the early thermal environment in fish species focuses on average phenotypic effects rather than phenotypic variability, but to understand how fishes will respond to rising temperatures we need to consider both the average response of the population, as well as the breadth of individual responses. Here we present the first meta‐analysis on the effects of developmental temperature in fishes. Using data from 43 species and over 6,000 individual fish, we show that a change in developmental temperature induces a significant change in phenotypic means and variability, but differently depending on whether the temperature is increased or decreased. Decreases in temperature (cool environments) showed a significant decrease in phenotypic means and no change in phenotypic variability. Increases in temperature (warm environments) showed a non‐significant increase in phenotypic means and a marginally significant increase in phenotypic variability. Larger increases in temperature saw greater increases in phenotypic variability, but no increase in the mean phenotypic response. Together, our results suggest that fishes exhibit both directed and stochastic developmental plasticity in response to warming temperatures, which could facilitate or accelerate adaptation to a changing environment.

Maintenance of genetic variation in quantitative traits of a woodland rodent during generations of captive breeding

Breeding programs to conserve diversity are predicated on the assumption that genetic variation in adaptively important traits will be lost in parallel to the loss of variation at neutral loci. To test this assumption, we monitored quantitative traits across 18 generations of Peromyscus leucopus mice propagated with protocols that mirror breeding programs for threatened species. Ears, hind feet, and tails became shorter, but changes were reversible by outcrossing and therefore were due to accumulated inbreeding. Heritability of ear length decreased, because of an increase in phenotypic variance rather than the expected decrease in additive genetic variance. Additive genetic variance in hind foot length increased. This trait initially had low heritability but large dominance or common environmental variance contributing to resemblance among full-sibs. The increase in the additive component indicates that there was conversion of interaction variances to additive variance. For no trait did additive genetic variation decrease significantly across generations. These findings indicate that the restructuring of genetic variance that occurs with genetic drift and novel selection in captivity can prevent or delay the loss of phenotypic and heritable variation, providing variation on which selection can act to adapt populations to captivity and perhaps later to readapt to more natural habitats after release. Therefore, the importance of minimizing loss of gene diversity from conservation breeding programs for threatened wildlife species might lie in preventing immediate reduction in individual fitness due to inbreeding and protecting allelic diversity for long-term evolutionary change, more so than in protecting variation in quantitative traits for rapid re-adaptation to wild environments.

Stochastic loss and gain of symmetric divisions in the C. elegans epidermis perturbs robustness of stem cell number.

Biological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship is to core components of developmental gene networks, and what is the developmental basis of variable phenotypes. Here, we start addressing these questions using the robust number of Caenorhabditis elegans epidermal stem cells, known as seam cells, as a readout. We employ genetics, cell lineage tracing, and single molecule imaging to show that mutations in lin-22, a Hes-related basic helix-loop-helix (bHLH) transcription factor, increase seam cell number variability. We show that the increase in phenotypic variability is due to stochastic conversion of normally symmetric cell divisions to asymmetric and vice versa during development, which affect the terminal seam cell number in opposing directions. We demonstrate that LIN-22 acts within the epidermal gene network to antagonise the Wnt signalling pathway. However, lin-22 mutants exhibit cell-to-cell variability in Wnt pathway activation, which correlates with and may drive phenotypic variability. Our study demonstrates the feasibility to study phenotypic trait variance in tractable model organisms using unbiased mutagenesis screens.

Natural yeast promoter variants reveal epistasis in the generation of transcriptional-mediated noise and its potential benefit in stressful conditions.

The increase in phenotypic variability through gene expression noise is proposed to be an evolutionary strategy in selective environments. Differences in promoter-mediated noise between Saccharomyces cerevisiae strains could have been selected for thanks to the benefit conferred by gene expression heterogeneity in the stressful conditions, for instance, those experienced by industrial strains. Here, we used a genome-wide approach to identify promoters conferring high noise levels in the industrial wine strain EC1118. Many promoters of genes related to environmental factors were identified, some of them containing genetic variations compared with their counterpart in the laboratory strain S288c. Each variant of eight promoters has been fused to yeast-Enhanced Green Fluorescent Protein and integrated in the genome of both strains. Some industrial variants conferred higher expression associated, as expected, with lower noise, but other variants either increased or decreased expression without modifying variability, so that they might exhibit different levels of transcriptional-mediated noise at equal mean. At different induction conditions giving similar expression for both variants of the CUP1 promoter, we indeed observed higher noise with the industrial variant. Nevertheless, this difference was only observed in the industrial strain, revealing epistasis in the generation of promoter-mediated noise. Moreover, the increased expression variability conferred by this natural yeast promoter variant provided a clear benefit in the face of an environmental stress. Thus, modulation of gene expression noise by a combination of promoter modifications and trans-influences might be a possible adaptation mechanism in yeast.

A simulation study of gene-by-environment interactions in GWAS implies ample hidden effects.

The switch to a modern lifestyle in recent decades has coincided with a rapid increase in prevalence of obesity and other diseases. These shifts in prevalence could be explained by the release of genetic susceptibility for disease in the form of gene-by-environment (GxE) interactions. Yet, the detection of interaction effects requires large sample sizes, little replication has been reported, and a few studies have demonstrated environmental effects only after summing the risk of GWAS alleles into genetic risk scores (GRSxE). We performed extensive simulations of a quantitative trait controlled by 2500 causal variants to inspect the feasibility to detect gene-by-environment interactions in the context of GWAS. The simulated individuals were assigned either to an ancestral or a modern setting that alters the phenotype by increasing the effect size by 1.05–2-fold at a varying fraction of perturbed SNPs (from 1 to 20%). We report two main results. First, for a wide range of realistic scenarios, highly significant GRSxE is detected despite the absence of individual genotype GxE evidence at the contributing loci. Second, an increase in phenotypic variance after environmental perturbation reduces the power to discover susceptibility variants by GWAS in mixed cohorts with individuals from both ancestral and modern environments. We conclude that a pervasive presence of gene-by-environment effects can remain hidden even though it contributes to the genetic architecture of complex traits.

The role of founder effects on the evolution of reproductive isolation

Several theories argue that large changes in allele frequencies through genetic drift after a small founding population becomes allopatrically isolated can lead to significant changes in reproductive isolation and thus trigger the origin of new species. For this reason, founder speciation has been proposed as a potent force in the generation of new species. Nonetheless, the relative importance of such 'founder effects' remains largely untested. In this report, I used experimental evolution to create one thousand replicates that underwent an extreme bottleneck and to study whether founder effects can lead to an increase in reproductive isolation in Drosophila yakuba. Even though the most common outcome of inbreeding is extinction, founder effects can lead to increased premating reproductive isolation in a very small proportion of cases. Changes in reproductive isolation after a founding population bottleneck are similar to changes in other phenotypic traits, in which inbreeding might displace the mean phenotypic value and substantially increase the phenotypic variance. This increase in phenotypic variance does not confer an increase in the response to selection for reproductive isolation in artificial selection experiments, indicating that the increased phenotypic variance is not caused by increases in additive genetic variance. These results also demonstrate that, similar to morphological and life-history traits, behavioural traits can be affected by inbreeding and genetic drift.

Effects of post-transcriptional regulation on phenotypic noise in Escherichia coli

Cell-to-cell variations in protein abundance, called noise, give rise to phenotypic variability between isogenic cells. Studies of noise have focused on stochasticity introduced at transcription, yet the effects of post-transcriptional regulatory processes on noise remain unknown. We study the effects of RyhB, a small-RNA of Escherichia coli produced on iron stress, on the phenotypic variability of two of its downregulated target proteins, using dual chromosomal fusions to fluorescent reporters and measurements in live individual cells. The total noise of each of the target proteins is remarkably constant over a wide range of RyhB production rates despite cells being in stress. In fact, coordinate downregulation of the two target proteins by RyhB reduces the correlation between their levels. Hence, an increase in phenotypic variability under stress is achieved by decoupling the expression of different target proteins in the same cell, rather than by an increase in the total noise of each. Extrinsic noise provides the dominant contribution to the total protein noise over the total range of RyhB production rates. Stochastic simulations reproduce qualitatively key features of our observations and show that a feed-forward loop formed by transcriptional extrinsic noise, an sRNA and its target genes exhibits strong noise filtration capabilities.

Whole genome duplication affects evolvability of flowering time in an autotetraploid plant.

Whole genome duplications have occurred recurrently throughout the evolutionary history of eukaryotes. The resulting genetic and phenotypic changes can influence physiological and ecological responses to the environment; however, the impact of genome copy number on evolvability has rarely been examined experimentally. Here, we evaluate the effect of genome duplication on the ability to respond to selection for early flowering time in lines drawn from naturally occurring diploid and autotetraploid populations of the plant Chamerion angustifolium (fireweed). We contrast this with the result of four generations of selection on synthesized neoautotetraploids, whose genic variability is similar to diploids but genome copy number is similar to autotetraploids. In addition, we examine correlated responses to selection in all three groups. Diploid and both extant tetraploid and neoautotetraploid lines responded to selection with significant reductions in time to flowering. Evolvability, measured as realized heritability, was significantly lower in extant tetraploids ( = 0.31) than diploids ( = 0.40). Neotetraploids exhibited the highest evolutionary response ( = 0.55). The rapid shift in flowering time in neotetraploids was associated with an increase in phenotypic variability across generations, but not with change in genome size or phenotypic correlations among traits. Our results suggest that whole genome duplications, without hybridization, may initially alter evolutionary rate, and that the dynamic nature of neoautopolyploids may contribute to the prevalence of polyploidy throughout eukaryotes.

Allelic heterogeneity and more detailed analyses of known loci explain additional phenotypic variation and reveal complex patterns of association

The identification of multiple signals at individual loci could explain additional phenotypic variance (‘missing heritability’) of common traits, and help identify causal genes. We examined gene expression levels as a model trait because of the large number of strong genetic effects acting in cis. Using expression profiles from 613 individuals, we performed genome-wide single nucleotide polymorphism (SNP) analyses to identify cis-expression quantitative trait loci (eQTLs), and conditional analysis to identify second signals. We examined patterns of association when accounting for multiple SNPs at a locus and when including additional SNPs from the 1000 Genomes Project. We identified 1298 cis-eQTLs at an approximate false discovery rate 0.01, of which 118 (9%) showed evidence of a second independent signal. For this subset of 118 traits, accounting for two signals resulted in an average 31% increase in phenotypic variance explained (Wilcoxon P< 0.0001). The association of SNPs with cis gene expression could increase, stay similar or decrease in significance when accounting for linkage disequilibrium with second signals at the same locus. Pairs of SNPs increasing in significance tended to have gene expression increasing alleles on opposite haplotypes, whereas pairs of SNPs decreasing in significance tended to have gene expression increasing alleles on the same haplotypes. Adding data from the 1000 Genomes Project showed that apparently independent signals could be potentially explained by a single association signal. Our results show that accounting for multiple variants at a locus will increase the variance explained in a substantial fraction of loci, but that allelic heterogeneity will be difficult to define without resequencing loci and functional work.

GENOMIC IMPRINTING AND CONFLICT-INDUCED DECANALIZATION

Genomic imprinting is the phenomenon in which the expression pattern of an allele depends on its parental origin. When maternally expressed and paternally expressed imprinted loci affect the same trait, the result is an arms race, with each locus under selection to increase its level of expression. This article develops a model of the deleterious consequences of this escalation, deriving from an increase in the variance in gene expression level, and resulting increase in phenotypic variance in the population. This phenomenon is referred to here as "conflict-induced decanalization." Modifiers that canalize gene expression are selectively favored, but these induce further escalation from both loci, resulting in a net increase in phenotypic variance and a reduction in population mean fitness. This results in a feedback loop, where increasing canalization of gene expression leads to increasing decanalization of the phenotype. This phenomenon may explain the surprisingly high frequency of certain diseases. Disorders to which this decanalization process might contribute include growth- and metabolism-related phenomena such as preterm birth, as well as certain major psychiatric disorders, including schizophrenia and autism.

Fluctuating selection: the perpetual renewal of adaptation in variable environments

Darwin insisted that evolutionary change occurs very slowly over long periods of time, and this gradualist view was accepted by his supporters and incorporated into the infinitesimal model of quantitative genetics developed by R. A. Fisher and others. It dominated the first century of evolutionary biology, but has been challenged in more recent years both by field surveys demonstrating strong selection in natural populations and by quantitative trait loci and genomic studies, indicating that adaptation is often attributable to mutations in a few genes. The prevalence of strong selection seems inconsistent, however, with the high heritability often observed in natural populations, and with the claim that the amount of morphological change in contemporary and fossil lineages is independent of elapsed time. I argue that these discrepancies are resolved by realistic accounts of environmental and evolutionary changes. First, the physical and biotic environment varies on all time-scales, leading to an indefinite increase in environmental variance over time. Secondly, the intensity and direction of natural selection are also likely to fluctuate over time, leading to an indefinite increase in phenotypic variance in any given evolving lineage. Finally, detailed long-term studies of selection in natural populations demonstrate that selection often changes in direction. I conclude that the traditional gradualist scheme of weak selection acting on polygenic variation should be supplemented by the view that adaptation is often based on oligogenic variation exposed to commonplace, strong, fluctuating natural selection.

Canalization and developmental stability in the Brachyrrhine mouse.

The semi-dominant Br mutation affects presphenoid growth, producing the facial retrognathism and globular neurocranial vault that characterize heterozygotes. We analysed the impact of this mutation on skull shape, comparing heterozygotes to wildtype mice, to determine if the effects are skull-wide or confined to the sphenoid region targeted by the mutation. In addition, we examined patterns of variability of shape for the skull as a whole and for three regions (basicranium, face and neurocranium). We found that the Br mice differed significantly from wildtype mice in skull shape in all three regions as well as in the shape of the skull as a whole. However, the significant increases in variance and fluctuating asymmetry were found only in the basicranium of mutant mice. These results suggest that the mutation has a significant effect on the underlying developmental architecture of the skull, which produces an increase in phenotypic variability that is localized to the anatomical region in which the mean phenotype is most dramatically affected. These results suggest that the same developmental mechanisms that produce the change in phenotypic mean also produce the change in variance.

The brachymorph mouse and the developmental‐genetic basis for canalization and morphological integration

Although it is well known that many mutations influence phenotypic variability as well as the mean, the underlying mechanisms for variability effects are very poorly understood. The brachymorph (bm) phenotype results from an autosomal recessive mutation in the phosphoadenosine-phosphosulfate synthetase 2 gene (Papps2). A major cranial manifestation is a dramatic reduction in the growth of the chondrocranium which results from undersulfation of glycosaminoglycans (GAGs) in the cartilage matrix. We found that this reduction in the growth of the chondrocranium is associated with an altered pattern of craniofacial shape variation, a significant increase in phenotypic variance and a dramatic increase in morphological integration for craniofacial shape. Both effects are largest in the basicranium. The altered variation pattern indicates that the mutation produces developmental influences on shape that are not present in the wildtype. As the mutation dramatically reduces sulfation of GAGs, we infer that this influence is variation among individuals in the degree of sulfation, or variable expressivity of the mutation. This variation may be because of genetic variation at other loci that influence sulfation, environmental effects, or intrinsic effects. We infer that chondrocranial development exhibits greater sensitivity to variation in the sulfation of chondroitin sulfate when the degree of sulfation is low. At normal levels, sulfation probably contributes minimally to phenotypic variation. This case illustrates canalization in a particular developmental-genetic context.

Ecological opportunity and levels of morphological variance within freshwater stickleback populations

The ‘ecological opportunity’ hypothesis predicts that when interspecific competition or predation is reduced, populations will exhibit increases in phenotypic variance as a result of colonization and adaptation to vacant or underutilized ecological niches (i.e. character release). We assessed this hypothesis by examining morphological diversity within stickleback populations in 40 undisturbed lakes from six islands off the mid-coast of British Columbia, Canada. Because larger lakes with well-developed littoral and limnetic zones will have greater trophic niche diversity than smaller lakes with only littoral zones, we predicted a positive association between lake size and variation in trophic morphology. Conversely, reduced vertebrate predation in small bog lakes allows increased variance in defensive structures without costs to fitness. Consistent with both predictions, we observed that phenotypic variance in two traits that are involved in feeding (gape width and pectoral fin length) increased with lake size while variability in defence structures (lateral plate number and dorsal spine length) was inversely related to lake size. Moreover, increased variance in defence morphology was accentuated in populations with severe armour reduction (spine loss, decreased plate overlap), another strong indicator of reduced vertebrate predation. In the majority of cases, these patterns were repeatable among islands, independent from the geographical distance between lakes, and arose from a combination of high variance within each of the sexes and increases in sexual dimorphism. These findings suggest that character release can be trait-specific and reflect the combined effects of competition, predation and habitat heterogeneity. © 2005 The Linnean Society of London, Biological Journal of the Linnean Society, 2005, 86, 297–308.

Matrix decomposition model for investigating prehistoric intracemetery biological variation.

A matrix decomposition model for analyzing prehistoric intracemetery biological variability is presented. The model, based on the correlation between interindividual biological and burial distance matrices, provides an estimate of the number of distinct burial populations interred within a single cemetery, which effectively ameliorates identifiability problems typical of general variability analyses (Raemsch [1995] Ph.D. dissertation, SUNY at Albany). Unlike other methods for analyzing intrasite variability analysis (e.g., kinship analysis and microchronology), this method is not reliant on a priori subgroup definition. Assuming a kin-structured burial pattern, a residual matrix is defined based on the raw data matrices; the proportion of negative or zero residuals to the total number of residuals provides an estimate of the number of hidden subgroupings (lineages) within the cemetery. The comparative utility of the model is demonstrated on a series of protohistoric and historic period skeletal samples from the Georgia coast, where it demonstrated that the increase in phenotypic variability during the early mission period is the result of population aggregation at the missions and not necessarily genetic admixture between local and nonlocal groups.

Intraspecific hybridization, developmental stability and fitness in Drosophila mercatorum.

One of the possible effects of intraspecific hybridization is outbreeding depression, due to a breakdown of coadapted gene complexes, which can lead to reduced fitness and decreased developmental stability in hybrids. Alternatively, increased fitness and increased developmental stability in hybrids (hybrid vigour) may be a result of hybridization, probably due to increased heterozygosity. Developmental stability is assumed to be correlated with fitness and is commonly measured as fluctuating asymmetry or phenotypic variance. Drosophila mercatorum is capable of reproducing sexually, but also parthenogenetically in the laboratory. When selecting for parthenogenesis, the flies become homozygous in one generation; strong selection, therefore, is acting on the genome of these flies for coadaptation among genes. Intraspecific hybridization is therefore expected to have an impact when coadaptation is disrupted. Intraspecific hybridization between a parthenogenetic and a sexually reproducing strain of Drosophila mercatorum resulted in significant changes in fecundity as well as fluctuating asymmetry and phenotypic variance for the number of sternopleural bristles and in the length of two wing traits over three generations after hybridization. We found a 'hybrid vigour effect' in Fl females with an increase in fecundity relative to their parental populations. The F2 and F3 females showed increased fluctuating asymmetry in several traits and reduced fecundity compared with the Fl females, probably due to a breakdown in coadapted gene complexes. The males followed the same pattern of fluctuating asymmetry for bristles but there was no increase in wing fluctuating asymmetry in the F2 and F3 generations. Trait differences in phenotypic variance were found between wings and bristles. We found an increase in phenotypic variance in the Fl generation for both sexes and all traits, which could be due to increased genetic variance after hybridization. The phenotypic variance increased further in generations F2 and F3 for bristle number. For the wings, phenotypic variance generally decreased in generations F2 and F3 when compared with Fl, which we attribute to canalization and selection on the wings.

Intraspecific competition favours niche width expansion in Drosophila melanogaster.

Ecologists have proposed that when interspecific competition is reduced, competition within a species becomes a potent evolutionary force leading to rapid diversification. This view reflects the observation that populations invading species-poor communities frequently evolve broader niches. Niche expansion can be associated with an increase in phenotypic variance (known as character release), with the evolution of polymorphisms, or with divergence into many species using distinct resources (adaptive radiation). The relationship between intraspecific competition and diversification is known from theory, and has been used as the foundation for some models of speciation. However, there has been little empirical proof that niches evolve in response to intraspecific competition. To test this hypothesis, I introduced cadmium-intolerant Drosophila melanogaster populations to environments containing both cadmium-free and cadmium-laced resources. Here I show that populations experiencing high competition adapted to cadmium more rapidly than low competition populations. This provides experimental confirmation that competition in a population can drive niche expansion onto new resources for which competition is less severe.