Phenotypic Variation In Natural Populations Research Articles

Diallel panel reveals a significant impact of low-frequency genetic variants on gene expression variation in yeast.

Unraveling the genetic sources of gene expression variation is essential to better understand the origins of phenotypic diversity in natural populations. Genome-wide association studies identified thousands of variants involved in gene expression variation, however, variants detected only explain part of the heritability. In fact, variants such as low-frequency and structural variants (SVs) are poorly captured in association studies. To assess the impact of these variants on gene expression variation, we explored a half-diallel panel composed of 323 hybrids originated from pairwise crosses of 26 natural Saccharomyces cerevisiae isolates. Using short- and long-read sequencing strategies, we established an exhaustive catalog of single nucleotide polymorphisms (SNPs) and SVs for this panel. Combining this dataset with the transcriptomes of all hybrids, we comprehensively mapped SNPs and SVs associated with gene expression variation. While SVs impact gene expression variation, SNPs exhibit a higher effect size with an overrepresentation of low-frequency variants compared to common ones. These results reinforce the importance of dissecting the heritability of complex traits with a comprehensive catalog of genetic variants at the population level.

Developmental stress does not induce genome-wide DNA methylation changes in wild great tit (Parus major) nestlings.

The environment experienced during early life is a crucial factor in the life of many organisms. This early life environment has been shown to have profound effects on morphology, physiology and fitness. However, the molecular mechanisms that mediate these effects are largely unknown, even though they are essential for our understanding of the processes that induce phenotypic variation in natural populations. DNA methylation is an epigenetic mechanism that has been suggested to explain such environmentally induced phenotypic changes early in life. To investigate whether DNA methylation changes are associated with experimentally induced early developmental effects, we cross-fostered great tit (Parus major) nestlings and manipulated their brood sizes in a natural study population. We assessed experimental brood size effects on pre-fledging biometry and behaviour. We linked this to genome-wide DNA methylation levels of CpG sites in erythrocyte DNA, using 122 individuals and an improved epiGBS2 laboratory protocol. Brood enlargement caused developmental stress and negatively affected nestling condition, predominantly during the second half of the breeding season, when conditions are harsher. Brood enlargement, however, affected nestling DNA methylation in only one CpG site and only if the hatch date was taken into account. In conclusion, this study shows that nutritional stress in enlarged broods does not associate with direct effects on genome-wide DNA methylation. Future studies should assess whether genome-wide DNA methylation variation may arise later in life as a consequence of phenotypic changes during early development.

Mapping splice QTLs reveals distinct transcriptional and post-transcriptional regulatory variation of gene expression and identifies putative alternative splicing variation mediating complex trait variation in pigs

BackgroundAlternative splicing is an important step in gene expression, generating multiple isoforms for the same genes and greatly expanding the diversity of proteomes. Genetic variation in alternative splicing contributes to phenotypic diversity in natural populations. However, the genetic basis of variation in alternative splicing in livestock including pigs remains poorly understood.ResultsIn this study, using a Duroc x Pietrain F2 pig population, we performed genome-wide analysis of alternative splicing estimated from stranded RNA-Seq data in skeletal muscle. We characterized the genetic architecture of alternative splicing and compared its basic features with those of overall gene expression. We detected a large number of novel alternative splicing events that were not previously annotated. We found heritability of quantitative alternative splicing scores (percent spliced in or PSI) to be lower than that of overall gene expression. In addition, heritabilities showed little correlation between alternative splicing and overall gene expression. We mapped expression QTLs (eQTLs) and splice QTLs (sQTLs) and found them to be largely non-overlapping. Finally, we integrated sQTL mapping with phenotype QTL (pQTL mapping to identify potential mediator of pQTL effect by alternative splicing.ConclusionsOur results suggest that regulatory variation exists at multiple levels and that their genetic controls are distinct, offering opportunities for genetic improvement.

Leaf phenotypic variation in natural populations of Carpinus tschonoskii in China

Leaf phenotypic variation in natural populations of Carpinus tschonoskii in China

Leaf phenotypic variation in natural populations of <i>Quillaja saponaria</i> and its relationship with climatic variation

Quillaja saponaria is a sclerophyllus evergreen tree species distributed from 30° to 38° S in Central Chile. In this wide distribution it is expected that the species exhibits phenotypic plasticity in the morphology of leaves associated to climate variation; however, the information on this topic is still scarce. We studied leaf phenotypic variation and its relationship with temperature, precipitation, and aridity in 85 stands of Q. saponaria throughout the natural distribution of the species. The results show that the basal diameter of petiole, the number of secondary veins, and the basal diameter of the principal vein increased with precipitation and decreased with aridity, while the length, basal diameter and the relative length of the petiole decreased with temperature. This confirms that phenotypic variation for foliar characters in Q. saponaria is related to climatic variables indicating an adapting capability of the species to the wide range of environmental conditions in which grows.

A comparative study of natural variation in hemolymph glucose levels under different dietary sugar conditions in Drosophila melanogaster and D. simulans.

Physiological responses to environmental changes play important roles in adaptive evolution. In particular, homeostatic regulatory systems that maintain constant circulating glucose levels are crucial in animals. However, variation in circulating glucose levels and the genetic effects on phenotypic variation in natural populations remain to be clarified. Here, we investigated the hemolymph glucose levels in natural populations of Drosophila melanogaster and its sibling species, D. simulans, in Japan. We quantified hemolymph glucose concentrations in third instar larvae of 27 lines for each species, which were reared on either glucose-free or glucose-rich food. In both species, genetic variation was not a major component of phenotypic variation on either glucose-free or glucose-rich food. The hemolymph glucose concentrations were much higher in D. simulans than in D. melanogaster. Genetic variance was larger in D. simulans than in D. melanogaster. The observed differences between the two species may be associated with the much more recent colonization history of D. simulans populations in Japan and/or the tolerance to environmental stresses. Our findings suggest that natural selection acting on hemolymph glucose levels in D. melanogaster is different from that in D. simulans.

The phenotypic diversity of Schisandra sphenanthera fruit and SVR model for phenotype forecasting

Schisandra sphenanthera Rehd. et Wils. is an endangered traditional Chinese medical plant whose fruits can be used for medicinal purposes, and is mainly distributed in the Qinling Mountains. Presently, little is known about the phenotypic diversity in natural populations of S. sphenanthera, and its fitness and evolutionary potential to the environmental factors, which is important for its conservation. In this study, we have made an in-depth research of the degree of phenotypic differentiation between and within populations, phenotypic diversity, environment factors on phenotypic differentiation, and the prediction of fruit phenotypes under different environments. The phenotypic diversity of S. sphenanthera fruits on a large scale (9 provinces, 25 counties) is evaluated by means of cluster analysis, principle component analysis, statistics of phenotypic traits diversity index and differentiation coefficient. Our data report a high degree of variation between the 25 populations for most morphological traits. The average phenotypic variation between populations accounts for 27.11%, and the average phenotypic variation within populations accounts for 72.89%. 25 populations are divided into four categories based on twelve fruit phenotypic traits of S. sphenanthera. Five counties in Shaanxi Province are grouped together (cluster I) where the highest single fruit weight and 100-berries fresh weight, which are most closely related to fruit weight. Correlation analysis is used to evaluate the relationship between environmental factors and fruit phenotypes, and path analysis is used to analyse the effect of environmental factors on fruit phenotypes. There are many significant correlations between phenotype and environmental factors. Some factors have direct effects on phenotype, while others are indirect effect factors, for example, bio1 has direct effects on longitudinal and horizontal diameter of fruit and 100-berries weight (including fresh and dry weight), and has indirect effect on fruit pedicels length. Topographic and soil factors mainly affect phenotypes about fruit weight, and phenotypes of fruit shape are affected by topographic and climate factors. Our study propose a data-driven machine learning (ML) method, namely support vector regression (SVR), based on the results of path analysis, which can predict the phenotype of S. sphenanthera in different environments with high prediction accuracy. S. sphenanthera in five counties of Shaanxi Province (cluster I) can serve as an important source of genetic material for wild upbringing towards the development of new breed with high yield in this Chinese herb. This study also finds the environmental factors have significant effect on fruit weight-related phenotypes. The results of this study can provide data support for artificial cultivation to improve fruit yield.

Wild epigenetics: insights from epigenetic studies on natural populations

Epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNAs are increasingly targeted in studies of natural populations. Here, I review some of the insights gained from this research, examine some of the methods currently in use and discuss some of the challenges that researchers working on natural populations are likely to face when probing epigenetic mechanisms. While studies supporting the involvement of epigenetic mechanisms in generating phenotypic variation in natural populations are amassing, many of these studies are currently correlative in nature. Thus, while empirical data point to widespread contributions of epigenetic mechanisms in generating phenotypic variation, there are still concerns as to whether epigenetic variation is instead ultimately controlled by genetic variation. Disentangling these two sources of variation will be a key to resolving the debate about the importance of epigenetic mechanisms, and studies on natural populations that partition the relative contribution of genetic and epigenetic factors to phenotypic variation can play an important role in this debate.

Assessment of the phenotypic diversity in natural populations of Annona coriacea Mart.: implications for breeding

Assessment of the phenotypic diversity in natural populations of Annona coriacea Mart.: implications for breeding

Sexual Antagonism, Temporally Fluctuating Selection, and Variable Dominance Affect a Regulatory Polymorphism in Drosophila melanogaster.

Understanding how genetic variation is maintained within species is a major goal of evolutionary genetics that can shed light on the preservation of biodiversity. Here, we examined the maintenance of a regulatory single-nucleotide polymorphism (SNP) of the X-linked Drosophila melanogaster gene fezzik. The derived variant at this site is at intermediate frequency in many worldwide populations but absent in populations from the ancestral species range in sub-Saharan Africa. We collected and genotyped wild-caught individuals from a single European population biannually over a period of 5 years, which revealed an overall difference in allele frequency between the sexes and a consistent change in allele frequency across seasons in females but not in males. Modeling based on the observed allele and genotype frequencies suggested that both sexually antagonistic and temporally fluctuating selection may help maintain variation at this site. The derived variant is predicted to be female-beneficial and mostly recessive; however, there was uncertainty surrounding our dominance estimates and long-term modeling projections suggest that it is more likely to be dominant. By examining gene expression phenotypes, we found that phenotypic dominance was variable and dependent upon developmental stage and genetic background, suggesting that dominance may be variable at this locus. We further determined that fezzik expression and genotype are associated with starvation resistance in a sex-dependent manner, suggesting a potential phenotypic target of selection. By characterizing the mechanisms of selection acting on this SNP, our results improve our understanding of how selection maintains genetic and phenotypic variation in natural populations.

Genetic and plastic rewiring of food webs under climate change

Climate change is altering ecological and evolutionary processes across biological scales. These simultaneous effects of climate change pose a major challenge for predicting the future state of populations, communities and ecosystems. This challenge is further exacerbated by the current lack of integration of research focused on these different scales.We propose that integrating the fields of quantitative genetics and food web ecology will reveal new insights on how climate change may reorganize biodiversity across levels of organization. This is because quantitative genetics links the genotypes of individuals to population‐level phenotypic variation due to genetic (G), environmental (E) and gene‐by‐environment (G × E) factors. Food web ecology, on the other hand, links population‐level phenotypes to the structure and dynamics of communities and ecosystems.We synthesize data and theory across these fields and find evidence that genetic (G) and plastic (E and G × E) phenotypic variation within populations will change in magnitude under new climates in predictable ways. We then show how changes in these sources of phenotypic variation can rewire food webs by altering the number and strength of species interactions, with consequences for ecosystem resilience. We also find evidence suggesting there are predictable asymmetries in genetic and plastic trait variation across trophic levels, which set the pace for phenotypic change and food web responses to climate change. Advances in genomics now make it possible to partition G, E and G × E phenotypic variation in natural populations, allowing tests of the hypotheses we propose.By synthesizing advances in quantitative genetics and food web ecology, we provide testable predictions for how the structure and dynamics of biodiversity will respond to climate change.

Accurate, ultra-low coverage genome reconstruction and association studies in Hybrid Swarm mapping populations.

Genetic association studies seek to uncover the link between genotype and phenotype, and often utilize inbred reference panels as a replicable source of genetic variation. However, inbred reference panels can differ substantially from wild populations in their genotypic distribution, patterns of linkage-disequilibrium, and nucleotide diversity. As a result, associations discovered using inbred reference panels may not reflect the genetic basis of phenotypic variation in natural populations. To address this problem, we evaluated a mapping population design where dozens to hundreds of inbred lines are outbred for few generations, which we call the Hybrid Swarm. The Hybrid Swarm approach has likely remained underutilized relative to pre-sequenced inbred lines due to the costs of genome-wide genotyping. To reduce sequencing costs and make the Hybrid Swarm approach feasible, we developed a computational pipeline that reconstructs accurate whole genomes from ultra-low-coverage (0.05X) sequence data in Hybrid Swarm populations derived from ancestors with phased haplotypes. We evaluate reconstructions using genetic variation from the Drosophila Genetic Reference Panel as well as variation from neutral simulations. We compared the power and precision of Genome-Wide Association Studies using the Hybrid Swarm, inbred lines, recombinant inbred lines (RILs), and highly outbred populations across a range of allele frequencies, effect sizes, and genetic architectures. Our simulations show that these different mapping panels vary in their power and precision, largely depending on the architecture of the trait. The Hybrid Swam and RILs outperform inbred lines for quantitative traits, but not for monogenic ones. Taken together, our results demonstrate the feasibility of the Hybrid Swarm as a cost-effective method of fine-scale genetic mapping.

Convergence and divergence in lizard colour polymorphisms.

Colour polymorphic species are model systems for examining the evolutionary processes that generate and maintain discrete phenotypic variation in natural populations. Lizards have repeatedly evolved strikingly similar polymorphic sexual signals in distantly related lineages, providing an opportunity to examine convergence and divergence in colour polymorphism, correlated traits and associated evolutionary processes. Herein, we synthesise the extensive literature on lizard colour polymorphisms in both sexes, including recent advances in understanding of the underlying biochemical, cellular and genetic mechanisms, and correlated behavioural, physiological and life-history traits. Male throat, head or ventral colour morphs generally consist of red/orange, yellow and white/blue morphs, and sometimes mixed morphs with combinations of two colours. Despite these convergent phenotypes, there is marked divergence in correlated behavioural, physiological and life-history traits. We discuss the need for coherence in morph classification, particularly in relation to 'mixed' morphs. We highlight future research directions such as the genetic basis of convergent phenotypes and the role of environmental variation in the maintenance of polymorphism. Research in this very active field promises to continue to provide novel insights with broad significance to evolutionary biologists.

Female spider aggression is associated with genetic underpinnings of the nervous system and immune response to pathogens.

Identifying the genetic architecture underlying phenotypic variation in natural populations and assessing the consequences of polymorphisms for individual fitness are fundamental goals in evolutionary and molecular ecology. Consistent between-individual differences in behaviour have been documented for a variety of taxa. Dissecting the genetic basis of such behavioural differences is however a challenging endeavour. The molecular underpinnings of natural variation in aggression remain elusive. Here, we used comparative gene expression (transcriptome analysis and RT-PCR), genetic association analysis and pharmacological experiments to gain insight into the genetic basis of aggression in wild-caught jumping spiders (Portia labiata). We show that spider aggression is associated with a putative viral infection response gene, BTB/POZ domain-containing protein 17 (BTBDH), in addition to a putative serotonin receptor 1A (5-HT1A) gene. Spider aggression varies with virus loads, and BTBDH is upregulated in docile spiders and exhibits a genetic variant associated with aggression. We also identify a putative serotonin receptor 5-HT1A gene upregulated in docile P. labiata. Individuals that have been treated with serotonin become less aggressive, but individuals treated with a nonselective serotonin receptor antagonist (methiothepin) also reduce aggression. Further, we identify the genetic variants in the 5-HT1A gene that are associated with individual variation in aggression. We therefore conclude that co-evolution of the immune and nervous systems may have shaped the between-individual variation in aggression in natural populations of jumping spiders.

The Role of Stochasticity in the Origin of Epigenetic Variation in Animal Populations.

Epigenetic mechanisms such as DNA methylation modulate gene expression in a complex fashion are consequently recognized as among the most important contributors to phenotypic variation in natural populations of plants, animals, and microorganisms. Interactions between genetics and epigenetics are multifaceted and epigenetic variation stands at the crossroad between genetic and environmental variance, which make these mechanisms prominent in the processes of adaptive evolution. DNA methylation patterns depend on the genotype and can be reshaped by environmental conditions, while transgenerational epigenetic inheritance has been reported in various species. On the other hand, DNA methylation can influence the genetic mutation rate and directly affect the evolutionary potential of a population. The origin of epigenetic variance can be attributed to genetic, environmental, or stochastic factors. Generally less investigated than the first two components, variation lacking any predictable order is nevertheless present in natural populations and stochastic epigenetic variation, also referred to spontaneous epimutations, can sustain phenotypic diversity. Here, potential sources of such stochastic epigenetic variability in animals are explored, with a focus on DNA methylation. To this day, quantifying the importance of stochasticity in epigenetic variability remains a challenge. However, comparisons between the mutation and the epimutation rates showed a high level of the latter, suggesting a significant role of spontaneous epimutations in adaptation. The implications of stochastic epigenetic variability are multifold: by affecting development and subsequently phenotype, random changes in epigenetic marks may provide additional phenotypic diversity, which can help natural populations when facing fluctuating environments. In isogenic lineages and asexually reproducing organisms, poor or absent genetic diversity can hence be tolerated. Further implication of stochastic epigenetic variability in adaptation is found in bottlenecked invasive species populations and populations using a bet-hedging strategy.

Population Genomics on the Fly: Recent Advances in Drosophila.

Drosophila melanogaster, a small dipteran of African origin, represents one of the best-studied model organisms. Early work in this system has uniquely shed light on the basic principles of genetics and resulted in a versatile collection of genetic tools that allow to uncover mechanistic links between genotype and phenotype. Moreover, given its worldwide distribution in diverse habitats and its moderate genome-size, Drosophila has proven very powerful for population genetics inference and was one of the first eukaryotes whose genome was fully sequenced. In this book chapter, we provide a brief historical overview of research in Drosophila and then focus on recent advances during the genomic era. After describing different types and sources of genomic data, we discuss mechanisms of neutral evolution including the demographic history of Drosophila and the effects of recombination and biased gene conversion. Then, we review recent advances in detecting genome-wide signals of selection, such as soft and hard selective sweeps. We further provide a brief introduction to background selection, selection of noncoding DNA and codon usage and focus on the role of structural variants, such as transposable elements and chromosomal inversions, during the adaptive process. Finally, we discuss how genomic data helps to dissect neutral and adaptive evolutionary mechanisms that shape genetic and phenotypic variation in natural populations along environmental gradients. In summary, this book chapter serves as a starting point to Drosophila population genomics and provides an introduction to the system and an overview to data sources, important population genetic concepts and recent advances in the field.

Multiple trans QTL and one cis-regulatory deletion are associated with the differential expression of cone opsins in African cichlids

BackgroundDissecting the genetic basis of phenotypic diversity is one of the fundamental goals in evolutionary biology. Despite growing evidence for gene expression divergence being responsible for the evolution of complex traits, knowledge about the proximate genetic causes underlying these traits is still limited. African cichlids have diverse visual systems, with different species expressing different combinations of seven cone opsin genes. Using opsin expression variation in African cichlids as a model for gene expression evolution, this study aims to investigate the genetic architecture of opsin expression divergence in this group.ResultsResults from a genome-wide linkage mapping on the F2 progeny of an intergeneric cross, between two species with differential opsin expression show that opsins in Lake Malawi cichlids are controlled by multiple quantitative trait loci (QTLs). Most of these QTLs are located in trans to the opsins except for one cis-QTL for SWS1 on LG17. A closer look at this major QTL revealed the presence of a 691 bp deletion in the promoter of the SWS1 opsin (located 751 bp upstream of the start site) that is associated with a decrease in its expression. Phylogenetic footprinting indicates that the region spanning the deletion harbors a microRNA miR-729 and a conserved non-coding element (CNE) that also occurs in zebrafish and other teleosts. This suggests that the deletion might contain ancestrally preserved regulators that have been tuned for SWS1 gene expression in Lake Malawi. While this deletion is not common, it does occur in several other species within the lake.ConclusionsDifferential expression of cichlid opsins is associated with multiple overlapping QTL, with all but one in trans to the opsins they regulate. The one cis-acting factor is a deletion in the promoter of the SWS1 opsin, suggesting that ancestral polymorphic deletions may contribute to cichlid’s visual diversity. In addition to expanding our understanding of the molecular landscape of opsin expression in African cichlids, this study sheds light on the molecular mechanisms underlying phenotypic variation in natural populations.

Gene buddies: linked balanced polymorphisms reinforce each other even in the absence of epistasis.

The fates of genetic polymorphisms maintained by balancing selection depend on evolutionary dynamics at linked sites. While coevolution across linked, epigenetically-interacting loci has been extensively explored, such supergenes may be relatively rare. However, genes harboring adaptive variation can occur in close physical proximity while generating independent effects on fitness. Here, I present a model in which two linked loci without epistasis are both under balancing selection for unrelated reasons. Using forward-time simulations, I show that recombination rate strongly influences the retention of adaptive polymorphism, especially for intermediate selection coefficients. A locus is more likely to retain adaptive variation if it is closely linked to another locus under balancing selection, even if the two loci have no interaction. Thus, two linked polymorphisms can both be retained indefinitely even when they would both be lost to drift if unlinked. While these results may be intuitive, they have important implications for genetic architecture: clusters of mutually reinforcing genes may underlie phenotypic variation in natural populations, and such genes cannot be assumed to be functionally associated. Future studies that measure selection coefficients and recombination rates among closely linked genes will be fruitful for characterizing the extent of this phenomenon.

Success and failure in replication of genotype-phenotype associations: How does replication help in understanding the genetic basis of phenotypic variation in outbred populations?

Recent developments in sequencing technologies have facilitated genomewide mapping of phenotypic variation in natural populations. Such mapping efforts face a number of challenges potentially leading to low reproducibility. However, reproducible research forms the basis of scientific progress. We here discuss the options for replication and the reasons for potential nonreproducibility. We then review the evidence for reproducible quantitative trait loci (QTL) with a focus on natural animal populations. Existing case studies of replication fall into three categories: (i) traits that have been mapped to major effect loci (including chromosomal inversion and supergenes) by independent research teams; (ii) QTL fine-mapped in discovery populations; and (iii) attempts to replicate QTL across multiple populations. Major effect loci, in particular those associated with inversions, have been successfully replicated in several cases within and across populations. Beyond such major effect variants, replication has been more successful within than across populations, suggesting that QTL discovered in natural populations may often be population-specific. This suggests that biological causes (differences in linkage patterns, allele frequencies or context-dependencies of QTL) contribute to nonreproducibility. Evidence from other fields, notably animal breeding and QTL mapping in humans, suggests that a significant fraction of QTL is indeed reproducible in direction and magnitude at least within populations. However, there is also a large number of QTL that cannot be easily reproduced. We put forward that more studies should explicitly address the causes and context-dependencies of QTL signals, in particular to disentangle linkage differences, allele frequency differences and gene-by-environment interactions as biological causes of nonreproducibility of QTL, especially between populations.

Correlated evolution of thermal niches and functional physiology in tropical freshwater fishes.

The role of ecology in phenotypic and species diversification is widely documented. Nonetheless, numerous nonadaptive processes can shape realized niches and phenotypic variation in natural populations, complicating inferences about adaptive evolution at macroevolutionary scales. We tested for evolved differences in thermal tolerances and their association with the realized thermal niche (including metrics describing diurnal and seasonal patterns of temperature extremes and variability) across a genus of tropical freshwater fishes reared in a standardized environment. There was limited evolution along the thermal niche axis associated with variation in maximum temperature and in upper thermal limits. In contrast, there was considerable diversification along the first major axis of the thermal niche associated with minimum temperatures and in lower thermal limits. Across our adaptive landscape analyses, 70% of species exhibited evidence of divergence in thermal niches. Most importantly, the first two major axes of thermal niche variation were significantly correlated with variation in lower thermal limits. Our results indicate adaptation to divergent thermal niches and adaptive evolution of related functional traits, and highlight the importance of divergence in lower thermal limits for the evolution of tropical biodiversity.