Non-genetic Variation Research Articles

Nongenetic variation drives viral evolution

Viral Evolution Bacteriophage λ is a virus that infects bacteria by exploiting various membrane proteins in a well-characterized manner. Petrie et al. show how the evolution of variable folding conformations of isogenic proteins, which do not differ in their genetic sequences, contributed to λ's

Elevated polygenic burden for autism is associated with differential DNA methylation at birth

BackgroundAutism spectrum disorder (ASD) is a severe neurodevelopmental disorder characterized by deficits in social communication and restricted, repetitive behaviors, interests, or activities. The etiology of ASD involves both inherited and environmental risk factors, with epigenetic processes hypothesized as one mechanism by which both genetic and non-genetic variation influence gene regulation and pathogenesis. The aim of this study was to identify DNA methylation biomarkers of ASD detectable at birth.MethodsWe quantified neonatal methylomic variation in 1263 infants—of whom ~ 50% went on to subsequently develop ASD—using DNA isolated from archived blood spots taken shortly after birth. We used matched genotype data from the same individuals to examine the molecular consequences of ASD-associated genetic risk variants, identifying methylomic variation associated with elevated polygenic burden for ASD. In addition, we performed DNA methylation quantitative trait loci (mQTL) mapping to prioritize target genes from ASD GWAS findings.ResultsWe identified robust epigenetic signatures of gestational age and prenatal tobacco exposure, confirming the utility of DNA methylation data generated from neonatal blood spots. Although we did not identify specific loci showing robust differences in neonatal DNA methylation associated with later ASD, there was a significant association between increased polygenic burden for autism and methylomic variation at specific loci. Each unit of elevated ASD polygenic risk score was associated with a mean increase in DNA methylation of − 0.14% at two CpG sites located proximal to a robust GWAS signal for ASD on chromosome 8.ConclusionsThis study is the largest analysis of DNA methylation in ASD undertaken and the first to integrate genetic and epigenetic variation at birth. We demonstrate the utility of using a polygenic risk score to identify molecular variation associated with disease, and of using mQTL to refine the functional and regulatory variation associated with ASD risk variants.

Estimating impacts of the nuclear family and heritability of nutritional outcomes in a boat‐dwelling community

General health status is reflected in measures of height, weight, and BMI. Assessing sources of variation in these outcomes reveals population-specific variables of importance to health and nutrition. We characterize the impacts of socioeconomic variables related to the nuclear family on health outcomes of boat-dwelling Shodagor children, mothers, and fathers, and to estimate the proportion of variation in height, weight, and BMI influenced by both genetic variation and nongenetic variation among household environments. Bayesian linear mixed models (LMMs) estimate heritability and household-effect variance components among the Shodagor. These models also assess the influences of specific socioeconomic predictor variables on different types of individuals within the household (children, mothers, and fathers). Overall, models explain 61.7% of variation in height, 59.4% in weight, and 65.8% in BMI for this sample of Shodagor. Mother's decision-making and household income have expected, positive associations with children's weight and BMI. Number of children has an unexpected positive relationship to children's height and a negative relationship to father's BMI. Genetic variation explains less than 26% of phenotypic variation for each of these traits on average. Our results show that resource flows and distributions within Shodagor households account for a significant amount of variance in nutritional outcomes. Problems commonly associated with increasing market integration may lead to negative outcomes for children, while mother's autonomy may lead to positive outcomes. Our models also indicate that environmental factors account for more variation in these outcomes than expected, relative to genetics, and we discuss the implications.

Spontaneous nongenetic variation of group size creates cheater-free groups of social microbes

Social microbes are exposed to cheaters that exploit the advantages of cooperative actions without paying their fair share. Upon starvation, myxobacterial cells cooperatively aggregate into discrete fruiting bodies containing stress-resistant spores. Fruiting bodies formed from a genetically identical population can vary greatly in the number of spores that they carry. We show that such variation allows the exclusion of cheaters from some fruiting bodies and can be a mechanism to maintain cooperation.

An attempt to select non-genetic variation in resistance to starvation and reduced chill coma recovery time in Drosophila melanogaster.

Phenotypic variance is attributed to genetic and non-genetic factors, and only the former are presumed to be inherited and thus suitable for the action of selection. Although increasing amounts of data suggest that non-genetic variability may be inherited, we have limited empirical data in animals. Here, we performed an artificial selection experiment using Drosophila melanogaster inbred lines. We quantified the response to selection for a decrease in chill coma recovery time and an increase in starvation resistance. We observed a weak response to selection in the inbred and outbred lines, with variability across lines. At the end of the selection process, differential expression was detected for some genes associated with epigenetics, the piRNA pathway and canalization functions. As the selection process can disturb the canalization process and increase the phenotypic variance of developmental traits, we also investigated possible effects of the selection process on the number of scutellar bristles, fluctuating asymmetry levels and fitness estimates. These results suggest that, contrary to what was shown in plants, selection of non-genetic variability is not straightforward in Drosophila and appears to be strongly genotype dependent.

Quantitative Genetic Variation in, and Environmental Effects on, Pathogen Resistance and Temperature-Dependent Disease Severity in a Wild Trout.

Health after pathogen contact varies among individuals because of differences in pathogen load (which is limited by resistance) and disease severity in response to pathogen load (which is limited by tolerance). To understand pathogen-induced host evolution, it is critical to know not only the relative contributions of nongenetic and genetic variation to resistance and tolerance but also how they change environmentally. We quantified nongenetic and genetic variation in parasite load and the associated temperature-dependent disease among trout siblings from two rivers. We detected a genetic variance for parasite load 6.6 times as large in the colder river. By contrast, genetic variance for disease traits tended to be larger in the warmer river, where the disease was manifested more severely. The relationships between disease severity and pathogen load (tolerance) exhibited plateaus at low pathogen load and stronger steepening slopes at high pathogen load in the warmer river. Our study demonstrates the environmental influence on disease severity, nongenetic and genetic variance for health-damage-limiting host abilities, and the shape of tolerance curves. Environmental variability is predicted to govern the presence and intensity of selection, change the relative contributions of nongenetic and genetic variance, and therefore hamper evolution toward more resistant and tolerant hosts.

An independent component analysis confounding factor correction framework for identifying broad impact expression quantitative trait loci.

Genome-wide expression Quantitative Trait Loci (eQTL) studies in humans have provided numerous insights into the genetics of both gene expression and complex diseases. While the majority of eQTL identified in genome-wide analyses impact a single gene, eQTL that impact many genes are particularly valuable for network modeling and disease analysis. To enable the identification of such broad impact eQTL, we introduce CONFETI: Confounding Factor Estimation Through Independent component analysis. CONFETI is designed to address two conflicting issues when searching for broad impact eQTL: the need to account for non-genetic confounding factors that can lower the power of the analysis or produce broad impact eQTL false positives, and the tendency of methods that account for confounding factors to model broad impact eQTL as non-genetic variation. The key advance of the CONFETI framework is the use of Independent Component Analysis (ICA) to identify variation likely caused by broad impact eQTL when constructing the sample covariance matrix used for the random effect in a mixed model. We show that CONFETI has better performance than other mixed model confounding factor methods when considering broad impact eQTL recovery from synthetic data. We also used the CONFETI framework and these same confounding factor methods to identify eQTL that replicate between matched twin pair datasets in the Multiple Tissue Human Expression Resource (MuTHER), the Depression Genes Networks study (DGN), the Netherlands Study of Depression and Anxiety (NESDA), and multiple tissue types in the Genotype-Tissue Expression (GTEx) consortium. These analyses identified both cis-eQTL and trans-eQTL impacting individual genes, and CONFETI had better or comparable performance to other mixed model confounding factor analysis methods when identifying such eQTL. In these analyses, we were able to identify and replicate a few broad impact eQTL although the overall number was small even when applying CONFETI. In light of these results, we discuss the broad impact eQTL that have been previously reported from the analysis of human data and suggest that considerable caution should be exercised when making biological inferences based on these reported eQTL.

Unexpected Nongenetic Individual Heterogeneity and Trait Covariance in Daphnia and Its Consequences for Ecological and Evolutionary Dynamics.

Individual differences in genetics, age, or environment can cause tremendous differences in individual life-history traits. This individual heterogeneity generates demographic heterogeneity at the population level, which is predicted to have a strong impact on both ecological and evolutionary dynamics. However, we know surprisingly little about the sources of individual heterogeneity for particular taxa or how different sources scale up to impact ecological and evolutionary dynamics. Here we experimentally study the individual heterogeneity that emerges from both genetic and nongenetic sources in a species of freshwater zooplankton across a large gradient of food quality. Despite the tight control of environment, we still find that the variation from nongenetic sources is greater than that from genetic sources over a wide range of food quality and that this variation has strong positive covariance between growth and reproduction. We evaluate the general consequences of genetic and nongenetic covariance for ecological and evolutionary dynamics theoretically and find that increasing nongenetic variation slows evolution independent of the correlation in heritable life-history traits but that the impact on ecological dynamics depends on both nongenetic and genetic covariance. Our results demonstrate that variation in the relative magnitude of nongenetic versus genetic sources of variation impacts the predicted ecological and evolutionary dynamics.

Correction to 'Eco-evolutionary dynamics in urbanized landscapes: evolution, species sorting and the change in zooplankton body size along urbanization gradients'.

You have accessMoreSectionsView PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail Cite this article Brans Kristien I., Govaert Lynn, Engelen Jessie M. T., Gianuca Andros T., Souffreau Caroline and De Meester Luc 2017Correction to ‘Eco-evolutionary dynamics in urbanized landscapes: evolution, species sorting and the change in zooplankton body size along urbanization gradients’Phil. Trans. R. Soc. B3722016054020160540http://doi.org/10.1098/rstb.2016.0540SectionYou have accessCorrectionCorrection to ‘Eco-evolutionary dynamics in urbanized landscapes: evolution, species sorting and the change in zooplankton body size along urbanization gradients’ Kristien I. Brans Kristien I. Brans Google Scholar Find this author on PubMed Search for more papers by this author , Lynn Govaert Lynn Govaert Google Scholar Find this author on PubMed Search for more papers by this author , Jessie M. T. Engelen Jessie M. T. Engelen Google Scholar Find this author on PubMed Search for more papers by this author , Andros T. Gianuca Andros T. Gianuca Google Scholar Find this author on PubMed Search for more papers by this author , Caroline Souffreau Caroline Souffreau Google Scholar Find this author on PubMed Search for more papers by this author and Luc De Meester Luc De Meester Google Scholar Find this author on PubMed Search for more papers by this author Kristien I. Brans Kristien I. Brans Google Scholar Find this author on PubMed Search for more papers by this author , Lynn Govaert Lynn Govaert Google Scholar Find this author on PubMed Search for more papers by this author , Jessie M. T. Engelen Jessie M. T. Engelen Google Scholar Find this author on PubMed Search for more papers by this author , Andros T. Gianuca Andros T. Gianuca Google Scholar Find this author on PubMed Search for more papers by this author , Caroline Souffreau Caroline Souffreau Google Scholar Find this author on PubMed Search for more papers by this author and Luc De Meester Luc De Meester Google Scholar Find this author on PubMed Search for more papers by this author Published:05 April 2017https://doi.org/10.1098/rstb.2016.0540This article corrects the followingResearch ArticleEco-evolutionary dynamics in urbanized landscapes: evolution, species sorting and the change in zooplankton body size along urbanization gradientshttps://doi.org/10.1098/rstb.2016.0030 Kristien I. Brans, Lynn Govaert, Jessie M. T. Engelen, Andros T. Gianuca, Caroline Souffreau and Luc De Meester volume 372issue 1712Philosophical Transactions of the Royal Society B: Biological Sciences19 January 2017Phil. Trans. R. Soc. B372, 20160030. (Published online 5 December 2016) (doi:10.1098/rstb.2016.0030)There is an error in §3c. ITVOTHER represents non-genetic phenotypic trait variation due to other environmental gradients or ontogenetic changes. The corrected paragraph is provided here.(c) The relative contribution of genotypic trait variation, non-genetic intraspecific trait variation and interspecific trait turnoverFor communities in which D. magna was present, a tendency towards an increased average community body size was detected with increasing levels of urbanization (figure 4a, 3200 m scale), similar to the pattern found for the total set of communities dominated by large species. Owing to the low number of communities, however, the full model was not significant (SPT + ITV, p = 0.423, electronic supplementary material, table SA6; for results without outlier removal, see the electronic supplementary material, table SB5 and figure SB8). ITV of D. magna explained 32.43% of the total observed trait turnover along the urbanization gradient (marginally non-significant, p = 0.056, electronic supplementary material, table SA6). ITV was clearly the larger contributor, explaining 95.78% of the total variation explained by both ITV and SPT together. Including genotypic trait values at 20°C and 24°C in the analysis enabled us to disentangle three types of ITV along the urbanization gradient: genotypic trait variation (GTV), non-genetic phenotypic trait variation due to increased temperatures (ITVPLAST-T) and non-genetic phenotypic trait variation due to other environmental gradients or ontogenetic changes (ITVOTHER; figure 4b). Only the latter component showed a significant contribution to the observed increase in average community body size (electronic supplementary material, table SA6, p = 0.047). ITVOTHER explained 92.89% of the total explained variation by all trait components, while GTV and SPT contributed 4.55% and 2.56%, respectively. Regression analysis on the difference in D. magna body size measurements on all individuals (i.e. including juveniles) versus adults only plotted against degree of urbanization, suggests that the large impact of ITVOTHER might be due to a change in relative abundance of juveniles along the urbanization gradient (β1 = 20.048, p = 0.032; electronic supplementary material, figure SA6). Previous Article VIEW FULL TEXT DOWNLOAD PDF FiguresRelatedReferencesDetailsRelated articlesEco-evolutionary dynamics in urbanized landscapes: evolution, species sorting and the change in zooplankton body size along urbanization gradients19 January 2017Philosophical Transactions of the Royal Society B: Biological Sciences This Issue05 April 2017Volume 372Issue 1717Theme issue ‘Vision in dim light’ compiled and edited by David O'Carroll and Eric Warrant Article InformationDOI:https://doi.org/10.1098/rstb.2016.0540PubMed:28193824Published by:Royal SocietyPrint ISSN:0962-8436Online ISSN:1471-2970History: Published online05/04/2017Published in print05/04/2017 License:© 2017 The Author(s)Published by the Royal Society. All rights reserved. Citations and impact Subjectsecology

Phenotypic Heterogeneity in Mycobacterium tuberculosis.

The interaction between the host and the pathogen is extremely complex and is affected by anatomical, physiological, and immunological diversity in the microenvironments, leading to phenotypic diversity of the pathogen. Phenotypic heterogeneity, defined as nongenetic variation observed in individual members of a clonal population, can have beneficial consequences especially in fluctuating stressful environmental conditions. This is all the more relevant in infections caused by Mycobacterium tuberculosis wherein the pathogen is able to survive and often establish a lifelong persistent infection in the host. Recent studies in tuberculosis patients and in animal models have documented the heterogeneous and diverging trajectories of individual lesions within a single host. Since the fate of the individual lesions appears to be determined by the local tissue environment rather than systemic response of the host, studying this heterogeneity is very relevant to ensure better control and complete eradication of the pathogen from individual lesions. The heterogeneous microenvironments greatly enhance M. tuberculosis heterogeneity influencing the growth rates, metabolic potential, stress responses, drug susceptibility, and eventual lesion resolution. Single-cell approaches such as time-lapse microscopy using microfluidic devices allow us to address cell-to-cell variations that are often lost in population-average measurements. In this review, we focus on some of the factors that could be considered as drivers of phenotypic heterogeneity in M. tuberculosis as well as highlight some of the techniques that are useful in addressing this issue.

Stochasticity in the Genotype-Phenotype Map: Implications for the Robustness and Persistence of Bet-Hedging.

Nongenetic variation in phenotypes, or bet-hedging, has been observed as a driver of drug resistance in both bacterial infections and cancers. Here, we study how bet-hedging emerges in genotype–phenotype (GP) mapping through a simple interaction model: a molecular switch. We use simple chemical reaction networks to implement stochastic switches that map gene products to phenotypes, and investigate the impact of structurally distinct mappings on the evolution of phenotypic heterogeneity. Bet-hedging naturally emerges within this model, and is robust to evolutionary loss through mutations to both the expression of individual genes, and to the network itself. This robustness explains an apparent paradox of bet-hedging—why does it persist in environments where natural selection necessarily acts to remove it? The structure of the underlying molecular mechanism, itself subject to selection, can slow the evolutionary loss of bet-hedging to ensure a survival mechanism against environmental catastrophes even when they are rare. Critically, these properties, taken together, have profound implications for the use of treatment-holidays to combat bet-hedging-driven resistant disease, as the efficacy of breaks from treatment will ultimately be determined by the structure of the GP mapping.

Modeling genetic and nongenetic variation of feed efficiency and its partial relationships between component traits as a function of management and environmental factors

Feed efficiency (FE), characterized as the fraction of feed nutrients converted into salable milk or meat, is of increasing economic importance in the dairy industry. We conjecture that FE is a complex trait whose variation and relationships or partial efficiencies (PE) involving the conversion of dry matter intake to milk energy and metabolic body weight may be highly heterogeneous across environments or management scenarios. In this study, a hierarchical Bayesian multivariate mixed model was proposed to jointly infer upon such heterogeneity at both genetic and nongenetic levels on PE and variance components (VC). The heterogeneity was modeled by embedding mixed effects specifications on PE and VC in addition to those directly specified on the component traits. We validated the model by simulation and applied it to a joint analysis of a dairy FE consortium data set with 5,088 Holstein cows from 13 research stations in Canada, the Netherlands, the United Kingdom, and the United States. Although no differences were detected among research stations for PE at the genetic level, some evidence was found of heterogeneity in residual PE. Furthermore, substantial heterogeneity in VC across stations, parities, and ration was observed with heritability estimates of FE ranging from 0.16 to 0.46 across stations.

Exploiting nongenetic cell-to-cell variation for enhanced biosynthesis.

Biosynthesis enables renewable production of manifold compounds, yet often biosynthetic performance must be improved for it to be economically feasible. Nongenetic, cell-to-cell variations in protein and metabolite concentrations are naturally inherent, suggesting the existence of both high- and low-performance variants in all cultures. Although having an intrinsic source of low performers might cause suboptimal ensemble biosynthesis, the existence of high performers suggests an avenue for performance enhancement. Here we develop in vivo population quality control (PopQC) to continuously select for high-performing, nongenetic variants. We apply PopQC to two biosynthetic pathways using two alternative design principles and demonstrate threefold enhanced production of both free fatty acid (FFA) and tyrosine. We confirm that PopQC improves ensemble biosynthesis by selecting for nongenetic high performers. Additionally, we use PopQC in fed-batch FFA production and achieve 21.5 g l(-1) titer and 0.5 g l(-1) h(-1) productivity. Given the ubiquity of nongenetic variation, PopQC should be applicable to a variety of metabolic pathways for enhanced biosynthesis.

Factors influencing degree of glycosylation and phosphorylation of caseins in individual cow milk samples

The aim of this study was to examine variations in posttranslational modifications (PTM) of caseins (CN) in milk from individual cows and determine how these differ between breeds, across lactation, and between variants. Furthermore, we examined the variation of casein PTM in relation to rennet coagulation properties of milk. In total, detailed protein composition of milk from 892 Danish Holstein and Jersey cows was determined by liquid chromatography/electrospray ionization-mass spectrometry. The method measured relative contents of the main milk proteins as well as several variants and PTM. The results showed that the 2 breeds had distinct milk protein composition. Milk from Danish Holstein cows was mainly characterized by higher relative contents of β-CN, α-lactalbumin (α-LA), and β-lactoglobulin, and a higher fraction of glycosylated κ-CN (G κ-CN), whereas milk from Danish Jersey cows was characterized by higher relative contents of κ-CN, αS2-CN, and the less phosphorylated forms of αS1-CN and αS2-CN. Univariate linear models including days in milk and parity as class effects showed variation in the detailed protein profile across and between lactations; in particular, changes in the degree of glycosylation of κ-CN were pronounced, but changes in αS1-CN 8P to total αS1-CN and αS2-CN 11P to αS2-CN were also observed over lactation for both breeds. The phosphorylated forms of αS1-CN and αS2-CN were, to some extent, correlated. Further, the κ-CN BB genotype was associated with higher relative contents of both unglycosylated κ-CN (UG κ-CN) and G κ-CN compared with κ-CN AA; κ-CN AB showed intermediate results in both breeds. The influence of protein composition on rennet coagulation properties was explored based on 4 classes for curd firming rate: noncoagulation, and poor, average, and good coagulation. The results revealed breed differences: Holstein milk, higher relative content of κ-CN to total protein, and higher content of G κ-CN were associated with improved milk coagulation. In contrast, relative content of α-LA was the main component associated with milk coagulation properties in Danish Jerseys and it was shown to affect milk coagulation properties negatively. In addition, variation in phosphorylation degrees of αS1-CN also played a role. This study demonstrates that although the genetic influence of glycosylation seems to be the same in both breeds, nongenetic variation differs, which is further reflected in different associations with milk coagulation properties.

Asymmetrical Damage Partitioning in Bacteria: A Model for the Evolution of Stochasticity, Determinism, and Genetic Assimilation.

Non-genetic phenotypic variation is common in biological organisms. The variation is potentially beneficial if the environment is changing. If the benefit is large, selection can favor the evolution of genetic assimilation, the process by which the expression of a trait is transferred from environmental to genetic control. Genetic assimilation is an important evolutionary transition, but it is poorly understood because the fitness costs and benefits of variation are often unknown. Here we show that the partitioning of damage by a mother bacterium to its two daughters can evolve through genetic assimilation. Bacterial phenotypes are also highly variable. Because gene-regulating elements can have low copy numbers, the variation is attributed to stochastic sampling. Extant Escherichia coli partition asymmetrically and deterministically more damage to the old daughter, the one receiving the mother’s old pole. By modeling in silico damage partitioning in a population, we show that deterministic asymmetry is advantageous because it increases fitness variance and hence the efficiency of natural selection. However, we find that symmetrical but stochastic partitioning can be similarly beneficial. To examine why bacteria evolved deterministic asymmetry, we modeled the effect of damage anchored to the mother’s old pole. While anchored damage strengthens selection for asymmetry by creating additional fitness variance, it has the opposite effect on symmetry. The difference results because anchored damage reinforces the polarization of partitioning in asymmetric bacteria. In symmetric bacteria, it dilutes the polarization. Thus, stochasticity alone may have protected early bacteria from damage, but deterministic asymmetry has evolved to be equally important in extant bacteria. We estimate that 47% of damage partitioning is deterministic in E. coli. We suggest that the evolution of deterministic asymmetry from stochasticity offers an example of Waddington’s genetic assimilation. Our model is able to quantify the evolution of the assimilation because it characterizes the fitness consequences of variation.

Intra-tumor heterogeneity of cancer cells and its implications for cancer treatment.

Recent studies have revealed extensive genetic and non-genetic variation across different geographical regions of a tumor or throughout different stages of tumor progression, which is referred to as intra-tumor heterogeneity. Several causes contribute to this phenomenon, including genomic instability, epigenetic alteration, plastic gene expression, signal transduction, and microenvironmental differences. These variables may affect key signaling pathways that regulate cancer cell growth, drive phenotypic diversity, and pose challenges to cancer treatment. Understanding the mechanisms underlying this heterogeneity will support the development of effective therapeutic strategies.

Heterogeneity in genetic and nongenetic variation and energy sink relationships for residual feed intake across research stations and countries

Our long-term objective is to develop breeding strategies for improving feed efficiency in dairy cattle. In this study, phenotypic data were pooled across multiple research stations to facilitate investigation of the genetic and nongenetic components of feed efficiency in Holstein cattle. Specifically, the heritability of residual feed intake (RFI) was estimated and heterogeneous relationships between RFI and traits relating to energy utilization were characterized across research stations. Milk, fat, protein, and lactose production converted to megacalories (milk energy; MilkE), dry matter intakes (DMI), and body weights (BW) were collected on 6,824 lactations from 4,893 Holstein cows from research stations in Scotland, the Netherlands, and the United States. Weekly DMI, recorded between 50 to 200 d in milk, was fitted as a linear function of MilkE, BW0.75, and change in BW (ΔBW), along with parity, a fifth-order polynomial on days in milk (DIM), and the interaction between this polynomial and parity in a first-stage model. The residuals from this analysis were considered to be a phenotypic measure of RFI. Estimated partial regression coefficients of DMI on MilkE and on BW0.75 ranged from 0.29 to 0.47kg/Mcal for MilkE across research stations, whereas estimated partial regression coefficients on BW0.75 ranged from 0.06 to 0.16kg/kg0.75. Estimated partial regression coefficients on ΔBW ranged from 0.06 to 0.39 across stations. Heritabilities for country-specific RFI were based on fitting second-stage random regression models and ranged from 0.06 to 0.24 depending on DIM. The overall heritability estimate across all research stations and all DIM was 0.15±0.02, whereas an alternative analysis based on combining the first- and second-stage model as 1 model led to an overall heritability estimate of 0.18±0.02. Hence future genomic selection programs on feed efficiency appear to be promising; nevertheless, care should be taken to allow for potentially heterogeneous variance components and partial relationships between DMI and other energy sink traits across environments when determining RFI.

Environmentally induced (co)variance in sperm and offspring phenotypes as a source of epigenetic effects.

Traditionally, it has been assumed that sperm are a vehicle for genes and nothing more. As such, the only source of variance in offspring phenotype via the paternal line has been genetic effects. More recently, however, it has been shown that the phenotype or environment of fathers can affect the phenotype of offspring, challenging traditional theory with implications for evolution, ecology and human in vitro fertilisation. Here, I review sources of non-genetic variation in the sperm phenotype and evidence for co-variation between sperm and offspring phenotypes. I distinguish between two environmental sources of variation in sperm phenotype: the pre-release environment and the post-release environment. Pre-release, sperm phenotypes can vary within species according to male phenotype (e.g. body size) and according to local conditions such as the threat of sperm competition. Post-release, the physicochemical conditions that sperm experience, either when freely spawned or when released into the female reproductive tract, can further filter or modify sperm phenotypes. I find evidence that both pre- and post-release sperm environments can affect offspring phenotype; fertilisation is not a new beginning – rather, the experiences of sperm with the father and upon release can drive variation in the phenotype of the offspring. Interestingly, there was some evidence for co-variation between the stress resistance of sperm and the stress resistance of offspring, though more studies are needed to determine whether such effects are widespread. Overall, it appears that environmentally induced covariation between sperm and offspring phenotypes is non-negligible and further work is needed to determine their prevalence and strength.

Female transcriptomic response to male genetic and nongenetic ejaculate variation

Postcopulatory variation in reproductive success is fundamental for sexual selection. Because evolutionary change is impossible without a heritable basis for variation, the study of postcopulatory variation has mainly focused on genetic differences between males, that is, the effect of sperm competition or differential female responses toward male genotypes (cryptic female choice). The role of environmental components in shaping postcopulatory variation in reproductive success is well known, for example, in the form of damaging lifestyle effects on sperm, but their effect on eliciting female responses has rarely been tested, as has its relative significance compared with male genotypic effects. Here we provide such a test in bedbugs, a species where cryptic female choice has been hypothesized to be directed toward specific sperm genotypes. We measured female transcriptomic responses after experimentally controlling the male genetic and environmental component of the ejaculate. For identical female genetic background and identical male age at mating, we analyzed female gene expression in response to insemination with sperm of 3 different inbred populations (genotypes), each exposed to 1 of 2 environmental treatments (sperm storage duration in the male). Females responded mainly to environmental variation: >15 times more genes were differentially expressed, including stress response genes, compared with male genotypic variation. Our results suggest that postcopulatory natural selection exists and plays a significant role in the evolution and diversification of reproductive traits. Our results add complexity to testing the cryptic female choice hypothesis and show that nongenetic ejaculate effects are an important but underappreciated source of variation in biology.

MSH1-induced non-genetic variation provides a source of phenotypic diversity in Sorghum bicolor.

MutS Homolog 1 (MSH1) encodes a plant-specific protein that functions in mitochondria and chloroplasts. We showed previously that disruption or suppression of the MSH1 gene results in a process of developmental reprogramming that is heritable and non-genetic in subsequent generations. In Arabidopsis, this developmental reprogramming process is accompanied by striking changes in gene expression of organellar and stress response genes. This developmentally reprogrammed state, when used in crossing, results in a range of variation for plant growth potential. Here we investigate the implications of MSH1 modulation in a crop species. We found that MSH1-mediated phenotypic variation in Sorghum bicolor is heritable and potentially valuable for crop breeding. We observed phenotypic variation for grain yield, plant height, flowering time, panicle architecture, and above-ground biomass. Focusing on grain yield and plant height, we found some lines that appeared to respond to selection. Based on amenability of this system to implementation in a range of crops, and the scope of phenotypic variation that is derived, our results suggest that MSH1 suppression provides a novel approach for breeding in crops.