Biology subjects

Hadfield, J. D.

Publications and source records attributed to Hadfield, J. D..

9 recordsLinked to original sources

bioRxiv2026

Fitness effects of new mutations are small and heavily confounded with non-genetic sources of variation in Escherichia coli

The distribution of fitness effects (DFE) of new mutations underpins our understanding of molecular evolution, mutation load and the maintenance of quantitative genetic variation. Most direct estimates in microbes rely on mutation-accumulation (MA) lines that harbour many mutations, so that only the mean and variance of the DFE can be inferred reliably and non-genetic ('environmental') differences between lines are usually ignored. Here we generated 192 Escherichia coli MA lines that accumulated no mutations, one mutation or more than one mutation in similar proportions. Comparing the growth rates of lines with mutations with the mutation-free controls allowed us to partition fitness variation into genetic and non-genetic components. We estimate the average selection coefficient of a single mutation is unlikely to be less than -0.0020 (with 95% credibility) - a value that is small, not significantly different from zero, and largely concordant with most previous estimates from multi-mutant MA studies, although those earlier results have often been misinterpreted as implying much larger deleterious effects. Crucially, systematic non-genetic effects among lines were an order of magnitude larger than mutational effects, and failure to model them would have biased the mean selection coefficient downwards by an order of magnitude. Our study demonstrates that spontaneous mutations in E. coli are typically only mildly deleterious and that rigorous controls for environmental effects are essential for unbiased inference of the DFE in microbial systems.

evolutionary biology↗

bioRxiv2026

Selection bias in colony-based microbial mutation accumulation lines

In microbial mutation-accumulation (MA) studies, it is widely thought that natural selection is silenced by repeated single-cell bottlenecks. In support of this claim, 40 published tests for selection bias failed to detect a deficit of non-synonymous relative to synonymous mutations in wild-type microbes. Here we show that this most likely reflects selective reporting and lack of power. Our meta-analysis of 10,856 mutations from wild-type microbial MA reveals a clear signal of selection: non-synonymous mutations are observed 7.7% less often than synonymous mutations. However, our inference of the bias is hampered by a widespread failure to consider the mutation spectrum. To overcome this, we provide a multinomial-logit model that jointly estimates the mutation spectrum and selection. By applying this to a 194-line Escherichia coli MA experiment and five previous E. coli datasets (869 mutations) we reveal a deficit of non-synonymous mutations, although the reduction is not significant. While approaches do exist for correcting for selection bias, all currently assume that microbial MA lines are grown in well-mixed liquid culture rather than as surface colonies where competition is spatially structured. Although existing theory suggests selection bias should be stronger under colony growth, using agent-based simulations we show that this actually depends on the scale over which neighbouring cells compete and how unevenly they divide: it can be weaker, equivalent to, or stronger than in homogeneous growth. While our preliminary assessment is that it is considerably stronger, quantitative predictions will require the empirical details of colony growth to be better resolved.

genetics↗

bioRxiv2026

Levels of additive genetic variation vary substantially between species

A populations ability to adapt is determined by its levels of additive genetic variance (VA), and while it is agreed that most organisms have genetic variation for most traits, the extent to which it varies between species is poorly characterised. Here we investigate this question by compiling 3209 and 1852 estimates of heritability and evolvability (the additive genetic variance divided by the square of the mean) estimates respectively, for a variety of traits, from 220 and 172 multicellular eukaryotic species. Using phylogenetic generalised linear mixed models, we find substantial and highly significant interspecific variation in evolvability. Much of the variation is explained by phylogenetic relatedness, with plants in our data having substantially higher evolvability than animals. While heritability also varies between species, the differences are more subtle, and plants are not exceptional. We investigate whether the variation in evolvability and heritability between species is due to variation in the mutation rate, effective population size, genome size, ploidy and recombination rate, but find little evidence of any factor being important. However, the confidence intervals are large suggesting that we have little power to detect any associations between these factors and our estimates of VA.

evolutionary biology↗

bioRxiv2026

Nucleotide diversity is a poor predictor of short-term adaptive potential

Significance statementThe current paradigm in conservation genetics suggests that species with the lowest molecular genetic diversity have the lowest capacity to adapt. Despite previous concern that traditional measures of molecular genetic variation are not useful predictors of adaptive potential, the conflation of genetic diversity and adaptive potential remains prevalent in both scientific literature and global policy. By combining new theory with a large dataset of genetic variation across hundreds of species, we show that molecular sequence variation is weakly related to the level of heritable variation in traits across species. This demonstrates that genetic diversity does not reliably predict adaptive potential, and highlights the urgent need to move beyond simple measures when assessing the evolutionary resilience of populations. A capacity to adapt is essential for a population to avoid extinction in a changing world and is recognised as a global conservation priority. Adaptation requires additive (heritable) genetic variation for traits that influence survival and fecundity, but measuring this variation is difficult, particularly in species of conservation concern. Instead, molecular genetic diversity is often used to infer adaptive potential. However, previous research has cast doubt on the suitability of traditional molecular markers (allozymes and microsatellites) for this purpose given their weak relationship with heritability - a common measure of additive genetic variance. Recent advances in sequencing technology have since shifted focus towards nucleotide diversity and variation in functional regions, but their practicality for predicting adaptive potential remains debated and untested. Furthermore, heritability itself is a poor proxy for adaptive potential because it depends on environmental variance. We collated 2,113 published estimates of evolvability - a measure of additive genetic variance that avoids environmental confounding - across 193 eukaryotic species, and evaluated how well evolvability is predicted by molecular diversity. We find that microsatellite and nucleotide diversity are not significantly correlated to each other, and neither predict evolvability (nucleotide diversity explains 0.7% of interspecific differences in evolvability and doubling nucleotide diversity only corresponds to a 9.2% increase in evolvability). With new theoretical work, we show that such weak associations are expected. Together, our results suggest that simple molecular measures of genetic variation are insufficient for predicting adaptive potential and continued reliance on these metrics risks misinforming conservation management.

evolutionary biology↗

bioRxiv2025

Estimating the additive genetic variance for relative fitness from changes in allele frequency

The rate of adaptation is equal to the additive genetic variance for relative fitness (VA) in the population. Estimating VA typically involves obtaining suitable measures of fitness on a large number of individuals with known pairwise relatedness. Such data are hard to collect and the results are often sensitive to the definition of fitness used. Here, we present a new method for estimating VA that does not involve making measurements of fitness on individuals, but instead tracks changes in the genetic composition of the population. First, we show that VA can readily be expressed as a function of the genome-wide diversity/linkage disequilibrium matrix and genome-wide expected change in allele frequency due to selection. We then show how independent experimental replicates can be used to infer the expected change in allele frequency due to selection and then estimate VA via a linear mixed model. Finally, using individual-based simulations, we demonstrate that our approach yields precise and accurate estimates over a range of biologically plausible scenarios. Article summaryConventional approaches for estimating the heritable component of fitness variation (VA) have steep methodological, statistical, and even definitional challenges. Here, the authors present a new method that overcomes many of these issue by modelling VA using selection-induced changes to a populations genetic composition. The authors develop novel mathematical theory and an inference approach that uses independent experimental populations derived from the same ancestral population. Individual based simulations show that this method provides unbiased and precise estimates of VA. This opens the door for future studies investigating the genomic distribution of VA, a key factor driving Darwinian evolution.

evolutionary biology↗

bioRxiv2022

The host phylogeny determines viral infectivity and replication across Staphylococcus host species

Genetic similarity between eukaryotic host species is an important determinant of the outcome of virus host shifts, where a pathogen infects a novel host species. However, it is less clear if this is the case for prokaryotes where anti-virus defences can be transmitted by horizontal gene transfer and evolve rapidly. Understanding the patterns and determinants of cross-species transmissions may provide insights into the processes underlying pathogen emergence. Here, we measure the susceptibility of 64 strains of Staphylococcus bacteria (48 strains of S. aureus and 16 non-aureus species) to the bacteriophage ISP, which is currently under investigation for use in phage therapy. Using three methods - plaque assays, optical density (OD) assays, and quantitative (q)PCR - we find that the host phylogeny explains a large proportion of the variation in susceptibility to ISP across the host panel. These patterns were consistent in models of only S. aureus strains and models with a single representative from each Staphylococcus species, suggesting that these phylogenetic effects are conserved both within and among host species. We find positive correlations between susceptibility assessed using a binary measure of plaque assay, OD, and qPCR, but not between the continuous component of plaque assay and any other method, suggesting that plaque assays alone may be inadequate to assess host range. Together, our results demonstrate the ability of bacterial host evolutionary relatedness to explain differences in susceptibility to phage infection, with implications for the development of ISP both as a phage therapy treatment and as an experimental system for the study of virus host shifts.

evolutionary biology↗

bioRxiv2020

A rare MHC haplotype confers selective advantage in a free-living ruminant

Genes within the major histocompatibility complex (MHC) are the most variable identified in vertebrates. Pathogen-mediated selection (PMS) is believed to be the main force maintaining diversity at MHC class I and II genes, but it has proven hard to demonstrate the exact PMS regime that is acting in natural populations. Demonstrating contemporary selection on MHC alleles is not trivial, and previous work has been constrained by limited genetic tools, low sample sizes and short time scales and has sometimes involved anticonservative statistical approaches. Here, we use appropriate statistical approaches to examine associations between MHC variation and several fitness measurements including total fitness (lifetime breeding success) and five fitness components, in 3400 wild Soay sheep (Ovis aries) monitored over their lifetimes between 1989 and 2012. We found haplotypes C and D were associated with decreased and increased male total fitness respectively. In terms of fitness components, juvenile survival was positively associated with haplotype divergence. Of the eight MHC haplotypes (A-H), haplotypes C and F were associated with decreased adult male breeding success and decreased adult female life span respectively. Consistent with the increased male total fitness, haplotype D, which is the rarest, has increased in frequency throughout the study period. Our results suggest that contemporary balancing selection is acting on MHC class II genes in Soay sheep and that different selection mechanisms are acting between juveniles and adults.

evolutionary biology↗

bioRxiv2018

The Evolution of Phenotypic Plasticity when Environments Fluctuate in Time and Space

Most studies have explored the evolution of plasticity when the environment, and there-fore the optimal trait, varies in time or space. When the environment varies in time and space we show that genetic adaptation to temporal fluctuations depends on the between-generation autocorrelation in the environment in exactly the same way that genetic adaptation to spatial fluctuations depends on the probability of philopatry. This is because both measure the correlation in parent-offspring environments and therefore the effectiveness of a genetic response to selection. If the capacity to genetically respond to selection is stronger in one dimension (e.g. space) then plasticity mainly evolves in response to fluctuations in the other dimension (e.g. time). If the relationship between the environments of development and selection are the same in time and space then the evolved plastic response to temporal fluctuations is useful in a spatial context and genetic differentiation in space is reduced. However, if the relationship between the environments of development and selection are different then the optimal level of plasticity is different in the two dimensions. In this case the plastic response that evolves to cope with temporal fluctuations may actually be maladaptive in space. This can result in the evolution of hyperplasticity or negative plasticity, the effects of which are mitigated by spatial genetic differentiation. However, genetic differentiation acts in opposition to plasticity resulting in counter-gradient variation. These results highlight the difficulty of making space-for-time substitutions in empirical work but identify the key parameters which need to be measured in order to test whether space-for-time substitutions are likely to be valid.

evolutionary biology↗

bioRxiv2018

Changes in temperature alter susceptibility to a virus following a host shift

Host shifts - where a pathogen jumps between different host species - are an important source of emerging infectious disease. With ongoing climate change there is an increasing need to understand the effect changes in temperature may have on emerging infectious disease. We investigated whether species susceptibilities change with temperature and ask if susceptibility is greatest at different temperatures in different species. We infected 45 species of Drosophilidae with an RNA virus and measured how viral load changes with temperature. We found the host phylogeny explained a large proportion of the variation in viral load at each temperature, with strong phylogenetic correlations between viral loads across temperature. The variance in viral load increased with temperature, whilst the mean viral load did not, such that as temperature increased the most susceptible species become more susceptible, and the least susceptible less so. We found no significant relationship between a species susceptibility across temperatures and proxies for thermal optima; critical thermal maximum and minimum or basal metabolic rate. These results suggest that whilst the rank order of species susceptibilities can remain the same with changes in temperature, the likelihood of host shifts into a given species may increase or decrease.\n\nAuthor SummaryEmerging infectious diseases are often the result of a host shift, where a pathogen jumps from one host species into another. Understanding the factors underlying host shifts is a major goal for infectious disease researchers. This effort has been further complicated by the fact that host-parasite interactions are now taking place in a period of unprecedented global climatic warming. Here, we ask how host shifts are affected by temperature by carrying out experimental infections using an RNA virus across a wide range of related species, at three different temperatures. We find that as temperature increases the most susceptible species become more susceptible, and the least susceptible less so. This has important consequences for our understanding of host shift events in a changing climate, and suggests that temperature changes may affect the likelihood of a host shift into certain species.

evolutionary biology↗