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Halliwell, B.

Publications and source records attributed to Halliwell, B..

12 recordsLinked to original sources

Non-convergent aridity adaptation despite pervasive linked selection in Eucalyptus

Whether independent lineages evolve similar genetic solutions when faced with the same environmental pressure is central to understanding how repeatable and predictable adaptation is. Answering this question is increasingly urgent as climate change intensifies drought and aridity worldwide, a shared pressure to which many species must independently adapt. Here we characterised genomic adaptation in Eucalyptus across three independent species pairs, each comprising two closely related lineages that have diverged from wetter into drier environments. Across all pairs we found concordant genome-wide landscapes of diversity and divergence, and strong evidence for pervasive linked selection. Because linked selection acts most strongly in the same conserved features of the genome, this shared architecture could concentrate differentiation in the same regions across lineages, creating an appearance of convergent adaptation. Despite this, the genomic regions associated with the transition to drier environments were largely non-convergent, with almost no sharing of outlier loci among pairs, demonstrating that each lineage adapted through a largely independent genetic route. Some convergence was instead evident at the level of biological function, indicating that lineages reached similar functional outcomes using different genes. We further identified large genomic islands of differentiation, which were dominated by the signature of linked selection rather than elevated divergence, though several harboured candidate genes within the drought and abscisic acid regulatory networks. Together, our results indicate that adaptation to aridity in Eucalyptus is complex and polygenic, and largely unpredictable at the level of individual loci.

evolutionary biology↗

Sizing up phylogenetic testing in geometric morphometrics: A case study of allometry

AbstractAccounting for phylogenetic relatedness in the analysis of shape has become a common practice, deemed necessary to factor in the non-independence between species because of common ancestry. However, when adjusting error distributions to account for relatedness, the phylogenetic-generalised-least-squares (PGLS) test can obscure an important component of variation called conservative trait correlation (CTC). This is the amount of variation in a response variable that is both attributable to a predictor variable and phylogenetically structured. If CTC represents a large amount of correlated variation, true biological associations with strong phylogenetic signal (from unrepeated evolutionary events for example) might not be supported using a PGLS. We demonstrate this effect using geometric morphometric shape analysis on 370 crania from the speciose Australian rock- wallabies (genus Petrogale). In this clade, well-recognised allometric patterns such as scaling of the braincase (Hallers rule) and snout length (craniofacial evolutionary allometry) are supported using ordinary least squares (OLS) regression, but not PGLS, indicating that important between-species shape variation is lost. We then apply two methods capable of quantifying aspects of the missing variation: variation partitioning (VARPART), which estimates the proportion of variation shared between the predictor and phylogeny, and multi- response phylogenetic mixed models (MR-PMM), which identify the strength of correlation within the phylogenetic component of trait variance. Both methods show that CTC dominates the allometric shape variation in our sample, highlighting its importance in assessing phylogenetically informed models. We suggest approaches that can consider CTC become more widely used to better understand morphology and its predictors.

evolutionary biology↗

Rethinking niche conservatism with phylogenetic location-scale models

Phylogenetic niche conservatism (PNC) describes the tendency of evolutionary lineages to retain functional traits over time, leading to closely related species exhibiting similar phenotypes and ecological niches. Traditional approaches to studying PNC focus on phylogenetic signal in trait means, often overlooking the conservation of trait variability across lineages. This oversight limits our understanding of the ecological constraints on species adaptation. Trait variance, influenced by genetic, ecological, and environmental factors, is crucial for understanding evolutionary processes and species adaptive potential. Phylogenetic location-scale models offer a promising framework to incorporate both mean and variance components of trait evolution, providing a more nuanced understanding of how ecological and evolutionary processes shape trait evolution across lineages. We apply this approach to leaf economic data for the genus Eucalyptus, demonstrating that models including predictors for both mean and variance offer greater predictive performance and deeper insights into the mechanisms of niche conservatism and ecological adaptation. Our findings highlight the importance of considering trait variance in studies of PNC and its implications for assessing species resilience to environmental change.

evolutionary biology↗

Conserved strategies underpin the replicated evoluton of aridity tolerance in trees

Predicting forest responses to climate change requires a detailed understanding of trait-environment coordination. Adaptation to environment comprises both conserved and labile components of trait variation. However, few studies explore the decomposition of trait-environment relationships in a rigorous phylogenetic framework. Combining a revised phylogeny with trait, climate and soil data to achieve unprecedented species coverage ([~]85%), we identified patterns of replicated evolution that allowed the evergreen tree genus, Eucalyptus, to rapidly radiate across Australia in response to aridification. Eucalypts from arid regions are short, produce dense wood, and have small, physically robust leaves with high nitrogen content, promoting hydraulic safety and economies in photosynthetic water use. Phylogenetic modelling reveals strong niche conservatism, with adaptation to aridity occurring primarily via clade-level divergences, followed by phylogenetically independent adjustments to local conditions. Ancestral state reconstructions accounting for trends in the paleoclimate record indicate that transitions in aridity tolerance are associated with distinct signals of environmental filtering and directional selection on functional trait variation. However, astonishing repeatability of trait changes in different clades reveals a narrow optimal solution to water availability, opening a path to predict future species distributions from phylogenetically structured trait data and signalling major implications for functional and species diversity under progressive climate change.

evolutionary biology↗

The economic strategies of superorganisms

The leaf economics spectrum links strategies of plant investment in resource-acquiring leaves to overall fitness. We test whether an economic spectrum can also explain variation in ecological strategies of ant species across environmental gradients, where colony investment in workers is analogous to plant investment in leaves. A fast return of resource investment was associated with large colonies of smaller, less robust, short-lived workers with low nitrogen:phosphorus ratios. Slow resource payback was associated with small colonies of densely built, energetically conservative and longer-lived workers with high nitrogen:phosphorus ratios. Species representing the entire economic continuum co-occurred in all communities. Phylogenetic analyses suggest genus level conservation of core investment templates. These results unify studies of plants and ants, suggesting common economic principles apply across the tree of life.

ecology↗

Reproductive and ecological adaptations to climate underpin the evolution of sociality in lizards

Identifying the environmental factors associated with group living is important for understanding how social systems originate, persist and diversify. In endothermic birds and mammals, living in social groups is associated with habitat constraints and harsh climatic conditions. We use phylogenetic comparative analyses to test whether climate and habitat have played similar roles in the evolution of social grouping in a globally distributed clade of ectothermic vertebrates, lizards (Nspecies = 1696). Social grouping was strongly associated with cool, dry climates across the lizard phylogeny. However, this climatic signature arose indirectly, by association with live birth (common in cool climates) and a reliance on rock crevices (common in dry climates), traits which increase parent-offspring associations and reduce offspring dispersal. In contrast, direct effects of cool temperature on the evolution of social grouping were marginal and restricted to live bearing species. Our results demonstrate that relationships between climate and sociality may result from climatic adaptations that go on to promote the emergence of grouping behaviour.

evolutionary biology↗

Phylogenetically conservative trait correlation: quantification and interpretation

O_LICorrelation across species between two quantitative traits, or between a trait and a habitat property, can suggest that a trait value is effective in sustaining populations in some contexts but not others. It is widely held that such correlations should be controlled for phylogeny, via phylogenetically independent contrasts PICs or phylogenetic generalised least squares PGLS. C_LIO_LITwo weaknesses of this idea are discussed. First, the phylogenetically conservative share of the correlation ought not to be excluded from consideration as potentially ecologically functional. Second, PGLS does not yield a complete or accurate breakdown of A-B covariation, because it corresponds to a generating model where B predicts variation in A but not the reverse. C_LIO_LIMulti-response mixed models using phylogenetic covariance matrices can quantify conservative trait correlation CTC, a share of covariation between traits A and B that is phylogenetically conservative. Because the evidence is from correlative data, it is not possible to split CTC into causation by phylogenetic history versus causation by continuing reciprocal selection between A and B. Moreover, it is quite likely biologically that the two influences have acted in concert, through phylogenetic niche conservatism. C_LIO_LISynthesis: The CTC concept treats phylogenetic conservatism as a conjoint interpretation alongside ongoing influence of other traits. CTC can be quantified via multi-response phylogenetic mixed models. C_LI

ecology↗

Protection against doxorubicin-induced cardiotoxicity by ergothioneine

Anthracyclines such as doxorubicin remain the first line of treatment for haematological malignancies, and breast cancers. However, the potential risk of cardiac injury by anthracyclines, which may lead to severe myopathy or heart failure, severely limits their application, and remains a challenge to ensuring curative chemotherapy. While the complex interplay between pathological pathways of anthracycline cardiotoxicity is yet to be fully understood, oxidative damage, iron overload-mediated formation of reactive oxygen species (ROS), mitochondrial dysfunction, and inflammation are all believed to be involved. The unique dietary thione, ergothioneine, while not produced in animals and humans, can be avidly absorbed and accumulated in tissues including the heart. Amongst other cytoprotective properties ergothioneine has been shown to scavenge various ROS, decrease proinflammatory mediators, chelate metal cations such as Fe2+, preventing them from partaking in redox activities, and may protect against mitochondrial damage and dysfunction. Moreover, low plasma ergothioneine levels are also strongly correlated to risk of cardiovascular events in humans, suggestive of a cardioprotective role. Taken together this highlights the potential for ergothioneine to counteract anthracycline cardiotoxicity. Here we investigate the potential of ergothioneine supplementation to protect against cardiac dysfunction in mice models of doxorubicin-induced cardiotoxicity and found that it had significant protective effects. Moreover, ergothioneine administration in a mouse breast cancer model did not exacerbate the growth of the tumour and did not interfere with the chemotherapeutic efficacy of doxorubicin. These results suggest that ergothioneine could be a viable co-therapy to alleviate the cardiotoxic effects of anthracyclines in the treatment of cancers.

physiology↗

Multi-Response Phylogenetic Mixed Models: Concepts andApplication

The scale and resolution of trait databases and molecular phylogenies is increasing rapidly. These resources permit many open questions in comparative biology to be addressed with the right statistical tools. Multi-response (MR) phylogenetic mixed models (PMM) offer great potential for multivariate analyses of trait evolution. While flexible and powerful, these methods are not often employed by researchers in ecology and evolution, reflecting a specialised and technical literature that creates barriers to usage for many biologists. Here we present a practical and accessible guide to MR-PMM. We begin with a review of single-response (SR) PMM to introduce key concepts and outline the limitations of this approach for characterizing patterns of trait co-evolution. We emphasise MR-PMM as a preferable approach to analyses involving multiple species traits, due to the explicit decomposition of trait covariance across levels in the model hierarchy. We discuss multilevel distributional models, meta-analyses, multivariate models of evolution, and extensions to non-Gaussian response traits. We highlight techniques for causal inference using precision matrices, as well as advanced topics including prior specification and latent factor models. Using simulated data and visual examples, we discuss interpretation, prediction, and model validation. We implement many of the techniques discussed in example analyses of plant functional traits to demonstrate the general utility of MR-PMM in handling complex real world datasets. Finally, we discuss the emerging synthesis of comparative techniques made possible by MR-PMM, highlight strengths and weaknesses, and offer practical recommendations to analysts. To complement this material, we provide extensive online tutorials including side-by-side model implementations in two popular R packages, MCMCglmm and brms.

evolutionary biology↗

Metabolic stress is a primary pathogenic event in transgenic Caenorhabditis elegans expressing neuronal human amyloid-β

Alzheimers disease (AD) is the most common neurodegenerative disease affecting the elderly worldwide. Mitochondrial dysfunction has been proposed as a key event in the etiology of AD. We have previously modeled amyloid-beta (A{beta})-induced mitochondrial dysfunction in a transgenic Caenorhabditis elegans strain by expressing human A{beta} peptide specifically in neurons (GRU102). Here, we focus on a deeper analysis of these metabolic changes associated with A{beta}-induced mitochondrial dysfunction. Integrating metabolomics, transcriptomics, biochemical studies and computational modeling, we identify alterations in Tricarboxylic Acid (TCA) cycle metabolism following even low-level A{beta} expression. In particular, GRU102 show reduced activity of a rate-limiting TCA cycle enzyme, alpha-ketoglutarate dehydrogenase. These defects are associated with elevation of protein carbonyl content specifically in mitochondria. Importantly, metabolic failure occurs before any significant increase in global protein aggregate is detectable. Treatment with an antidiabetes drug, Metformin, reverses A{beta}-induced metabolic defects, reduces protein aggregation and normalizes the lifespan of GRU102. Our results point to metabolic dysfunction as an early and causative event in AD pathology and a promising target for intervention.

neuroscience↗

Clonal expansion of mitochondrial DNA deletions is a private mechanism of ageing in long-lived animals

Disruption of mitochondrial metabolism and loss of mitochondrial DNA (mtDNA) integrity are widely considered as evolutionarily conserved (public) mechanisms of ageing (Lopez-Otin et al. 2013). Human ageing is associated with loss in skeletal muscle mass and function (Sarcopenia), contributing significantly to morbidity and mortality. Muscle ageing is associated with loss of mtDNA integrity. In humans, clonally expanded mtDNA deletions co-localize with sites of fiber-breakage and atrophy in skeletal muscle. mtDNA deletions may therefore play an important, possibly causal role in sarcopenia. The nematode Caenorhabditis elegans also exhibits age-dependent decline in mitochondrial function and a form of sarcopenia. However, it is unclear if mtDNA deletions play a role in C. elegans ageing. Here we report identification of 266 novel mtDNA deletions in ageing nematodes. Analysis of the mtDNA mutation spectrum and quantification of mutation burden indicates that (1) mtDNA deletions in nematode is extremely rare, (2) there is no significant age-dependent increase in mtDNA deletions and (3) there is little evidence for clonal expansion driving mtDNA deletion dynamics. Thus, mtDNA deletions are unlikely to drive the age-dependent functional decline commonly observed in C. elegans. Computational modelling of mtDNA dynamics in C. elegans indicates that the lifespan of short-lived animals such as C. elegans is likely too short to allow for significant clonal expansion of mtDNA deletions. Together, these findings suggest that clonal expansion of mtDNA deletions is likely a private mechanism of ageing predominantly relevant in long-lived animals such as humans and rhesus monkey and possibly in rodents.

genetics↗

Thermodynamic analysis of mitochondrial DNA breakpoints reveals mechanistic details of deletion mutagenesis

Broad evidence support double-strand breaks (DSBs) as initiators of mitochondrial DNA (mtDNA) deletion mutations. But the mechanism of DSB-induced deletions, including the DSB repair pathway(s) involved, remains to be established. Here, we used DNA hybridization thermodynamics to analyze misalignment lengths surrounding deletion breakpoints. Our analysis of 9,655 previously reported mammalian mtDNA deletions and 1,307 novel Caenorhabditis elegans mtDNA deletions, indicates a significant role of 0-25bp misalignments, supporting the role of erroneous non-homologous and micro-homology dependent DSB repair in deletion formation. Based on these insights we propose that DSB-induced mtDNA deletions occur via the misjoining of DSB ends and/or strand invasion of open mtDNA regions by DSB ends.

systems biology↗