Biology subjects

Rego, A.

Publications and source records attributed to Rego, A..

11 recordsLinked to original sources

bioRxiv2026

Experimental evolution unveils a role for structural variants and sex-specificity in the genetic architecture of lifespan

Insights into the genetic basis of lifespan evolution can link evolutionary theory with an understanding of health, disease and adaptation. We leverage the power of >200 generations of experimental evolution in a seed beetle to unveil the genomic architecture of lifespan evolution. Replicated populations evolved under regimes favoring either a short or long life, resulting in a near doubling of lifespan. Whole genome re-sequencing revealed that short- and long-lived lines were strongly differentiated (global FST = 0.41) and more than 700 genes showed consistent signs of divergent selection. Remarkably, short- and long-lived lines were consistently divergent in a large number of regions harboring copy-number variants (CNVs), involving >600 genes. The evolution of a long life involved many distinct biological processes, such as DNA fidelity, mitotic integrity, reproduction, metabolism, immunity and stress response. A pedigree-based genome scan for quantitative trait loci (QTLs) uncovered several QTLs with large effects on lifespan, but the genetic basis of a long life was dominated by a very large number of regions with medium and small effects. The genome-wide spatial association with QTL effects was, if anything, stronger for CNVs than for sequence variants. The genetic effects of QTLs on lifespan were positively correlated overall between the sexes, but four regions showed pronounced sex-differences. Our results show that structural variants play a significant role in the evolution of an extended lifespan and the highly polygenic genomic architecture is to some extent sex-specific, consistent with differences in physiology and life history tradeoffs between the sexes.

evolutionary biology↗

bioRxiv2026

Genome-wide fluctuating selection under demographic cycling in Icelandic rock ptarmigan

Understanding how natural populations adapt to continuously shifting environments is central to evolutionary biology. Multi-annual population cycles impose temporally varying selective pressures, yet disentangling the resulting genomic signals from those of sustained directional selection and genetic drift has been challenging due to a lack of high-resolution temporal data. Here we investigate the genomic consequences of demographic cycling in a population of rock ptarmigan (Lagopus muta) from northeastern Iceland. We analyzed whole-genome sequences from 91 individuals sampled over an 11-year period, encompassing two population peaks (2010 and 2018) and two troughs (2007 and 2013). Testing allele frequency change at each SNP against a null model of drift and sampling, we identified candidate loci and grouped them by correlation of their temporal trajectories. Cluster trajectories fluctuated through time, and two were closely correlated with the regional census, one significantly tracking the demographic cycle, while a smaller set changed monotonically in a manner consistent with sustained directional selection. Each cluster contained loci distributed across many chromosomes, indicative of genome-wide responses to selection. The most strongly fluctuating loci overlapped candidate genes of possible functional relevance, most notably CTNNA2 (Catenin Alpha-2), which is associated with startle response and anxiety-like behaviors and may relate to predator avoidance. Our findings indicate that fluctuating selection comprises much of the temporal genomic response in this natural population, and suggest that multi-annual demographic cycles can drive rapid and widespread allele frequency change, highlighting the value of temporal genomics for clarifying the interplay between demography and natural selection in wild populations.

evolutionary biology↗

bioRxiv2026

The mode and repeatability of thermal adaptation in gene expression in the seed beetle Callosobruchus maculatus

Transcriptional plasticity can maintain organismal homeostasis but its potential to buffer negative effects from climate change remains contentious and may rely on genetic adaptation. Theory predicts two general outcomes: genetic reinforcement, where adaptive plasticity is enhanced by genetic adaptation; or genetic compensation, where genetic adaptation reverses maladaptive plasticity. Here, we explored the prevalence, repeatability, and molecular basis of compensation and reinforcement of gene expression responses to temperature using experimental evolution in the beetle pest, Callosobruchus maculatus. We evolved lines from three genetic backgrounds under hot or cold conditions and compared them to ancestral lines after 80-135 generations. Cold adaptation was dominated by genetic compensation, revealing a highly repeatable mode of adaptation across backgrounds, however, the underlying genes and their biological functions were largely idiosyncratic. In contrast, heat adaptation showed a less consistent mode, combining compensation and reinforcement, but greater repeatability at the level of genes and their functions. Network analysis identified many heat reinforcement genes as hubs and strongly temperature dependent, suggestive of roles in orchestrated adaptive thermal plasticity, potentially explaining their high repeatability. Genomic analyses identified repeatable allele frequency changes at both hot and cold compensation and reinforcement genes during experimental evolution. However, these were not causally linked to changes in expression levels, suggesting trans-regulation. There was also no broader correspondence between the level of repeatability of sequence and expression evolution across gene categories. Our findings suggest that the predictability of evolution under climate change might critically depend on the thermal range and the level of the genotype-phenotype map that is studied.

evolutionary biology↗

bioRxiv2026

AI-Accelerated Structure Elucidation of Boavistamides A-C, Cyclic Depsipeptides from a Marine Filamentous Cyanobacterium Collected in Cabo Verde

Boavistamide A (1), a new alkyne-containing cyclic depsipeptide featuring the rare 3-amino-2-methyl-7-octynoic acid (AMOYA) moiety, was discovered along with two structurally related analogs, boavistamides B and C (2 and 3), from a filamentous marine cyanobacterium collected on Boa Vista Island, Cabo Verde. Their isolation was guided by antiplasmodial activity, GNPS MS/MS molecular networking, LC-MS profiling, and dereplication using the MarinLit database. The planar structures of boavistamides A-C (1-3) were elucidated through comprehensive HRMS and 1D/2D NMR analyses, with annotation support from AI-based tools SMART-NMR 2.1 and DeepSAT. The absolute configurations were established using Marfeys analysis and L-Phe-OMe coupling, complemented by NMR-based conformational studies. Boavistamides A and B exhibited moderate antiplasmodial activity with no mammalian cell cytotoxicity. Microscopic observations and metagenomic binning identified the producer strain as belonging to the genus Okeania (Microcoleaceae). These results expand the chemical diversity of AMOYA-containing cyanobacterial metabolites and highlight the utility of integrated metabolomics and AI-assisted workflows for natural product discovery from environmental samples. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/732064v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@6577feorg.highwire.dtl.DTLVardef@1a8d656org.highwire.dtl.DTLVardef@18fc299org.highwire.dtl.DTLVardef@130d3d0_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2026

Activation-independent capture of free fatty acids at the bacterial cell envelope by BrtB

Fatty acids (FAs) are key metabolites in living organisms, shaping membrane architecture and helping cellular acclimatization to changing conditions. Bacteria synthesize FA de novo but can also reclaim them from membrane lipids or uptake them from the environment, usually converting free fatty acids (FFAs) into activated FAs that can then be further metabolized. In cyanobacteria, it is the acyl-acyl carrier protein synthetase (Aas) that activates exogenous FFAs. Yet, the cyanobacterial enzyme BrtB was recently shown to esterify, in vitro, FFAs directly onto abundant chlorinated glycolipids (bartolosides), generating bartoloside fatty acid esters (B-FAs). Whether this chemistry operates in vivo, where it occurs, and what its implications are for cell physiology has remained unclear. Here we show that in the cyanobacterium Synechocystis salina LEGE 06099, BrtB captures FFAs at the cell envelope without prior activation to generate B-FAs. We found that supplemented FFAs were converted into B-FAs within minutes. Strikingly, this response occurred with minimal changes in gene expression and little alteration of the extracellular proteome, consistent with a pathway already in place. Additionally, we observed that B-FAs can further be hydrolyzed into hydroxybartolosides - the levels of the latter metabolites increase in response to FA supply, suggesting a transient sequestration of FFA. Our results demonstrate that activation of FFA is not the only route to their cellular incorporation and identify a specialized-metabolite pathway that captures exogenous FFAs at the cyanobacterial cell envelope.

microbiology↗

bioRxiv2024

Strong Selection, but low repeatability: Temperature-specific effects on genomic predictions of adaptation

Climate warming is threatening biodiversity by increasing temperatures beyond the optima of many ectotherms. Due to the inherent non-linear relationship between temperature and the rate of cellular processes, such shifts towards hot temperature are predicted to impose stronger selection compared to corresponding shifts toward cold temperature. This suggests that when adaptation to warming occurs, it should be relatively rapid and predictable. Here, we tested this hypothesis from the level of single-nucleotide polymorphisms to life-history traits, by conducting an evolve-and-resequence experiment on three genetic backgrounds of the beetle, Callosobruchus maculatus. Indeed, phenotypic evolution was faster and more repeatable at hot, relative to cold, temperature. However, at the genomic level, adaptation to heat was less repeatable when compared across genetic backgrounds. As a result, genomic predictions of phenotypic adaptation in populations exposed to hot temperature were accurate within, but not between, backgrounds. These results seem best explained by genetic redundancy and an increased importance of epistasis during adaptation to heat, and imply that the same mechanisms that exert strong selection and increase repeatability of phenotypic evolution at hot temperature, reduce repeatability at the genomic level. Thus, predictions of adaptation in key phenotypes from genomic data may become increasingly difficult as climates warm.

evolutionary biology↗

bioRxiv2024

Life-history adaptation under climate warming magnifies the agricultural footprint of a cosmopolitan insect pest

Climate change is affecting population growth rates of ectothermic pests with potentially dire consequences for agriculture, but how rapid genetic adaptation impacts these dynamics remains unclear. To address this challenge, we predicted how climate change adaptation in life-history traits of insect pests may affect future agricultural yields by unifying thermodynamics based on first principles with classic life-history theory. Our model predicts that warming temperatures favour changes in resource allocation decisions coupled with increased larval host consumption, resulting in a predicted double-blow on agricultural yields under future climate change. We find support for these predictions by studying thermal adaptation in life-history traits and underlying gene expression in the wide-spread insect pest, Callosobruchus maculatus, with five years of life-history evolution under experimental warming causing an almost two-fold increase in its predicted agricultural footprint. These results emphasize the need for integrating a mechanistic understanding of life-history evolution into forecasts of pest impact.

ecology↗

bioRxiv2024

Adaptation to complex environments reveals pervasive trade-offs and genomic targets with large pleiotropic effects

Much of our knowledge on the dynamics of adaptation comes from experimental evolution studies that expose populations to a single selective pressure. However, populations in nature rarely adapt to a single stress at a time. Instead, various biotic and abiotic factors come together to produce complex selective environments. Here, we used experimental evolution to describe adaptive dynamics in the presence of simultaneous stressors, and to quantify the evolution of trade-offs between stressors in a complex environment. We adapted populations of the yeast Saccharomyces cerevisiae to a full-factorial combination of four stressors over the course of 15 serial transfers. Rapid fitness increases were accompanied by the accumulation of mutations in genes and pathways related to specific stressors. Trade-offs evolved rapidly, with the order and mode of trade-off evolution varying between environments due to the inherent physiological and genetic basis of resistance to each stressor. Compensatory evolution for maladaptation as a result of initial trade-offs was typically mediated by fine-tuning of genes associated with the initially adapted environmental component, rather than those associated with the maladapted trait. As environmental complexity increased, mutations had increasingly broader effects across multiple biological processes. Although shared mutations at the individual SNP level were rare, recurrent mutations affecting the same genes and putative biological processes were abundant across environmental complexity. Our results suggest that adaptation in complex environments follows genetic trajectories shaped by pleiotropy and trade-offs, but these trajectories may impose lasting constraints on future adaptation.

evolutionary biology↗

bioRxiv2022

The dynamics of adaptation to stress from standing genetic variation and de novo mutations

Adaptation from standing genetic variation is an important process underlying evolution in natural populations but we rarely get the opportunity to observe the dynamics of fitness changes in real time. Here, we used the power of microbial experimental evolution and whole population sequencing to track the phenotypic and genomic changes of genetically diverse yeast populations in environments with different stress levels. We found that populations rapidly and in parallel increased in fitness in stressful environments. The founders genetic diversity was quickly depleted, however, not to the same degree in all populations and environments. Some populations fixed all ancestral variation in < 30 generations while others maintained diversity across hundreds of generations. We also observed parallelism at the gene and pathway level. Specifically, we detected up to seven genes harbouring multiple independent mutations in different populations, and a general enrichment for mutations affecting downstream effectors of the high-osmolarity-glycerol pathway in three out of four environments. Adaptation to the most stressful environment was characterised by the fast evolution of functional haploidy, likely driven by standing genetic variation. Almost 40% of all populations contained aneuploidies (losses or gains of chromosomes) at least once during experimental evolution. Some aneuploidies were maintained for hundreds of generations in parallel in different replicates, suggesting they were adaptive. This work shows that experimental evolution is a great tool to address the interplay between standing variation and the influx of de novo mutations, leading to a better understanding of the demographic and environmental drivers and constraints of a populations capacity to adapt to environmental change.

evolutionary biology↗

bioRxiv2021

Distribution and diversity of dimetal-carboxylate halogenases in cyanobacteria

Halogenation is a recurring feature in natural products, especially those from marine organisms. The selectivity with which halogenating enzymes act on their substrates renders halogenases interesting targets for biocatalyst development. Recently, CylC - the first predicted dimetal-carboxylate halogenase to be characterized - was shown to regio- and stereoselectively install a chlorine atom onto an unactivated carbon center during cylindrocyclophane biosynthesis. Homologs of CylC are also found in other characterized cyanobacterial secondary metabolite biosynthetic gene clusters. Due to its novelty in biological catalysis, selectivity and ability to perform C-H activation, this halogenase class is of considerable fundamental and applied interest. However, little is known regarding the diversity and distribution of these enzymes in bacteria. In this study, we used both genome mining and PCR-based screening to explore the genetic diversity and distribution of CylC homologs. While we found non-cyanobacterial homologs of these enzymes to be rare, we identified a large number of genes encoding CylC-like enzymes in publicly available cyanobacterial genomes and in our in-house culture collection of cyanobacteria. Genes encoding CylC homologs are widely distributed throughout the cyanobacterial tree of life, within biosynthetic gene clusters of distinct architectures. Their genomic contexts feature a variety of biosynthetic partners, including fatty-acid activation enzymes, type I or type III polyketide synthases, dialkylresorcinol-generating enzymes, monooxygenases or Rieske proteins. Our study also reveals that dimetal-carboxylate halogenases are among the most abundant types of halogenating enzymes in the phylum Cyanobacteria. This work will help to guide the search for new halogenating biocatalysts and natural product scaffolds. Data statementAll supporting data and methods have been provided within the article or through a Supplementary Material file, which includes 14 supplementary figures and 4 supplementary tables.

biochemistry↗

bioRxiv2018

Dynamics of genomic change during evolutionary rescue in the seed beetle Callosobruchus maculatus

Rapid adaptation can be necessary to prevent extinction when populations are exposed to extremely marginal or stressful environments. Factors that affect the likelihood of evolutionary rescue from extinction have been identified, but much less is known about the evolutionary dynamics and genomic basis of successful evolutionary rescue, particularly in multicellular organisms. We conducted an evolve and resequence experiment to investigate the dynamics and repeatability of evolutionary rescue at the genetic level in the cowpea seed beetle, Callosobruchus maculatus, when it is experimentally shifted to a stressful host plant, lentil (Lens culinaris). Low survival (~ 1%) at the onset of the experiment caused population decline. But adaptive evolution quickly rescued the population with survival rates climbing to 69% by the F5 generation and 90% by the F10 generation. Population genomic data showed that rescue likely was caused by rapid evolutionary change at multiple loci, with many alleles fixing or nearly fixing within five generations of selection on lentil. By comparing estimates of selection across five lentil-adapted C. maculatus populations (two new sublines and three long-established lines), we found that adaptation to lentil involves a mixture of parallel and idiosyncratic evolutionary changes. Parallelism was particularly pronounced in sublines that were formed after the parent line had passed through an initial bottleneck. Overall, our results suggest that evolutionary rescue in this system is driven by very strong selection on a modest number of loci, and these results provide empirical evidence that ecological dynamics during evolutionary rescue cause distinct evolutionary trajectories and genomic signatures relative to adaptation in less stressful environments.\n\nImpact StatementEvolutionary adaptation is an ongoing process in most populations, but when populations occupy particularly stressful or marginal environments, adaptation can be necessary to prevent extinction. Adaptation that reverses demographic decline and allows for population persistence is termed evolutionary rescue. Evolutionary rescue can prevent species loss from climate change or other environmental stresses, but it can also thwart attempts to control or eradicate agricultural pests and pathogens. Many factors affect the likelihood of evolutionary rescue, but little is known about the underlying evolutionary dynamics, particularly molecular evolutionary changes in multicellular organisms. Here we use a powerful combination of experimental evolution and genomics to track the evolutionary dynamics and genomic outcomes of evolutionary rescue. We focus on the seed beetle Callosobruchus maculatus, which is both an agricultural pest and a convenient model system. We specifically examine how this species is able to persist on a novel and very poor crop host, lentil.\n\nWe show that evolution in an experimental seed beetle populations increases survival on lentil from ~1% to >80% in fewer than a dozen generations. This rapid adaptive evolutionary change at the trait (i.e., phenotypic) level was associated with equally rapid evolution at the molecular level, with some gene variants (i.e., alleles) showing frequency shifts of around 30% in a single generation. In contrast to most other experimental evolution studies in multicellular organisms (particularly Drosophila fruit flies), we find that gene variants at multiple loci rapidly fix, that is, reach a frequency of 100%, during adaptation to lentil. Our results suggest that the dynamics and genetics of adaptation to severe conditions could be distinct from adaptation under more benign conditions. By comparing outcomes of adaptation across multiple lines and sublines, we show that repeated rapid adaptation at the trait level does not necessarily involve the same evolutionary changes at the molecular level. This limited parallelism was likely driven by extreme population bottlenecks caused by low survival in the early generations on lentil. Indeed, evolutionary changes in sublines formed after recovery from a common bottleneck were highly parallel. This coupling of demographic (i.e., ecological) and evolutionary changes during evolutionary rescue may therefore limit the predictability of evolution. Because colonization of novel environments may often occur after a bottleneck, our results could be of general significance for understanding patterns of parallel (and non-parallel) evolutionary change in nature.

evolutionary biology↗