The Emergence of Non-Linear Evolutionary Trade-offs and the Maintenance of Genetic Polymorphisms

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Abstract Evolutionary models of quantitative traits often assume trade-offs between beneficial and detrimental traits, requiring modelers to specify a function linking costs benefits. The choice trade-off is consequential; functions that diminishing returns (accelerating costs) typically lead single equilibrium genotypes, while decelerating evolutionary branching. Despite their importance, we still lack strong theoretical foundation base the function. To address this gap, explore how can emerge from genetic architecture trait. We developed multi-locus model disease resistance, assuming each locus had random antagonistic pleiotropic effects on resistance fecundity. used generate genotype landscapes explored additive versus epistatic architectures influenced shape Regardless epistasis, our consistently led accelerating costs. then build an resistance. Unlike other with costs, approach polymorphisms at equilibrium. Our results suggest are null for eco-evolutionary conditions required polymorphism may be more nuanced than previously believed.

Language: Английский

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A scalable adaptive quadratic kernel method for interpretable epistasis analysis in complex traits

Genome Research, Journal Year: 2024, Volume and Issue: 34(9), P. 1294 - 1303

Published: Aug. 29, 2024

Our knowledge of the contribution genetic interactions ( epistasis ) to variation in human complex traits remains limited, partly due lack efficient, powerful, and interpretable algorithms detect interactions. Recently proposed approaches for set-based association tests show promise improving power by examining aggregated effects multiple variants. Nevertheless, these methods either do not scale large Biobank data sets or interpretability. We propose QuadKAST, a scalable algorithm focused on testing pairwise interaction quadratic within small medium-sized variants (window size ≤100) trait provide quantified interpretation effects. Comprehensive simulations that QuadKAST is well-calibrated. Additionally, highly sensitive detecting loci with epistatic signals accurate its estimation applied 52 quantitative phenotypes measured ≈300,000 unrelated white British individuals UK test each 9515 protein-coding genes. 32 trait-gene pairs across 17 29 genes demonstrate statistically significant (accounting number tested). Across pairs, proportion variance explained comparable additive effects, five having ratio >1. method enables detailed investigation scale, offering new insights into role importance.

Language: Английский

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Efficient CRISPR/Cas9‐mediated genome editing in the European corn borer, Ostrinia nubilalis

Insect Molecular Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Abstract The European corn borer ( Ostrinia nubilalis ) is an agricultural pest and burgeoning model for research on speciation, seasonal adaptation insect resistance management. Although previous work in O. has identified genes associated with differences life cycle, reproduction, to Bt toxins, the general lack of a robust gene‐editing protocol been barrier functional validation candidate genes. Here, we demonstrate efficient practical methodology heritable gene mutagenesis using CRISPR/Cas9 genome editing system. Precise loss‐of‐function (LOF) mutations were generated at two circadian clock genes, period per pigment‐dispersing factor receptor pdfr ), developmental gene, prothoracicotropic hormone ptth ). Precluding need visible genetic marker, efficiency remained high across different single guide RNAs (sgRNA) germline transmission F 1 offspring approached 100%. When or dual sgRNAs injected concentration, gene‐specific phenotypic behaviour development 0 mutants. Specifically, mutants demonstrated that PER, but not PDFR, essential normal timing eclosion. PTTH significantly heavier exhibited higher incidence diapause. This will accelerate future studies function facilitate similar screens other Lepidopteran non‐model insects.

Language: Английский

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Performance of deep-learning based approaches to improve polygenic scores

Published: Oct. 23, 2024

Abstract Background/Objectives Polygenic scores (PGS), which estimate an individual’s genetic propensity for a disease or trait, have the potential to become part of genomic healthcare. In maximising predictive performance PGS, neural-network (NN) based deep learning has emerged as method intense interest model complex, nonlinear phenomena, may be adapted exploit gene-gene (G x G) and gene-environment E) interactions. Methods To infer amount nonlinearity present in phenotype, we framework using NNs, controls confounding effect correlation between variants, i.e. linkage disequilibrium (LD). We fit NN models both simulated traits 28 real anthropometric UK Biobank. Results Simulations confirmed that our adequately LD can effects, when such effects genuinely exist. Using this approach on data, found evidence small amounts due G E mildly improved prediction (r 2 ) by ∼7% ∼4%, respectively. Despite were outperformed linear regression genetic-only genetic+environmental input scenarios with ∼5% differences r , Importantly, substantial joint tagging whereby inferred was actually unaccounted additive variants. Conclusion Our results indicate usefulness NNs generating polygenic common diseases currently limited confounded LD.

Language: Английский

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The emergence of nonlinear evolutionary trade-offs and the maintenance of genetic polymorphisms

Biology Letters, Journal Year: 2024, Volume and Issue: 20(12)

Published: Dec. 1, 2024

Evolutionary models of quantitative traits often assume trade-offs between beneficial and detrimental traits, requiring modellers to specify a function linking trait values. The choice trade-off can be consequential; functions that diminishing returns (accelerating costs) typically lead single equilibrium genotypes, while decelerating costs genetic polymorphisms. Despite their importance, our current theory has little say on which are the most biologically plausible. To address this gap, we explored how determination different functions, using resistance infectious diseases as an example trait. We developed model where alleles at separate loci pleiotropically increase decreasing fecundity. then used generate genotype landscapes investigate epistasis effects function. Regardless strength epistasis, consistently led accelerating costs. incorporated into eco-evolutionary disease resistance. Unlike other with costs, approach Our results suggest strong null for evolutionary conditions required polymorphism may more nuanced than previously thought.

Language: Английский

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Shared genetic architecture of type 2 diabetes with muscle mass and function and frailty reveals comorbidity etiology and pleiotropic druggable targets

Metabolism, Journal Year: 2024, Volume and Issue: unknown, P. 156112 - 156112

Published: Dec. 1, 2024

Language: Английский

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The persistence of locally adapted polymorphisms under mutation swamping

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 22, 2024

Abstract Locally adapted traits can exhibit a wide range of genetic architectures, from pronounced divergence at few loci to small allele frequency shifts many loci. The type architecture that evolves depends strongly on migration rate, as weakly selected experience swamping and do not make stable contributions divergence. Simulations previous studies showed even when mutations are should resist swamping, the adaptation collapse become transient high mutation rates. Here, we use an analytical two-population model study how this “mutation swamping” phenomenon upon population size, strength selection, parameters determining effects. To this, developed mathematical theory based diffusion approximation predict threshold rate above which occurs, find performs well across parameter space, comparisons with individual-based simulations. most average effect size mutations, but is only minimally affected by size. Across observe occurs trait-wide 10 − 3 –10 2 , suggesting potentially relevant complex large mutational target. On other hand, apparent stability in classic examples local adaptation, our suggests per-trait rates often relatively low.

Language: Английский

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Whole-genome data uncover the basis of local adaptation with gene flow in a threatened coastal songbird

Authorea (Authorea), Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

Understanding the genetic basis of local adaptation and distribution standing variation is imperative for biodiversity conservation as species decline globally. The Atlantic song sparrow (Melospiza melodia atlantica) a specialist subspecies concern that adapted to coastal habitats eastern North America interbreeds with widespread, parapatric generalist subspecies, (M. m. melodia). Because sparrows offer an ideal opportunity explore evolutionary dynamics gene flow, we examined genomic architecture divergence using whole-genome sequencing these subspecies. We identified polygenic adaptation, candidate genes related osmoregulation, plumage pigmentation, bill size. Divergent were dispersed throughout homogenous background, demonstrating strong natural selection key force maintaining differentiation between despite flow. Notably, some located near centromeres telomeres, suggesting regions suppressed recombination may play role in maintenance flow this system. found population structure within sparrow, southern barrier islands making up portion range each island comprising distinct cluster, which inform future management decisions. This system emphasizes need high-resolution data characterize adaptive effective strategies systems extensive

Language: Английский

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Combining QTL Mapping and Multi-Omics Identify Candidate Genes for Nutritional Quality Traits during Grain Filling Stage in Maize

Phyton, Journal Year: 2024, Volume and Issue: 93(7), P. 1441 - 1453

Published: Jan. 1, 2024

The nutritional composition and overall quality of maize kernels are largely determined by the key chemical components: protein, oil, starch. Nevertheless, genetic basis underlying these traits during grain filling remains poorly understood. In this study, concentrations starch were studied in 204 recombinant inbred lines resulting from a cross between DH1M T877 at four different stages post-pollination. All exhibited considerable phenotypic variation. During grain-filling stage, levels protein content generally increased, whereas oil decreased, with significant changes observed 30 40 days after pollination. Quantitative trait locus (QTL) mapping was conducted total 32 QTLs, comprising 14, 12, 6 QTLs for detected, respectively. Few consistently detectable across time points. By integrating QTL analysis, global gene expression profiling, comparative genomics, we identified 157, 86, 54 differentially expressed genes harboring nonsynonymous substitutions parental content, Subsequent function annotation prioritized 15 candidate potentially involved regulating traits, including those encoding transcription factors (NAC, MADS-box, bZIP, MYB), cell wall invertase, cellulose-synthase-like division cycle trehalase, auxin-responsive factor, phloem 2-A13. Our study offers insights into architecture kernel identifies promising genes, which crucial enhancement breeding programs.

Language: Английский

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Quantitative genetic models of robustness and evolvability.

Authorea (Authorea), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 28, 2024

Theoretical models of the evolution discrete phenotypes show that most evolvable populations are composed genotypes with intermediate levels phenotypic robustness. This has been attributed to a special kind epistasis, analog which for complex quantitative traits might not readily apparent. Here, simulation models, I variety plausible kinds genetic epistasis will do; as long it increases cryptic diversity and expected allele effect sizes too large. In fact, is necessary, since can also accumulate via plasticity. But plasticity, mapping robustness evolvability sensitive nature predictability environmental variation. So, just discrete-traits, have effects on evolvability, this depends exactly how hidden revealed.

Language: Английский

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