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Cost of Altered Translation Accuracy Shapes Adaptation to Antibiotics in E. coli. 翻译准确性改变的代价影响了大肠杆菌对抗生素的适应。
IF 5.3 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-28 DOI: 10.1093/molbev/msaf312
Laasya Samhita, Sharvari Tamhankar, Joshua Miranda, Aabeer Basu, Deepa Agashe

Protein synthesis, while central to cellular function, is error-prone. The resulting mistranslation is generally costly, but we do not know how these costs compare or interact with the costs imposed by external selection pressures such as antibiotics. We also do not know whether and how these costs are compensated during evolution. It is important to answer these questions, since mistranslation is ubiquitous and antibiotic exposure is widespread. We quantified the growth cost of genetically increasing and decreasing mistranslation rates and exposure to low antibiotic concentrations in Escherichia coli. Mistranslation costs were generally lower than the cost imposed by antibiotics and exacerbated in a strain-specific manner under antibiotic exposure. All strains quickly compensated for the antibiotic cost during experimental evolution, via antibiotic- and genotype- specific mutations. In contrast, mistranslation costs were significantly reduced only in some cases, without clear causal mutations. Control populations that evolved without antibiotics consistently compensated for the cost of accuracy and evolved increased antibiotic resistance as a by-product. Our work demonstrates that even when the cost of mistranslation is weak, altered translation accuracy can shape adaptive outcomes and underlying genetic mechanisms, with strong collateral fitness effects for apparently unrelated phenotypes such as antibiotic resistance.

蛋白质合成虽然对细胞功能至关重要,但却容易出错。由此产生的错误翻译通常是昂贵的,但我们不知道这些成本如何与外部选择压力(如抗生素)所施加的成本进行比较或相互作用。我们也不知道这些代价是否以及如何在进化过程中得到补偿。回答这些问题很重要,因为误译是普遍存在的,抗生素暴露是普遍存在的。我们量化了在大肠杆菌中遗传增加和减少误翻译率和暴露于低抗生素浓度的生长成本。误译成本通常低于抗生素造成的成本,并且在抗生素暴露下以菌株特异性的方式加剧。在实验进化过程中,所有菌株都通过抗生素和基因型特异性突变迅速补偿了抗生素的成本。相比之下,只有在某些情况下,没有明确的因果突变,误译成本才会显著降低。在没有抗生素的情况下进化的控制种群不断补偿准确性的成本,并作为副产品进化出增加的抗生素耐药性。我们的工作表明,即使误译的成本很低,翻译准确性的改变也会影响适应性结果和潜在的遗传机制,对明显不相关的表型(如抗生素耐药性)具有很强的附带适应度效应。
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引用次数: 0
Comprehensive Annotation of Olfactory and Gustatory Receptor Genes and Transposable Elements Revealed Their Evolutionary Dynamics in Aphids. 对蚜虫嗅觉和味觉受体基因及其转座因子的综合注释揭示了它们的进化动态。
IF 5.3 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-28 DOI: 10.1093/molbev/msaf238
Sergio Gabriel Olvera-Vazquez, Xilong Chen, Aurélie Mesnil, Camille Meslin, Fabricio Almeida-Silva, Johann Confais, Yann Bourgeois, Gianluca Lombardi, Célia Lougmani, Karine Alix, Nicolas Francillonne, Nathalie Choisne, Stephane Cauet, Jean-Christophe Simon, Christelle Buchard, Nathalie Rodde, David Ogereau, Claire Mottet, Alexandre Degrave, Elorri Segura, Alessandra Carbone, Barrès Benoit, Emmanuelle Jacquin-Joly, William Marande, Dominique Lavenier, Fabrice Legeai, Amandine Cornille

Gene duplication and transposable elements (TEs) are major drivers of genomic innovation that can fuel adaptation. While the roles of duplication and TE-driven diversification are documented in plant pathogens, they remain insufficiently explored in insect pests such as aphids, where olfactory (OR) and gustatory receptor (GR) genes are key to host recognition. We analyzed 521 OR and 399 GR genes, alongside TEs, across 12 aphid genomes with varying host ranges. Aphid lineages with broader host ranges exhibited higher evolutionary rates, driven by gene family expansions linked to host interaction, including lipid metabolism, immune function, and transposase activity. OR and GR genes evolved through proximal and tandem duplications and were shaped by diversifying selection, with bursts of positive selection followed by prolonged purifying selection, consistent with adaptation to novel hosts. Younger TEs were significantly enriched near OR genes compared to GRs and other genomic regions, suggesting a catalytic role of TEs in their diversification. However, OR proteins encoded by TE-associated ORs exhibited reduced functional potential. In contrast, GR proteins encoded by TE-associated GRs retained signatures of adaptation, as inferred from deep learning models predicting functionally important protein regions. These findings suggest that TE activity may facilitate functional innovation in GRs while alleviating constraints or pseudogenization in ORs. This study reveals how duplication, selection, and TE dynamics shape gene evolution in insect pests. It also provides the first chromosome-scale genome assembly of Dysaphis plantaginea, with comprehensive annotations and functional predictions of OR/GR genes, bridging adaptive evolution with mechanistic insights.

基因复制和转座因子(te)是基因组创新的主要驱动力,可以促进适应。虽然复制和te驱动的多样化在植物病原体中的作用已被记录,但它们在蚜虫等害虫中的作用仍未得到充分探索,其中嗅觉(OR)和味觉受体(GR)基因是宿主识别的关键。我们分析了12个不同寄主范围的蚜虫基因组中的521个OR基因和399个GR基因以及te基因。寄主范围更广的蚜虫谱系表现出更高的进化速度,这是由与寄主相互作用相关的基因家族扩展所驱动的,包括脂质代谢、免疫功能和转座酶活性。OR和GR基因是通过近端和串联复制进化而来的,并通过多样化选择形成,先是爆发积极选择,然后是长时间的净化选择,与对新宿主的适应一致。与GRs和其他基因组区域相比,较年轻的te在OR基因附近显著富集,表明te在其多样化中起着催化作用。然而,te相关OR编码的OR蛋白表现出降低的功能电位。相比之下,由te相关GR编码的GR蛋白保留了适应特征,这是从预测功能重要蛋白区域的深度学习模型推断出来的。这些发现表明,TE活动可能促进GRs的功能创新,同时减轻ORs的限制或假性。本研究揭示了复制、选择和TE动力学如何影响害虫的基因进化。它还提供了车前草(Dysaphis plantaginea)第一个染色体尺度的基因组组装,对OR/GR基因进行了全面的注释和功能预测,将适应进化与机制见解联系起来。
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引用次数: 0
SAI: A Python Package for Statistics for Adaptive Introgression. SAI:一个用于自适应渗透统计的Python包。
IF 5.3 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-28 DOI: 10.1093/molbev/msaf295
Xin Huang, Simon Chen, Josef Hackl, Martin Kuhlwilm

Adaptive introgression is an important evolutionary process, which can be identified with widely used summary statistics, such as the number of uniquely shared sites and the quantile of the derived allele frequencies in such sites. However, these as well as more recently developed statistics such as D+ and Danc, still lack accessible implementations. Here, we present SAI, a Python package for computing these statistics along with a new statistic, DD, and demonstrate its application on 2 datasets. First, using the 1000 Genomes Project data, we replicated previously reported candidate regions and identified additional ones, including a region detected by studies using supervised deep learning. Second, we investigated bonobo introgression into central chimpanzees and identified candidate genes, finding one region that overlaps a high-frequency Denisovan-introgressed haplotype block reported in modern Papuans. This is an intriguing co-occurrence across divergent lineages, underscoring the role of adaptive introgression in evolution.

自适应渐渗是一个重要的进化过程,可以通过广泛使用的汇总统计来识别,例如唯一共享位点的数量和这些位点中衍生等位基因频率的分位数。然而,这些以及最近开发的统计数据(如D+和Danc)仍然缺乏可访问的实现。在这里,我们介绍了用于计算这些统计数据的Python包SAI和一个新的统计数据DD,并演示了它在两个数据集上的应用。首先,利用1000基因组计划的数据,我们复制了之前报道的候选区域,并确定了额外的区域,包括使用监督深度学习研究检测到的区域。其次,我们研究了倭黑猩猩向中心黑猩猩的基因渗入,并确定了候选基因,发现一个区域与现代巴布亚人中报道的高频丹尼索瓦人基因渗入单倍型片段重叠。这是一种在不同谱系中有趣的共同现象,强调了适应性渐渗在进化中的作用。
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引用次数: 0
Life Cycle Simplifications in Aphids Drive Changes in Evolutionary Rates and Selection Regimes. 蚜虫生命周期的简化推动了进化速率和选择机制的变化。
IF 5.3 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-28 DOI: 10.1093/molbev/msaf307
Théo Vericel, Gaorui Gong, Fabrice Legeai, Aurélie Etier, Julie Jaquiéry, Jean-Christophe Simon

Transitions toward simplified life cycles can reshape evolutionary trajectories, yet their impact on the rate of molecular evolution remains poorly understood. In aphids, host alternation (heteroecy) entails obligate seasonal migration between highly distinct plant hosts-typically woody and herbaceous species-and has been repeatedly lost, giving rise to monoecious species with simplified life cycles. Using comparative genomics across 46 aphid species, we tested whether transitions from heteroecy to monoecy alter evolutionary dynamics at the gene level. We identified 9,304 orthologs and estimated evolutionary rates (dN/dS) and shifts in selection regimes in the diverse Aphidinae subfamily. We found that 715 orthologs evolved faster in monoecious species, primarily due to relaxed selection, while heteroecious species showed signatures of intensified selection. Genes under relaxed selection in monoecious species were enriched for functions related to environmental sensing, signaling, nutritional adjustments, morph determination, and migration related-traits likely central for host alternation. These results suggest that the loss of a complex life cycle leads to reduced selective constraints as a consequence of ecological simplification. This study provides a robust evolutionary framework for understanding how life cycle transitions shape molecular evolution and drive gene decay following trait loss.

向简化生命周期的过渡可以重塑进化轨迹,但它们对分子进化速度的影响仍然知之甚少。在蚜虫中,寄主交替(杂种)需要在高度不同的植物寄主(通常是木本植物和草本植物)之间进行季节性迁移,并且已经反复丢失,从而产生具有简化生命周期的雌雄同株物种。利用46种蚜虫的比较基因组学,我们测试了从杂种到单性的转变是否会在基因水平上改变进化动力学。我们确定了9304个直系同源,并估计了不同蚜虫亚科的进化速率(dN/dS)和选择机制的变化。结果表明,715种同系物在雌雄同株物种中进化较快,主要是由于选择的放松,而异种物种则表现出强化选择的特征。在雌雄同株中,放松选择的基因丰富了与环境感知、信号传导、营养调节、形态决定和迁移相关的功能,这些功能可能是寄主交替的核心特征。这些结果表明,由于生态简化,复杂生命周期的丧失导致选择约束的减少。这项研究为理解生命周期转变如何影响分子进化和驱动性状丧失后的基因衰变提供了一个强大的进化框架。
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引用次数: 0
Genomic Signatures of Selection Across Climate Gradients and a Geographic Mosaic of Coevolution in an Ant Social Parasite-Host System. 跨气候梯度选择的基因组特征和蚂蚁社会寄生虫-宿主系统协同进化的地理马赛克。
IF 5.3 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-28 DOI: 10.1093/molbev/msaf293
Maide Nesibe Macit, Erwann Collin, Maria Esther Nieto-Blazquez, Marion Kever, Maria Litto, Esther Jaitner, Markus Pfenninger, Barbara Feldmeyer, Susanne Foitzik

Coevolutionary dynamics in host-parasite systems are shaped by reciprocal selection and environmental context. When hosts and parasites share ancestry and ecological overlap, selection can act on similar traits, but population structure and geography may generate adaptive mosaics. Here, we present the first study to investigate genome-wide signatures of selection in response to a broad climatic gradient and a geographic mosaic of coevolution between a social parasite and its host. We examined these processes in the dulotic ant Temnothorax americanus and its congeneric host Temnothorax longispinosus using population genomics, genome-wide association analyses, and transcriptomics. Host populations showed very weak and parasites stronger population structure, enabling geographic mosaic dynamics. Genomic responses to parasite prevalence were divergent: Hosts showed signatures of selection on immune genes, whereas regulatory genes associated with raiding were under selection in parasites. Both species displayed convergent signatures of climate adaptation, including loci related to desiccation resistance, stress response, and parasite prevalence, with signals in communication and recognition genes involved in hydrocarbon biosynthesis, chemosensory perception, circadian rhythms, and venom production. Transcriptome analyses revealed contrasting patterns, with host gene expression linked to parasite prevalence and parasite expression more strongly shaped by climate. Together, our results reveal a genomic mosaic of coadaptation, in which population structure, asymmetric selection, and ecological variation interact to generate divergent yet interconnected evolutionary trajectories. Our findings highlight communication and recognition as recurrent arenas of antagonistic coevolution, underscore climate as a pervasive selective force, and establish a framework for investigating molecular coevolution in social parasite systems.

宿主-寄生虫系统的共同进化动力学是由相互选择和环境背景形成的。当寄主和寄生虫有共同的祖先和生态重叠时,选择可以对相似的特征起作用,但种群结构和地理可能产生适应性镶嵌。在这里,我们首次研究了社会性寄生虫与其宿主之间广泛的气候梯度和地理马赛克共同进化的全基因组选择特征。我们利用群体基因组学、全基因组关联分析和转录组学研究了美洲Temnothorax americanus及其同属宿主T. longispinosus的这些过程。寄主种群结构较弱,寄主种群结构较强,形成了地理上的镶嵌动态。对寄生虫流行的基因组反应是不同的:宿主表现出对免疫基因的选择特征,而与袭击相关的调控基因在寄生虫中处于选择状态。这两个物种都显示出气候适应的趋同特征,包括与干燥抗性、应激反应和寄生虫流行相关的位点,以及涉及碳氢化合物生物合成、化学感觉感知、昼夜节律和毒液产生的通信和识别基因的信号。转录组分析揭示了截然不同的模式,宿主基因表达与寄生虫流行率有关,而寄生虫表达受气候影响更大。总之,我们的研究结果揭示了共同适应的基因组马赛克,其中种群结构、不对称选择和生态变异相互作用,产生了不同但又相互联系的进化轨迹。我们的研究结果强调了交流和识别是对抗性共同进化的反复出现的领域,强调了气候是一种普遍的选择力量,并建立了研究社会寄生虫系统中分子共同进化的框架。
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引用次数: 0
Ancestral Sequence Reconstruction Provides Insights into the Structural Diversification and Neofunctionalization of T-superfamily Conotoxins in Conus. 祖先序列重建为圆锥虫t超家族圆锥虫毒素的结构多样化和新功能化提供了新的思路。
IF 5.3 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-28 DOI: 10.1093/molbev/msaf302
Samuel S Espino, Thomas Lund Koch, Joanna Gajewiak, Matías L Giglio, Maren Watkins, Helena Safavi-Hemami, Baldomero M Olivera

Due to their remarkable diversity and rapid evolution, conotoxins-peptide toxins from predatory marine cone snails-provide a powerful system for exploring how gene diversification may contribute to the development of lineage-specific adaptations. We previously demonstrated that 2-loop Tau conotoxins represent an evolutionary innovation associated with mollusk-hunting behaviors in cone snails. Here, we investigate the evolutionary history of these toxins as a model to understand the mechanism of ancestral gene neofunctionalization, which may have contributed to the emergence of mollusk-hunting in cone snails. Using ancestral sequence reconstruction, we present a model in which ancestral T-superfamily conotoxins neofunctionalized into the 2-loop Tau conotoxins. Predicted ancestral sequences reveal an intermediate structure between the classic T-superfamily conotoxins and the derived 2-loop Tau forms. Notably, these ancestral intermediates acquired a new cysteine scaffold that facilitated a structural transition from a globular to a ribbon fold. This conformational shift was followed by sequence-level changes that presumably enhanced activity against molecular targets in mollusks. We propose that the emergence of 2-loop Tau conotoxins may have been one factor that contributed to the emergence of molluscivory, providing insight into how gene innovation may underlie ecological diversification.

由于其显著的多样性和快速的进化,贝壳毒素——来自掠食性海锥蜗牛的肽毒素——为探索基因多样化如何促进谱系特异性适应的发展提供了一个强大的系统。我们之前已经证明,2环Tau conotoxins代表了一种与锥体蜗牛捕食软体动物行为相关的进化创新。在这里,我们研究了这些毒素的进化史,作为一个模型来理解祖先基因新功能化的机制,这可能有助于锥螺捕食软体动物的出现。通过祖先序列重建,我们提出了一个模型,其中祖先t超家族的concontoxin被新功能化为2环Tau concontoxin。预测的祖先序列揭示了经典t超家族conotoxins和衍生的2-loop Tau形式之间的中间结构。值得注意的是,这些祖先的中间产物获得了一个新的半胱氨酸支架,促进了从球状褶皱到带状褶皱的结构转变。这种构象变化之后是序列水平的变化,这可能增强了软体动物对分子靶标的活性。我们提出,2环Tau conotoxins的出现可能是软体动物出现的一个因素,这为基因创新如何成为生态多样化的基础提供了见解。
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引用次数: 0
Sponges, ctenophores, and the statistical significance of syntenies. 海绵、栉水母及其共系的统计意义。
IF 5.3 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-28 DOI: 10.1093/molbev/msaf321
Richard R Copley

Shared fusions between ancestral chromosomal linkage groups have previously been used to support phylogenetic groupings, notably sponges with cnidarians and bilaterians to the exclusion of ctenophores, rendering ctenophores the sister group to all other animals. The linkage groups used to identify these fusions were assessed for statistical significance relative to a model of randomly shuffled genes. I argue that the method of random shuffling treated all species as equally distant from each other and so overestimated the significance of the observed linkages. I calculate alternative statistics and further argue that there are likely to be real linkage groups that are not identified as significant. If linkage groups are not supported statistically, they cannot reliably be used to identify shared derived chromosomal rearrangements, and hence phylogenetic hypotheses derived from them are suspect.

祖先染色体连锁群之间的共同融合先前被用于支持系统发育分组,特别是海绵与刺胞动物和双边动物,而排除了栉水母,使栉水母成为所有其他动物的姐妹群。用于鉴定这些融合的连锁组相对于随机洗牌基因的模型进行了统计显著性评估。我认为,随机洗牌的方法将所有物种视为彼此距离相等,因此高估了观察到的联系的重要性。我计算了其他统计数据,并进一步论证可能存在未被识别为显著的真正联系组。如果连锁群没有统计上的支持,它们就不能可靠地用于识别共同衍生的染色体重排,因此由此衍生的系统发育假说是可疑的。
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引用次数: 0
Whole-Genome Duplication Reshapes Adaptation: Autotetraploid Arabidopsis arenosa Leverages its High Genetic Variation to Compensate for Selection Constraints. 全基因组复制重塑适应性:同源四倍体拟南芥利用其高遗传变异来补偿选择限制。
IF 5.3 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-28 DOI: 10.1093/molbev/msaf298
Sonia Celestini, Veronika Lipánová, Jakub Vlček, Filip Kolář

Whole-genome duplication (WGD), a widespread macromutation across eukaryotes, is predicted to affect the tempo and modes of evolutionary processes. By theory, the additional set(s) of chromosomes present in polyploid organisms may reduce the efficiency of selection while, simultaneously, increasing heterozygosity and buffering deleterious mutations. Despite the theoretical significance of WGD, empirical genomic evidence from natural polyploid populations is scarce and direct comparisons of selection footprints between autopolyploids and closely related diploids remains completely unexplored. We therefore combined locally sampled soil data with resequenced genomes of 76 populations of diploid-autotetraploid Arabidopsis arenosa and tested whether the genomic signatures of adaptation to distinct siliceous and calcareous soils differ between the ploidies. Leveraging multiple independent transitions between these soil types in each ploidy, we identified a set of genes associated with ion transport and homeostasis that were repeatedly selected for across the species' range. Notably, polyploid populations have consistently retained greater variation at candidate loci compared with diploids, reflecting lower fixation rates. In tetraploids, positive selection predominantly acts on such a large pool of standing genetic variation, rather than targeting de novo mutations. Finally, selection in tetraploids targets genes that are more central within the protein-protein interaction network, potentially impacting a greater number of downstream fitness-related traits. In conclusion, both ploidies thrive across a broad gradient of substrate conditions, but WGD fundamentally alters the ploidies adaptive strategies: tetraploids leverage their greater genetic variation and redundancy to compensate for the predicted constraints on the efficacy of positive selection.

全基因组复制(WGD)是一种在真核生物中广泛存在的大突变,预计会影响进化过程的速度和模式。从理论上讲,多倍体生物中存在的额外一组染色体可能会降低选择的效率,同时增加杂合性并缓冲有害突变。尽管WGD具有理论意义,但来自自然多倍体群体的经验基因组证据很少,而且自多倍体和密切相关的二倍体之间的选择足迹的直接比较仍然完全没有探索过。因此,我们将当地采样的土壤数据与76个二倍体-同源四倍体拟南芥群体的基因组测序相结合,测试了不同倍体对不同硅质和钙质土壤的适应基因组特征是否存在差异。利用每个倍性中这些土壤类型之间的多个独立转换,我们确定了一组与离子运输和稳态相关的基因,这些基因在整个物种范围内被反复选择。值得注意的是,与二倍体相比,多倍体群体在候选位点上一直保持着更大的变异,这反映了较低的固定率。在四倍体中,正选择主要作用于如此大的遗传变异库,而不是针对新生突变。最后,四倍体的选择目标是在蛋白质-蛋白质相互作用网络中更为中心的基因,这可能会影响更多的下游适应性相关性状。总之,这两种倍体都能在广泛的底物条件梯度下生长,但WGD从根本上改变了倍体的适应策略:四倍体利用其更大的遗传变异和冗余来补偿对正选择效率的预期限制。
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引用次数: 0
Bayesian Model Averaging of Parametric Coalescent Models for Phylodynamic Inference. 用于系统动力学推断的参数演化模型的贝叶斯模型平均。
IF 5.3 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-28 DOI: 10.1093/molbev/msaf297
Yuan Xu, Kylie Chen, Dong Xie, Alexei J Drummond

Bayesian phylodynamic models have become essential for reconstructing population history from genetic data, yet their accuracy depends crucially on choosing appropriate demographic models. To address uncertainty in model choice, we introduce a Bayesian model averaging (BMA) framework that integrates multiple parametric coalescent models-including constant, exponential, logistic, and Gompertz growth-along with their "expansion" variants that account for non-zero ancestral populations. Implemented in a Bayesian setting with Metropolis-coupled Markov chain Monte Carlo, this approach allows the sampler to switch among candidate growth functions, thereby capturing demographic histories without having to pre-specify a single model. Simulation studies verify that the logistic and Gompertz models may require specialized sampling strategies such as adaptive multivariate proposals to achieve robust mixing. We demonstrate the performance of these models on datasets simulated under different substitution models, and show that joint inference of genealogy and population parameters is well-calibrated when properly incorporating correlated-move operators and BMA. We then apply this method to two real-world datasets. Analysis of Egyptian Hepatitis C virus sequences indicates that models with a founder population followed by a rapid expansion are well supported, with a slight preference for Gompertz-like expansions. Our analysis of a metastatic colorectal cancer single-cell dataset suggests that exponential-like growth is plausible even for an advanced stage cancer patient. We believe this highlights that tumor subclones may retain substantial proliferative capacity into the later stages of the disease. Overall, our unified BMA framework reduces the need for restrictive model selection procedures and can also provide deeper biological insights into epidemic spread and tumor evolution. By systematically integrating multiple growth hypotheses within a standard Bayesian setting, this approach naturally avoids overfitting and offers a powerful tool for inferring population histories across diverse biological domains.

贝叶斯系统动力学模型已经成为从遗传数据重建种群历史的关键,但其准确性关键取决于选择合适的人口统计学模型。为了解决模型选择中的不确定性,我们引入了一个贝叶斯模型平均(BMA)框架,该框架集成了多个参数聚结模型——包括常数、指数、逻辑和Gompertz增长——以及它们的“扩展”变体,这些变体解释了非零祖先种群。该方法在Metropolis-coupled MCMC的贝叶斯设置中实现,允许采样器在候选生长函数之间切换,从而无需预先指定单个模型即可捕获人口统计历史。仿真研究证实,逻辑模型和Gompertz模型可能需要专门的采样策略,如自适应多变量建议,以实现鲁棒混合。我们证明了这些模型在不同替代模型下模拟的数据集上的性能,并表明当适当地结合相关移动算子和BMA时,家谱和总体参数的联合推断可以很好地校准。然后我们将这种方法应用于两个真实世界的数据集。对埃及丙型肝炎病毒(HCV)序列的分析表明,有一个创始者群体然后快速扩张的模型得到了很好的支持,稍微倾向于gompertz样扩张。我们对转移性结直肠癌(CRC)单细胞数据集的分析表明,即使对于晚期癌症患者,指数样生长也是合理的。我们认为,这突出表明肿瘤亚克隆可能在疾病的后期阶段保留大量的增殖能力。总的来说,我们统一的BMA框架减少了对限制性模型选择程序的需求,还可以为流行病传播和肿瘤进化提供更深入的生物学见解。通过在标准贝叶斯设定中系统地整合多个生长假设,该方法自然地避免了过拟合,并为推断不同生物领域的种群历史提供了强大的工具。
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引用次数: 0
SMBE Secretary's Report 2025. 中小企业秘书报告2025。
IF 5.3 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-28 DOI: 10.1093/molbev/msaf280
Emmanuelle Lerat
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Molecular biology and evolution
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