Natural Selection Research Articles

Natural selection on feralization genes contributed to the invasive spread of wild pigs throughout the United States.

Despite a long presence in the contiguous United States (US), the distribution of invasive wild pigs (Sus scrofa × domesticus) has expanded rapidly since the 1980s, suggesting a more recent evolutionary shift towards greater invasiveness. Contemporary populations of wild pigs represent exoferal hybrid descendants of domestic pigs and European wild boar, with such hybridization expected to enrich genetic diversity and increase the adaptive potential of populations. Our objective was to characterize how genetic enrichment through hybridization increases the invasiveness of populations by identifying signals of selection and the ancestral origins of selected loci. Our study focused on invasive wild pigs within Great Smoky Mountains National Park, which represents a hybrid population descendent from the admixture of established populations of feral pigs and an introduction of European wild boar to North America. Accordingly, we genotyped 881 wild pigs with multiple high-density single-nucleotide polymorphism (SNP) arrays. We found 233 markers under putative selection spread over 79 regions across 16 out of 18 autosomes, which contained genes involved in traits affecting feralization. Among these, genes were found to be related to skull formation and neurogenesis, with two genes, TYRP1 and TYR, also encoding for crucial melanogenesis enzymes. The most common haplotypes associated with regions under selection for the Great Smoky Mountains population were also common among other populations throughout the region, indicating a key role of putatively selective variants in the fitness of invasive populations. Interestingly, many of these haplotypes were absent among European wild boar reference genotypes, indicating feralization through genetic adaptation.

Major chromosome rearrangements in intergeneric wheat × rye hybrids in compatible and incompatible crosses detected by GBS read coverage analysis

The presence of incompatibility alleles in primary amphidiploids constitutes a reproductive barrier in newly synthesized wheat-rye hybrids. To overcome this barrier, the genome stabilization process includes large-scale chromosome rearrangements. In incompatible crosses resulting in fertile amphidiploids, the elimination of one of the incompatible alleles Eml-A1 or Eml-R1b can occur already in the somatic tissue of the wheat × rye hybrid embryo. We observed that the interaction of incompatible loci Eml-A1 of wheat and Eml-R1b of rye after overcoming embryo lethality leads to hybrid sterility in primary triticale. During subsequent seed reproductions (R1, R2 or R3) most of the chromosomes of A, B, D and R subgenomes undergo rearrangement or eliminations to increase the fertility of the amphidiploid by natural selection. Genotyping-by-sequencing (GBS) coverage analysis showed that improved fertility is associated with the elimination of entire and partial chromosomes carrying factors that either cause the disruption of plant development in hybrid plants or lead to the restoration of the euploid number of chromosomes (2n = 56) in the absence of one of the incompatible alleles. Highly fertile offspring obtained in compatible and incompatible crosses can be successfully adapted for the production of triticale pre-breeding stocks.

Larger spleens and greater splenic contraction during exercise may be an adaptive characteristic of Nepali Sherpa at high-altitude.

The Sherpa ethnic group living at altitude in Nepal may have experienced natural selection in response to chronic hypoxia. We have previously shown that Sherpa in Kathmandu (1400 m) possess larger spleens and a greater apnea-induced splenic contraction compared to lowland Nepalis. This may be significant for exercise capacity at altitude as the human spleen responds to stress-induced catecholamine secretion by an immediate contraction, which results in transiently elevated hemoglobin concentration ([Hb]). To investigate splenic contraction in response to exercise at high-altitude (4300 m; Pb = ~450 Torr), we recruited 63 acclimatized Sherpa (29F) and 14 Nepali non-Sherpa (7F). Spleen volume was measured before and after maximal exercise on a cycle ergometer by ultrasonography, along with [Hb] and oxygen saturation (SpO2). Resting spleen volume was larger in the Sherpa compared with Nepali non-Sherpa (237 ± 62 vs. 165 ± 34 mL, p < .001), as was the exercise-induced splenic contraction (Δspleen volume, 91 ± 40 vs. 38 ± 32 mL, p < .001). From rest to exercise, [Hb] increased (1.2 to 1.4 g.dl-1), SpO2 decreased (~9%) and calculated arterial oxygen content (CaO2) remained stable, but there were no significant differences between groups. In Sherpa, both resting spleen volume and the Δspleen volume were modest positive predictors of the change (Δ) in [Hb] and CaO2 with exercise (p-values from .026 to .037 and R2 values from 0.059 to 0.067 for the predictor variable). Larger spleens and greater splenic contraction may be an adaptive characteristic of Nepali Sherpa to increase CaO2 during exercise at altitude, but the direct link between spleen size/function and hypoxia tolerance remains unclear.

Selection drives divergence of eye morphology in sympatric Heliconius butterflies.

When populations experience different sensory conditions, natural selection may favor sensory system divergence, affecting peripheral structures and/or downstream neural pathways. We characterized the outer eye morphology of sympatric Heliconius species from different forest types and their first-generation reciprocal hybrids to test for adaptive visual system divergence and hybrid disruption. In Panama, Heliconius cydno occurs in closed forests, whereas Heliconius melpomene resides at the forest edge. Among wild individuals, H. cydno has larger eyes than H. melpomene, and there are heritable, habitat-associated differences in the visual brain structures that exceed neutral divergence expectations. Notably, hybrids have intermediate neural phenotypes, suggesting disruption. To test for similar effects in the visual periphery, we reared both species and their hybrids in common garden conditions. We confirm that H. cydno has larger eyes and provide new evidence that this is driven by selection. Hybrid eye morphology is more H. melpomene-like despite body size being intermediate, contrasting with neural trait intermediacy. Overall, our results suggest that eye morphology differences between H. cydno and H. melpomene are adaptive, and that hybrids may suffer fitness costs due to a mismatch between the peripheral visual structures and previously described neural traits that could affect visual performance.

Insertion-deletions are depleted in protein regions with predicted secondary structure.

A fundamental goal in evolutionary biology and population genetics is to understand how selection shapes the fate of new mutations. Here we test the null hypothesis that insertion-deletion events (indels) in protein coding regions occur randomly with respect to secondary structures. We identified indels across 11,444 sequence alignments in mouse, rat, human, chimp, and dog genomes, then quantified their overlap with four different types of secondary structure - alpha helices, beta strands, protein bends, and protein turns - predicted by deep-learning methods of AlphaFold2. Indels overlapped secondary structures 54% as much as expected, and were especially under-represented over beta strands, which tend to form internal, stable regions of proteins. In contrast, indels were enriched by 155% over regions without any predicted secondary structures. These skews were stronger in the rodent lineages compared to the primate lineages, consistent with population genetic theory predicting that natural selection will be more efficient in species with larger effective population sizes. Nonsynonymous substitutions were also less common in regions of protein secondary structure, although not as strongly reduced as in indels. In a complementary analysis of thousands of human genomes, we showed that indels overlapping secondary structure segregated at significantly lower frequency than indels outside of secondary structure. Taken together, our study shows that indels are selected against if they overlap secondary structure, presumably because they disrupt the tertiary structure and function of a protein.

Wie erlebt man die Evolution? Kulturelle Evolution als Lebenserfahrung

AbstractThe evolution of human culture continues to divide social and biological science. Key issues for both sides are the complexity and variability of culture, the frequency of cultural traits that have no adaptive or functional value, and the apparent exceptionality of human creativity and rationality. This article argues that an examination of how evolution affects the lifetime experience of evolution can reconcile these features of human culture with Darwin’s contention that natural and cultural selection follow the same process of evolution. The article offers a new paradigm that focuses on the relationship between uncertainty and choice in human cultural evolution.

Chemotherapy-induced PTEN-L secretion promotes the selection of PTEN-deficient tumor cells

BackgroundPTEN loss has been identified in various tumor types and is linked to unfavorable clinical outcomes. In addition to PTEN mutation, multiple mechanisms contribute to PTEN loss during tumor development. However, the natural selection process of PTEN-deficient tumor cells remains unclear. Here, we aimed at further elucidating the role of PTEN-L in tumor progression.MethodsPTEN knockout cell lines were generated using CRISPR/Cas9 technology. Ni-NTA affinity column chromatography was employed for PTEN-L purification. Tumor cell metastasis was evaluated in murine models and observed using the IVIS Spectrum Imaging System. RNA-sequencing, western blotting, PCR, flow cytometry, and cell proliferation assays were employed to investigate tumor cell dormancy and related mechanisms.ResultsThe chemotherapeutic drugs, cisplatin, paclitaxel, and doxorubicin, induced tumor cells to secrete PTEN-long (PTEN-L), which shields PTEN-deficient tumor cells from chemotherapy-induced apoptosis better than it shields PTEN-intact cells. Further investigation revealed that PTEN-L treatment induced dormancy in PTEN-null tumor cells, characterized by an increase in p16 and p27 levels, cell-cycle arrest, reduced cell proliferation, and enhanced DNA repair. Furthermore, PTEN-L treatment selectively promoted the accumulation and growth of PTEN-null tumor cells in the lungs of C57BL/6J mice, while evading immune surveillance. Mechanistically, PTEN-L induced dormancy in PTEN-null tumor cells by activating the p38 signaling pathway. Addition of a p38 inhibitor effectively reversed dormancy and growth of PTEN-deficient tumor cells in the lungs. We also demonstrated that PTEN expression played a pivotal role in determining the outcome of PTEN-L-mediated antitumor therapy.ConclusionsIn summary, PTEN-L was identified as a potent inducer of dormancy in PTEN-deficient tumor cells, which increased their efficient selection within the tumor microenvironment.

Comparative Study on Codon Usage Patterns across Chloroplast Genomes of Eighteen Taraxacum Species

This study investigates codon usage bias within the chloroplast genomes of 18 Taraxacum species, focusing on the base composition and various metrics including GC content, Relative Synonymous Codon Usage (RSCU), Effective Number of Codons (ENc), and GC3s. Our analysis revealed a pronounced preference for A/T-ending codons across Taraxacum species, with GC content across the first, second, and third positions of the codons (GC1, GC2, GC3) and the average GC content consistently below 50%. A detailed examination using the RSCU metric identified 29 commonly preferred A/T-ending codons, indicating a strong codon usage bias towards these endings. Specifically, the codon for leucine (UUA) emerged as highly preferred, while the codon for serine (AGC) was least favored. Through the ENc–GC3s plot analysis, we explored the forces shaping this bias, finding evidence that both mutation pressure and natural selection significantly influence codon preference, with most coding sequences showing weak bias. The PR2 plot analysis further confirmed the role of these factors by demonstrating a higher frequency of T over A and C over G at the third codon position, pointing towards a mutation bias complemented by natural selection. Collectively, our findings highlight a consistent pattern of codon usage bias in the chloroplast genomes of Taraxacum species, influenced by a combination of mutation pressure, natural selection, and possibly other unidentified factors.

Insertion of short L1 sequences generates inter-strain histone acetylation differences in the mouse

BackgroundGene expression divergence between populations and between individuals can emerge from genetic variations within the genes and/or in the cis regulatory elements. Since epigenetic modifications regulate gene expression, it is conceivable that epigenetic variations in cis regulatory elements can also be a source of gene expression divergence.ResultsIn this study, we compared histone acetylation (namely, H3K9ac) profiles in two mouse strains of different subspecies origin, C57BL/6 J (B6) and MSM/Ms (MSM), as well as their F1 hybrids. This identified 319 regions of strain-specific acetylation, about half of which were observed between the alleles of F1 hybrids. While the allele-specific presence of the interferon regulatory factor 3 (IRF3) binding sequence was associated with allele-specific histone acetylation, we also revealed that B6-specific insertions of a short 3′ fragment of LINE-1 (L1) retrotransposon occur within or proximal to MSM-specific acetylated regions. Furthermore, even in hyperacetylated domains, flanking regions of non-polymorphic 3′ L1 fragments were hypoacetylated, suggesting a general activity of the 3′ L1 fragment to induce hypoacetylation. Indeed, we confirmed the binding of the 3′ region of L1 by three Krüppel-associated box domain-containing zinc finger proteins (KZFPs), which interact with histone deacetylases. These results suggest that even a short insertion of L1 would be excluded from gene- and acetylation-rich regions by natural selection. Finally, mRNA-seq analysis for F1 hybrids was carried out, which disclosed a link between allele-specific promoter/enhancer acetylation and gene expression.ConclusionsThis study disclosed a number of genetic changes that have changed the histone acetylation levels during the evolution of mouse subspecies, a part of which is associated with gene expression changes. Insertions of even a very short L1 fragment can decrease the acetylation level in their neighboring regions and thereby have been counter-selected in gene-rich regions, which may explain a long-standing mystery of discrete genomic distribution of LINEs and SINEs.

Copy number variation and elevated genetic diversity at immune trait loci in Atlantic and Pacific herring

BackgroundGenome-wide comparisons of populations are widely used to explore the patterns of nucleotide diversity and sequence divergence to provide knowledge on how natural selection and genetic drift affect the genome. In this study we have compared whole-genome sequencing data from Atlantic and Pacific herring, two sister species that diverged about 2 million years ago, to explore the pattern of genetic differentiation between the two species.ResultsThe genome comparison of the two species revealed high genome-wide differentiation but with islands of remarkably low genetic differentiation, as measured by an FST analysis. However, the low FST observed in these islands is not caused by low interspecies sequence divergence (dxy) but rather by exceptionally high estimated intraspecies nucleotide diversity (π). These regions of low differentiation and elevated nucleotide diversity, termed high-diversity regions in this study, are not enriched for repeats but are highly enriched for immune-related genes. This enrichment includes genes from both the adaptive immune system, such as immunoglobulin, T-cell receptor and major histocompatibility complex genes, as well as a substantial number of genes with a role in the innate immune system, e.g. novel immune-type receptor, tripartite motif and tumor necrosis factor receptor genes. Analysis of long-read based assemblies from two Atlantic herring individuals revealed extensive copy number variation in these genomic regions, indicating that the elevated intraspecies nucleotide diversities were partially due to the cross-mapping of short reads.ConclusionsThis study demonstrates that copy number variation is a characteristic feature of immune trait loci in herring. Another important implication is that these loci are blind spots in classical genome-wide screens for genetic differentiation using short-read data, not only in herring, likely also in other species harboring qualitatively similar variation at immune trait loci. These loci stood out in this study because of the relatively high genome-wide baseline for FST values between Atlantic and Pacific herring.

Enhancing Ethiopian power distribution with novel hybrid renewable energy systems for sustainable reliability and cost efficiency

Economic development relies on access to electrical energy, which is crucial for society’s growth. However, power shortages are challenging due to non-renewable energy depletion, unregulated use, and a lack of new energy sources. Ethiopia’s Debre Markos distribution network experiences over 800 h of power outages annually, causing financial losses and resource waste on diesel generators (DGs) for backup use. To tackle these concerns, the present study suggests a hybrid power generation system, which combines solar and biogas resources, and integrates Superconducting Magnetic Energy Storage (SMES) and Pumped Hydro Energy Storage (PHES) technologies into the system. The study also thoroughly analyzes the current and anticipated demand connected to the distribution network using a backward/forward sweep load flow analysis method. The results indicate that the total power loss has reached its absolute maximum, and the voltage profiles of the networks have dropped below the minimal numerical values recommended by the Institute of Electrical and Electronics Engineers (IEEE) standards (i.e., 0.95–1.025 p.u.). After reviewing the current distribution network’s operation, additional steps were taken to improve its effectiveness, using metaheuristic optimization techniques to account for various objective functions and constraints. In the results section, it is demonstrated that the whale optimization algorithm (WOA) outperforms other metaheuristic optimization techniques across three important objective functions: financial, reliability, and greenhouse gas (GHG) emissions. This comparison is based on the capability of the natural selection whale optimization algorithm (NSWOA) to achieve the best possible values for four significant metrics: Cost of Energy (COE), Net Present Cost (NPC), Loss of Power Supply Probability (LPSP), and GHG Emissions. The NSWOA achieved optimal values for these metrics, namely 0.0812 €/kWh, 3.0017 × 106 €, 0.00875, and 7.3679 × 106 kg reduced, respectively. This is attributable to their thorough economic, reliability, and environmental evaluation. Finally, the forward/backward sweep load flow analysis employed during the proposed system’s integration significantly reduced the impact of new energy resources on the distribution network. This was evident in the reduction of total power losses from 470.78 to 18.54 kW and voltage deviation from 6.95 to 0.35 p.u., as well as the voltage profile of the distribution system being swung between 1 and 1.0234 p.u., which now comply with the standards set by the IEEE. Besides, a comparison of the cost and GHG emission efficiency of the proposed hybrid system with existing (grid + DGs) and alternative (only DGs) scenarios was done. The findings showed that, among the scenarios examined, the proposed system is the most economical and produces the least amount of GHG emissions.

Intraspecific and interspecific variations in the synonymous codon usage in mitochondrial genomes of 8 pleurotus strains

In this study, we investigated the codon bias of twelve mitochondrial core protein coding genes (PCGs) in eight Pleurotus strains, two of which are from the same species. The results revealed that the codons of all Pleurotus strains had a preference for ending in A/T. Furthermore, the correlation between codon base compositions and codon adaptation index (CAI), codon bias index (CBI) and frequency of optimal codons (FOP) indices was also detected, implying the influence of base composition on codon bias. The two P. ostreatus species were found to have differences in various base bias indicators. The average effective number of codons (ENC) of mitochondrial core PCGs of Pleurotus was found to be less than 35, indicating strong codon preference of mitochondrial core PCGs of Pleurotus. The neutrality plot analysis and PR2-Bias plot analysis further suggested that natural selection plays an important role in Pleurotus codon bias. Additionally, six to ten optimal codons (ΔRSCU > 0.08 and RSCU > 1) were identified in eight Pleurotus strains, with UGU and ACU being the most widely used optimal codons in Pleurotus. Finally, based on the combined mitochondrial sequence and RSCU value, the genetic relationship between different Pleurotus strains was deduced, showing large variations between them. This research has improved our understanding of synonymous codon usage characteristics and evolution of this important fungal group.

Feature selection algorithm based on optimized genetic algorithm and the application in high-dimensional data processing

High-dimensional data is widely used in many fields, but selecting key features from it is challenging. Feature selection can reduce data dimensionality and weaken noise interference, thereby improving model efficiency and enhancing model interpretability. In order to improve the efficiency and accuracy of high-dimensional data processing, a feature selection method based on optimized genetic algorithm is proposed in this study. The algorithm simulates the process of natural selection, searches for possible subsets of feature, and finds the subsets of feature that optimizes the performance of the model. The results show that when the value of K is less than 4 or more than 8, the recognition rate is very low. After adaptive bias filtering, 724 features are filtered to 372, and the accuracy is improved from 0.9352 to 0.9815. From 714 features to 406 Gaussian codes, the accuracy is improved from 0.9625 to 0.9754. Among all tests, the colon has the highest average accuracy, followed by small round blue cell tumor(SRBCT), lymphoma, central nervous system(CNS) and ovaries. The green curve is the best, with stable performance and a time range of 0–300. While maintaining the efficiency, it can reach 4.48 as soon as possible. The feature selection method has practical significance for high-dimensional data processing, improves the efficiency and accuracy of data processing, and provides an effective new method for high-dimensional data processing.

Digest: When sexual selection hits the wall of natural selection.

Sexual selection often drives traits in a direction that is disfavored by natural selection. The balance between these two types of selection can shift rapidly in response to environmental changes. Gallagher et al. (2024) report such a shift in a cricket population following the introduction of a parasitoid fly. The ancestral male morph, though still preferred by females, has been supplanted by multiple novel morphs that are more difficult for the parasitoid to detect.

Mutational robustness and the role of buffer genes in evolvability.

Organisms rely on mutations to fuel adaptive evolution. However, many mutations impose a negative effect on fitness. Cells may have therefore evolved mechanisms that affect the phenotypic effects of mutations, thus conferring mutational robustness. Specifically, so-called buffer genes are hypothesized to interact directly or indirectly with genetic variation and reduce its effect on fitness. Environmental or genetic perturbations can change the interaction between buffer genes and genetic variation, thereby unmasking the genetic variation's phenotypic effects and thus providing a source of variation for natural selection to act on. This review provides an overview of our understanding of mutational robustness and buffer genes, with the chaperone gene HSP90 as a key example. It discusses whether buffer genes merely affect standing variation or also interact with de novo mutations, how mutational robustness could influence evolution, and whether mutational robustness might be an evolved trait or rather a mere side-effect of complex genetic interactions.

Biology, phylogenetic and evolutionary relations of Tradescantia mild mosaic virus isolates from Hungary

Biology, phylogenetic and evolutionary relations of Tradescantia mild mosaic virus isolates from Hungary

Selection of Words in Ontogeny

AbstractThis article suggests a framework for integrating a conceptual and an empirical approach to understanding human speech. Verbal activities may be understood as a result of conjoint phylogenetic and ontogenetic selection processes. The present article situates an experimental procedure investigating verbal activities as a function of ontogenetic events in the larger context of Darwinian selection. In this experimental procedure, the experimenter uttered “hmm” and “yes” contingently and contiguously on a participant’s mentioning of predefined words. To test if the experimenter’s verbal activity modified the participant’s rate of those words, 63 Norwegian participants reported individually on video recordings. Resembling the results of previous studies, cumulative relative frequency distributions of target word rates showed that three of four target words occurred at a higher rate when the experimenter uttered “hmm” and “yes” during a participant’s report than when she was silent. Methodological challenges of investigating the selection of verbal activities by their contingencies with Phylogenetically Important Events are discussed.

Social interactions generate complex selection patterns in virtual worlds.

Understanding the influence of social interactions on individual fitness is key to improving our predictions of phenotypic evolution. However, we often overlook the different components of selection regimes arising from interactions among organisms, including social, correlational, and indirect selection. This is due to the challenging sampling efforts required in natural populations to measure phenotypes expressed during interactions and individual fitness. Furthermore, behaviours are crucial in mediating social interactions, yet few studies have explicitly quantified these selection components on behavioural traits. In this study, we capitalize on an online multiplayer videogame as a source of extensive data recording direct social interactions among prey, where prey collaborate to escape a predator in realistic ecological settings. We estimate natural and social selection and their contribution to total selection on behavioural traits mediating competition, cooperation, and predator-prey interactions. Behaviours of other prey in a group impact an individual's survival, and thus are under social selection. Depending on whether selection pressures on behaviours are synergistic or conflicting, social interactions enhance or mitigate the strength of natural selection, although natural selection remains the main driving force. Indirect selection through correlations among traits also contributed to the total selection. Thus, failing to account for the effects of social interactions and indirect selection would lead to a misestimation of the total selection acting on traits. Dissecting the contribution of each component to the total selection differential allowed us to investigate the causal mechanisms relating behaviour to fitness and quantify the importance of the behaviours of conspecifics as agents of selection. Our study emphasizes that social interactions generate complex selective regimes even in a relatively simple ecological environment.

Meiotic drive against chromosome fusions in butterfly hybrids

Species frequently differ in the number and structure of chromosomes they harbor, but individuals that are heterozygous for chromosomal rearrangements may suffer from reduced fitness. Chromosomal rearrangements like fissions and fusions can hence serve as a mechanism for speciation between incipient lineages, but their evolution poses a paradox. How can rearrangements get fixed between populations if heterozygotes have reduced fitness? One solution is that this process predominantly occurs in small and isolated populations, where genetic drift can override natural selection. However, fixation is also more likely if a novel rearrangement is favored by a transmission bias, such as meiotic drive. Here, we investigate chromosomal transmission distortion in hybrids between two wood white (Leptidea sinapis) butterfly populations with extensive karyotype differences. Using data from two different crossing experiments, we uncover that there is a transmission bias favoring the ancestral chromosomal state for derived fusions, a result that shows that chromosome fusions actually can fix in populations despite being counteracted by meiotic drive. This means that meiotic drive not only can promote runaway chromosome number evolution and speciation, but also that it can be a conservative force acting against karyotypic change and the evolution of reproductive isolation. Based on our results, we suggest a mechanistic model for why chromosome fusion mutations may be opposed by meiotic drive and discuss factors contributing to karyotype evolution in Lepidoptera.

Flow-geomechanics coupling constrains fault geometry in induced earthquakes

Post-mortem analysis of earthquakes induced by fluid extraction or injection is often complicated by the uncertainty in the location and geometry of the causative fault. The 2011 Lorca earthquake in southeast Spain is believed to have been triggered by long-term groundwater withdrawal, causing slip along the Alhama de Murcia Fault (AMF) dipping northwest. However, the regional InSAR deformation data can be equally fit by AMF and an unmapped fault located approximately 5-8 km west of AMF and dipping southeast, which creates an ambiguity in the causative fault that hosted the earthquake. Here, we show that the assumptions of elastic dislocation, undrained deformation, and decoupling between flow and deformation processes contributed to the ambiguity, which can be resolved by conducting a fully coupled analysis that provides additional constraints on the problem. We test that hypothesis and propose that the Lorca earthquake was likely caused by the rupture of a southeast dipping fault plane, which is antithetic to AMF. We build a mechanistic model of groundwater withdrawal over the time period of interest (1960–2010) that includes pressure diffusion, aquifer contraction, crustal unloading, and basement expansion mechanisms. The model identifies the difference in production-induced loading of the two faults: AMF experiences poroelastic compression and down-dip shear whereas the antithetic fault experiences tension and up-dip shear. We demonstrate that two-way coupling between flow and deformation processes plays a crucial role in the natural selection of the causative fault. The proposed framework holds the potential to detect hidden faults capable of hosting earthquakes.