Biology subjects

Saini, S.

Publications and source records attributed to Saini, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Evolutionarily Conserved Plasmodium falciparum HSP70-3 Enhances the Immunogenicity of the Established Malaria Vaccine Antigen Circumsporozoite Protein through Cross-Presentation

Background: Clinically approved P. falciparum circumsporozoite protein (PfCSP)-based pre-erythrocytic stage malaria vaccines suffer from sub-optimal efficacy and rapidly waning memory. By decoding these limitations, we fast-tracked vaccine optimization by correcting CSPs fragile immunogenicity using a parasite-derived chaperone. Unlike other orthologues of P. falciparum heat shock protein 70 (PfHSP70), substrate-binding domain (SBD) of PfHSP70-3 is an evolutionarily conserved internal mitochondrial matrix chaperone. We demonstrate that PfHSP70-3-SBD hydrophobic region complexes with PfCSP and targets host CD91 on antigen-presenting cells to trigger cross-presentation, resulting in enhanced immune responses to PfCSP. Methods: In silico analyses predicted interactions among PfHSP70-3-SBD, PfCSP, and CD91 receptor. Recombinant PfHSP70-3-SBD and PfCSP proteins were purified and assessed for in vitro interaction using ELISA and far-western dot blot assays. BALB/c mice were immunized with alum-formulated PfCSP, with or without PfHSP70-3-SBD. PfCSP-specific IgG and IFN-{gamma} expression were evaluated by ELISA and RT-qPCR, respectively. Functional activity was assessed using transgenic Plasmodium berghei expressing PfCSP (Pb/Pf CSP), by sporozoite neutralization assay. Findings: PfHSP70-3-SBD demonstrated a specific interaction with PfCSP. The complex primarily engages CD91 receptor cluster IV, providing a potential mechanistic basis for antigen cross-presentation. Incorporation of PfHSP70-3-SBD enhanced PfCSP-specific total IgG responses and increased IFN-gamma expression in BALB/c mice, indicating improved immunogenicity upon co-formulation. Notably, immune sera neutralized Pb/Pf CSP sporozoites, delaying blood-stage patency until day 12 in 40% of C57BL/6 mice, with no detectable parasitemia in surviving mice for up to 2 months, indicating sustained efficacy against the sporozoite stage. Interpretation: Molecular chaperones, including HSPs, are currently under intense investigation for their immune-potentiating activity, leading to next-generation vaccine development. By utilizing chaperonic domains derived directly from the pathogenic agent itself to serve an essential adjuvant function, this approach reduces reliance on heterologous adjuvants while enhancing antigen-specific immunity. Funding: This work was supported by funding from Indian Council of Medical Research (IIRPSG-2024-01-03940). Keywords: Substrate-binding domain, PfHSP70-3, Adjuvant, Cross-presentation, Pre-erythrocytic stage, Plasmodium falciparum

microbiology↗

bioRxiv2026

HCN channels enhance synchrony propagation in heterogeneous synfire chains

MotivationInformation flow and temporal coding in cortical circuits depend critically on the reliable transmission of precisely timed synchronous spike patterns. Although cortical assemblies achieve such transmission despite pronounced intrinsic heterogeneities and stochastic high-conductance states, the mechanisms underlying effective synchrony propagation under in vivo conditions remain poorly understood. MethodologyIn this study, we address this gap using large-scale, conductance-based models of excitatory and inhibitory neurons organized into feedforward synfire chains operating in noisy, high-conductance regimes. Using independent stochastic search algorithms, we first identified physiologically valid heterogeneous populations of cortical neurons. Both excitatory and inhibitory populations exhibited cellular-scale degeneracy, whereby distinct combinations of biophysically identified molecular components produced signature physiological characteristics. We then constructed synfire chains with varying degrees of heterogeneity using these populations and assessed the propagation of different spike packets across neuronal assemblies. ResultsWe found synchrony propagation to be inherently probabilistic, revealing a stochastic separatrix that separated input patterns that consistently succeeded from those that consistently failed in propagation. The stochastic nature of this separatrix highlighted a critical role for background synaptic fluctuations, defining a regime in which identical inputs alternately propagated or failed across trials solely due to stochastic background activity. Comparing networks with different degrees of intrinsic heterogeneity, we found that increasing heterogeneity did not alter mean propagation efficacy but reduced network-to-network variability, indicating a stabilizing role for intrinsic diversity. Strikingly, when we tested the impact of neuronal intrinsic properties on synchrony propagation, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels emerged as robust enhancers of synchrony propagation across all heterogeneity regimes. Mechanistically, the slow restorative kinetics of HCN conductances narrowed the temporal window for spike initiation, sharpening output synchrony, and improving propagation reliability. This effect was abolished when HCN kinetics were accelerated, underscoring the importance of the slow negative feedback mediated by these channels. ImplicationsTogether, our analyses identify HCN channels as key regulators of synchronous information transfer and reveal strong interactions among intrinsic conductances, input characteristics, neuronal heterogeneity, and stochastic background activity in shaping cortical synchrony propagation. The ability of diverse cellular and network configurations to achieve similar propagation efficacy further highlights degeneracy as a fundamental principle governing robust and flexible neural computation.

neuroscience↗

bioRxiv2026

Asexual Adaptation Drives Transient and Reversible Changes in Mating Efficiency.

The evolution of reproductive isolation is central to speciation, yet the earliest stages of this process remain poorly understood. In particular, it is unclear how rapidly barriers to mating arise during adaptation, whether they accumulate predictably, and how they depend on ecological context. Here, we investigate the evolution of mating efficiency during prolonged asexual adaptation in diploid Saccharomyces cerevisiae. Twelve replicate populations were evolved for 1200 generations in two distinct carbon environments, glucose and galactose, under strictly asexual conditions. At regular intervals, we induced sporulation and quantified mating efficiency using three complementary assays: within-population crosses, crosses between populations evolved in different environments, and crosses between evolved populations and the ancestral strain. We find that mating efficiency evolves during asexual adaptation, with outcomes that depend strongly on the environment. While glucose-evolved populations remain largely stable, galactose-evolved populations exhibit a reversible decline. Overall, changes in mating efficiency are dynamic, heterogeneous, and often transient, with evidence for both intrinsic reductions in mating competence and context-dependent incompatibilities between populations. Together, these results show that asexual adaptation can generate rapid but non-monotonic changes in mating compatibility. Early reductions in mating efficiency are heterogeneous, environment-dependent, and often reversible, and do not accumulate into stable reproductive isolation over the timescale examined. Our findings suggest that the initial stages of divergence are characterized by dynamic and contingent perturbations of reproductive traits, rather than a steady progression toward speciation.

evolutionary biology↗

bioRxiv2026

Genomic signatures of asymmetric selection on membrane and cytoplasmic proteins.

Protein evolution is influenced by functional, structural, and ecological factors. Here, we propose that subcellular localization adds a critical but less understood dimension to evolutionary constraints. Specifically, we hypothesize that membrane proteins evolve under distinct pressures compared to cytoplasmic proteins, owing to the (a) association between co-translational folding and membrane integration and (b) roles at the interface with dynamic environments. Drawing from comparative genomics data of over 1,000 strains each of Escherichia coli and Saccharomyces cerevisiae, we present evidence suggesting that membrane proteins exhibit increased non-synonymous variation and reduced synonymous variation relative to cytoplasmic proteins. These patterns are stronger in E. coli, as compared to S. cerevisiae. Our data reveal systematic trends consistent with our hypothesis. We argue that recognizing localization-dependent selection could refine our understanding of evolutionary dynamics, inform molecular evolution models, and guide future synthetic and evolutionary studies.

evolutionary biology↗

bioRxiv2026

NR4A1 limits CD8⁺ T Cell effector responses and protection in tuberculosis

During Mycobacterium tuberculosis (Mtb) infection, CD8+ T cells exhibit dysfunction with impaired cytotoxicity and limited localization to granuloma cores. Using knockout mice, adoptive-transfer models and validation in macaque and human datasets, we identified the nuclear receptor NR4A1 as a key restrainer of CD8+ T cell immunity in tuberculosis (TB). Mtb-infected Nr4a1-/- mice displayed reduced bacterial burden, attenuated pathology, higher lung CD8+/CD4+ T cell ratios, and enhanced CD8+ T cell effector functions. Bulk and single-cell RNA sequencing revealed suppression of gene expression program linked with exhaustion, and expansion of Nkg7+ and Granzyme+ cytotoxic CD8+ T cell subsets in Nr4a1-/- mice. Spatial analyses demonstrated increased infiltration of Nkg7+ activated CD8+ T cells in Nr4a1-/- lesions. ChIP-qPCR showed NR4A1 binding to Nkg7 promoter, and Nkg7 knockdown abrogated the enhanced cytotoxicity of Nr4a1-/- CD8+ T cells. Pharmacologic inhibition of NR4A1 reduced Mtb burden and pathology, and restored Nkg7 expression and CD8+ T cell infiltration in the lung. Together, these findings identify NR4A1 as a negative regulator of CD8+ T cell-mediated immunity in TB and suggest the NR4A1-NKG7 axis as a novel host-directed therapeutic target. A one-sentence summary of your paperNR4A1 suppresses CD8+ T cell infiltration and cytotoxicity in TB lesions, and its inhibition enhances host resistance to Mtb infection.

immunology↗

bioRxiv2025

Opposing Copy Number Variation Dynamics Shape Adaptation to Glucose and Galactose in Diploid Yeast

Adaptation to new environments arises from multiple forms of genetic variation, including single-nucleotide polymorphisms (SNPs) and structural variants such as copy number variations (CNVs). Although both mutation classes have been implicated in evolutionary change, their relative contributions during adaptation remain incompletely understood and may depend strongly on environmental context. Here we investigated genome evolution during experimental adaptation of diploid Saccharomyces cerevisiae populations propagated for 1200 generations in two alternative carbon sources, glucose or galactose. Whole-genome sequencing of replicate populations at multiple evolutionary time points revealed relatively few SNPs but widespread copy number variation across the genome. Strikingly, CNV dynamics differed markedly between environments. Populations evolved in glucose exhibited extensive early deletions followed by later genomic remodeling that reduced the overall deletion burden. In contrast, populations evolved in galactose accumulated persistent subtelomeric duplications throughout the experiment. Many loci displayed opposing copy number changes in the two environments, with genes deleted during evolution in glucose frequently duplicated during evolution in galactose. These contrasting trajectories indicate that structural genomic changes repeatedly arise during adaptation and that their direction and persistence depend strongly on environmental conditions. Together, our results illustrate how distinct genomic routes can emerge during adaptation of genetically identical populations and highlight the importance of considering multiple classes of mutations when studying evolutionary responses to environmental change. Impact statementThis study demonstrates that copy number variations (CNVs), rather than single-nucleotide polymorphisms, dominate genome evolution during adaptation of diploid Saccharomyces cerevisiae to alternative carbon sources. By evolving genetically identical populations in glucose and galactose, the work reveals that environmental context drives strikingly opposing CNV trajectories, widespread deletions in glucose and persistent duplications in galactose, often targeting the same genomic loci in opposite directions. These findings provide direct evidence that structurally mediated gene dosage changes are a primary and environment-dependent mechanism of adaptation, reshaping metabolic networks and specialization strategies. More broadly, the study challenges the prevailing SNP-centric view of adaptive evolution and highlights CNVs as a predictable and major axis of genome remodeling in microbial systems.

evolutionary biology↗

bioRxiv2025

Exposure to traffic noise can impact multiple insect fitness components

Noise pollution is a significant environmental stressor that affects organisms physiology and behavior. Due to its wide occurrence and range of component frequencies, traffic noise is a major culprit in this context. Although well-studied in vertebrate systems, the effects of traffic noise on invertebrates remain relatively less explored. This study uses Drosophila melanogaster as a model system to examine the impact of traffic noise on insects. Exposure to traffic noise reduced fecundity in both freshly mated and pre-mated flies, with a more pronounced effect in the former. Additionally, traffic noise increased mating latency but did not affect mating duration. The impact on locomotor activity was sex-specific: while the females remained unaffected, the male flies showed reduced activity regardless of their mating status. Desiccation resistance remained unaffected in both sexes. These findings indicate that traffic noise can decrease fitness in Drosophila melanogaster, which aligns with some (but not all) previous observations on other insect species. The long-term ecological implications of such noise include potential disruptions in insect-mediated ecosystem services, which can threaten the overall ecological balance. Summary StatementTraffic noise impairs fruit-flys fecundity, extends mating latency, and reduces male locomotor activity, suggesting that such noise can potentially reduce fitness and risk insect-driven ecosystem services.

ecology↗

bioRxiv2025

Facultative Cheating and Hybrid Vigor Resolves Cooperator-Cheater Conflict in a Yeast Public Goods System.

The persistence of cooperation in the face of cheating is a central paradox in evolutionary biology. Microbial public goods systems employ diverse solutions to this dilemma, yet most studies assume fixed strategies wherein genotypes function strictly as cooperators or cheaters. Here, using the GAL/MEL regulon of Saccharomyces cerevisiae, we uncover a dynamic resolution to this conflict through facultative strategy switching. When haploid cheater-cooperator strains were co-evolved in melibiose, we observed the repeated emergence of same-mating-type diploid hybrids. These hybrids arise early in evolution and ultimately spread in the population. The hybrids exploit the public good produced by cooperator strains when present, acting as facultative cheaters. However, following cooperator extinction, hybrids switch to a cooperative phenotype. This dynamic role transition enables the hybrid to persist across shifting ecological contexts. Our findings reveal a novel, context-dependent mechanism of cooperation maintenance, whereby facultative cheating and genotype plasticity resolve the tension between individual fitness and collective benefit. This work expands the conceptual framework of social evolution by demonstrating that phenotypic flexibility, facilitated through hybridization, can stabilize cooperation even in fully exploitable public goods systems.

evolutionary biology↗

bioRxiv2025

Perinatal Nicotine Exposure Disrupts Hematopoietic Stem Cell Development and Elevates Influenza Susceptibility in Adulthood

Tobacco use during pregnancy has many deleterious health consequences for not only the smoking mother, but also on the unborn fetus. Children of smoking mothers are reported to have higher frequency and severity of respiratory diseases later in life; however, the mechanisms driving this increased vulnerability are not clearly understood. One potential cause of increased disease susceptibility is an altered immune system, originating in epigenetically maladaptive hematopoietic stem cells (HSCs). Here, we show that perinatal nicotine exposure (PNE) alters the establishment of HSCs and fetal-derived non-traditional tissue immune cells, with no alterations in circulating immune cell numbers. Suppression of HSCs and lung immune cells persisted for weeks after PNE had ceased. Strikingly, PNE led to increased disease susceptibility and severity upon challenge with influenza A virus in adulthood. This was associated with significant and highly selective alterations in lung immune cells, emphasizing the importance of cellular mechanisms in resilience to infections. Together, these experiments demonstrate that perinatal exposures that have deleterious consequences on hematopoietic establishment can impair immune function for life and identify the cellular mechanisms by which perinatal nicotine exposure predisposes the offspring to a weakened defense against respiratory pathogens. HIGHLIGHTSO_LIPerinatal nicotine exposure (PNE) causes long-term alterations of hematopoiesis C_LIO_LIPNE perturbs hematopoietic stem cell (HSC) development and maintenance C_LIO_LIPNE diminishes the population of fetal-derived tissue-resident alveolar macrophages C_LIO_LIPNE alters cellular mechanisms, exacerbating disease severity later in life C_LIO_LINicotine suppression of central immunity is manifested mechanistically by altered immune cell output C_LI

developmental biology↗

bioRxiv2025

Degeneracy explains diversity in interneuronal regulation of pattern separation in heterogeneous dentate gyrus networks

Background and motivationsThe Marr-Albus theory postulates that pattern separation is realized by divergent feedforward excitatory connectivity. Yet, there are several lines of evidence for strong but differential regulation of pattern separation by local circuit connectivity, even when feedforward connectivity is divergent. What are the relative contributions of divergent feedforward connectivity and local circuit interactions to pattern separation? How do we reconcile the contrasting lines of evidence on local circuit regulation of pattern separation in circuits endowed with divergent feedforward connectivity? In this study, we quantitatively address these questions in a population of heterogeneous dentate gyrus (DG) networks, where we enforced feedforward connectivity to be identically divergent. MethodologyWe generated tens of thousands of random spiking neuronal models to arrive at thousands of non-repeating heterogeneous single-neuron models of four different DG neuronal subtypes, each satisfying their respective functional characteristics. We connected these heterogeneous populations of neurons with subtype proportions and local connectivity that reflected the DG microcircuit. In a second level of unbiased search, we generated 20,000 identical networks that differed from each other only in their synaptic weight values. Thus, within the Marr-Albus framework, these networks that were identical in terms of neuronal composition and divergent feedforward connectivity should all be capable of performing effective pattern separation. To test this, we fed these networks with morphed sets of input patterns, recorded granule cell outputs, and computed similarity metrics based on correlation measures across input or output patterns. We developed novel quantitative metrics for pattern separation from plots of output similarity vs. input similarity and validated each network with bounds on these metrics. ResultsDespite being identical in terms of divergent feedforward connectivity, we found only a very small proportion (47 of 20,000 or 0.23%) of the randomly generated networks to manifest effective pattern separation. We tested the specific contributions of interneurons by assessing pattern separation in all pattern-separating networks after individually deleting each of the three interneuron subtypes. Strikingly, we found pronounced network-to-network variability in how each interneuron subtype contributed to granule cell sparsity and pattern separation. We traced this variability to differences in local synaptic connectivity, which also resulted in network-to-network variability in firing rates and sparsity of different interneurons. Finally, we found heterogeneous DG networks to be more resilient to synaptic jitter compared to their homogeneous counterparts, with specific reference to pattern separation computed through average firing rate correlations. ImplicationsOur population-of-networks approach clearly shows that divergent connectivity of afferent inputs does not guarantee pattern separation in DG networks. Instead, we demonstrate strong yet variable roles for interneurons and local connectivity in implementing pattern separation. Importantly, our analyses unveil degeneracy in DG circuits, whereby similar pattern separation efficacy was achieved through disparate local-circuit interactions. These observations, alongside network-to-network variability in dependencies on different interneurons, strongly advocate the complex adaptive systems approach as a unifying framework to study DG pattern separation.

neuroscience↗

bioRxiv2025

On the metabolic basis and predictability of global epistasis.

Epistasis, where a mutations effect depends on genetic background, is central to evolution. A striking pattern, global epistasis, results in fitness effects varying systematically with background fitness--often making beneficial mutations less effective in fitter genotypes. Despite its ubiquity and importance in predicting evolution, the cellular origin of this pattern is unclear. We present a microbial cell growth model and show that global epistasis arises naturally from the underlying metabolic structure, and is modulated by reaction speeds and flux redistribution in the cell. Mutations in standalone rate-limiting modules yield predictable fitness effects, while those in interconnected modules behave idiosyncratically. As genetic divergence increases, background fitness becomes a poorer predictor of fitness effects. Our framework links cellular metabolism to adaptation, offering mechanistic insights into evolutionary predictability.

evolutionary biology↗

bioRxiv2024

Experimental evolution of Drosophila without its microbiome

In single-generation experiments, microbiome removal often affects multiple host traits. However, relatively little is understood about the long-term implications of living in a microbe-free environment. To address this question, we evolved four replicate laboratory populations of Drosophila melanogaster without microbes and compared their traits with corresponding control populations that were reared with microbiota. This comparison was done under two assay environments: with-microbes and microbe-free. Prior single-generation experiments on our populations had revealed that microbiota removal significantly affects multiple traits, which suggested that the flies were under strong selection pressure to adapt to the absence of microbes. However, contrary to our expectations, the selected populations underwent very modest changes even after 54-57 generations of selection. Moreover, the magnitude of change in trait values across the with- and without- microbe environments was less for the selected populations than for the controls. RNA-Seq on one of the evolutionary replicates revealed that compared to the control, some anti-microbial peptides (AMPs) in the selected population were up-regulated, while several heat shock proteins (HSPs) were down-regulated. These results suggest that robust host-microbiome integrations on short timescales can nevertheless be labile on longer timescales. We situate these results in the context of the "evolutionary addiction hypothesis" and the "hygiene hypothesis".

evolutionary biology↗

bioRxiv2024

Resource presentation dictates genetic and phenotypic adaptation in yeast.

Environments shape adaptive trajectories of populations, often leading to adaptive parallelism in identical, and divergence in different environments. However, how does the likelihood of these possibilities change with minute changes in the environment? In this study, we evolve Saccharomyces cerevisiae in environments which only differed in how sugar source is presented to the population. In one set of populations, carbon was presented as a mixture of glucose-galactose, and in the other, as melibiose, a glucose-galactose disaccharide. Since the two environments only differ in how the two monosaccharides are packaged, we call these environments "synonymous". Our results show that subtle changes in environments change the targets of selection between the two sets of evolved populations. However, despite different adaptive responses, pleiotropic effects of adaptation are largely predictable. Genome sequencing results demonstrate that small changes in the environment also strongly dictates the genetic basis of adaptation.

evolutionary biology↗

bioRxiv2024

Synonymous and single nucleotide changes facilitate the adaptation of a horizontally transferred gene.

The movement of genes between microbial species, or horizontal gene transfer, is common. While this process speeds up adaptation, the functionality of horizontally transferred genes is highly constrained in the new hosts due to several reasons, and protein localization is one of them. In this study, we ask what is the minimum number of mutations that can resolve a localization problem faced by a horizontally transferred protein in a new host. Using a directed-evolution approach, we show that SNPs and a synonymous mutation can change the localization patterns of an ammonia transporter (AmtA) moved from Dictyostelium discoideum to Saccharomyces cerevisiae. Interestingly, the mutations that cause this change in localization, confer different fitness effects, are spread throughout the gene, and do not cause a uniform change in amino acids. In a novel attempt, we show how SNPs or a synonymous mutation can alter the membrane affinity of proteins, and as a result, aiding protein evolution and functional diversification.

evolutionary biology↗

bioRxiv2024

Variations and predictability of epistasis on an intragenic fitness landscape.

How epistasis hinders or facilitates movement on fitness landscapes has been a longstanding question in evolutionary biology. High-throughput experiments have revealed that, despite their idiosyncratic nature, epistatic interactions can exhibit reproducible global statistical patterns. Recently, Papkou et al. constructed a fitness landscape for a 9-base pair region of the folA gene in Escherichia coli, which encodes dihydrofolate reductase (DHFR), and showed that this landscape is both rugged and highly navigable. Here, we analyze this landscape to address two questions: How does the nature of epistasis between two mutations change with genetic background? and How predictable is epistasis within a gene? We find that epistasis is "fluid": higher-order interactions cause the relationship between two mutations to shift strongly across genetic backgrounds. Mutations fall into two distinct categories: a small subset exhibit strong global epistasis, while the majority do not. Nonetheless, we find that the distribution of fitness effects (DFE) of a genotype is highly predictable from its fitness. These findings provide a gene-level perspective on how epistasis operates, revealing both its unpredictability and its statistical regularities, and offer a framework for predicting mutational effects from high-dimensional fitness landscapes. Significance Statement.The effect of a mutation on fitness depends on the genome in which it occurs, a phenomenon known as epistasis. Epistasis makes evolution difficult to predict, but recent work has uncovered statistical regularities in how it manifests. Using a fitness landscape of [~]260,000 variants of an E. coli gene, we show that higher-order interactions make pair-wise epistasis "fluid": the relationship between two mutations changes with genetic background. We also find that epistasis is "binary" - a small subset of mutations exhibits strong global statistical patterns, while most do not. These findings reveal new principles of how epistasis shapes protein evolution and, ultimately, organismal adaptation.

evolutionary biology↗

bioRxiv2024

Adaptive and pleiotropic effects of evolution in synonymous sugar environments.

Adaptation to an environment is enabled by the accumulation of beneficial mutations. When adapted populations are shifted to other environments, the byproduct or pleiotropic fitness effects of these mutations can be wide-ranged. Since there exists no molecular framework to quantify relatedness of environments, predicting pleiotropic effects based on adaptation has been challenging. In this work, we ask if evolution in highly similar environments elicits correlated adaptive and pleiotropic responses. We evolve replicate populations of Escherichia coli in non-stressful environments that contain either a mixture of glucose and galactose, lactose, or melibiose as the source of carbon. We term these similar sugars as "synonymous", since lactose and melibiose are disaccharides made up of glucose and galactose. Therefore, the evolution environments differed only in the way carbon was presented to the bacterial population. After 300 generations of evolution, we see that the adaptive responses of these populations are not predictable. We investigate the pleiotropic effects of adaptation in a range of non-synonymous environments, and show that despite uncorrelated adaptive changes, the nature of pleiotropic effects is largely predictable based on the fitness of the ancestor in the non-home environments. Overall, our results highlight how subtle changes in the environment can alter adaptation, but despite sequence-level variations, pleiotropy is qualitatively predictable. Lay SummaryIn nature, evolution in "similar" environments is believed to elicit identical responses. For example, the arctic fox and ptarmigan, which are two unrelated species living in the arctic, have evolved to turn white in the winters. They did not evolve this ability because they from the common ancestor, but because the environment favoured this trait. In this work, we ask what happens to evolving populations if there are minute changes in the environment, and what are the consequences of adapting in these environments that are "almost identical", or as we call them, "synonymous". We evolve replicate populations of the bacteria E. coli in three synonymous environments, and quantify their ability to grow in both synonymous and non-synonymous environments. We see that evolution does not proceed in an identical fashion in these populations, and that each environment favours a different trait. However, interestingly, in non-synonymous environments, these three sets of populations perform almost identically, and their growth is qualitatively predictable. Our results show that even simple and subtle changes in the environment can act as drivers of biodiversity.

evolutionary biology↗

bioRxiv2024

Empirical evidence of resource dependent evolution of payoff matrices in Saccharomyces cerevisiae populations.

In evolutionary game theory, a relative comparison of the cost and benefit associated with obtaining a resource, called payoff, is used as an indicator of fitness of an organism. Such payoff matrices are used to understand complex inter-species and intra-species interactions like cooperation, mutualism, and altruism. In the absence of any empirical data, the evolution of these payoff matrices has been investigated theoretically by tweaking well-established game theory models. In this paper, we present empirical evidence of three types of resource-dependent changes in the payoff matrices of evolving Saccharomyces cerevisiae populations. We show that depending on the carbon source and participating genotypes, the payoff matrix could either (a) evolve quantitatively yet maintain a cheater-cooperator game, (b) change qualitatively such that the cheater-cooperator game collapses, or (c) change qualitatively to result in the birth of a cheater-cooperator game. Our results highlight the need to consider the dynamic nature of payoff matrices while making even short-term predictions about population interactions and dynamics.

evolutionary biology↗

bioRxiv2023

Maintenance of cooperation in a yeast population in a public-good driven system.

The phenomenon of cooperation is prevalent at all levels of life. In microbial communities, some groups of cells exhibit cooperative behaviour by producing costly extracellular resources that are freely available to others. These resources are referred to as public goods. Saccharomyces cerevisiae secretes invertase (public good) in the periplasm to hydrolyse sucrose into glucose and fructose, which are further imported by the cells. After hydrolysis of sucrose, the cells retain only 1% of the monosaccharides, while 99% diffuse into the environment and can be utilised by all neighbouring cells. The non-producers of invertase (cheaters) exploit the invertase-producing cells (cooperators) by utilising the monosaccharides and paying nothing for the latter. In this work, we investigate the evolutionary dynamics of this cheater-cooperator system. If cheaters are selected for their higher fitness, the population will collapse. For cooperators to survive cheating and thrive in nature, they should have evolved some survival strategies. To understand the adaptation of cooperators in sucrose, we performed a coevolution experiment in sucrose. Our results show that cooperators increase in fitness as the experiment progresses. This phenomenon was not observed in environments which involved a non-public good system. Genome sequencing reveals the molecular basis for the cooperator adaptating is because of increased privatization of the public-good released carbon resource.

evolutionary biology↗