Biology subjects

Garud, N.

Publications and source records attributed to Garud, N..

6 recordsLinked to original sources

bioRxiv2026

Growth capacity and mortality burden shape microbial persistence under osmotic stress in Bacteroides thetaiotaomicron

Microbial persistence in the gut is central to sustaining beneficial host-microbiota interactions; however, characterizing determinants of persistence in vivo can be challenging due to the complexity of native microbial communities interacting with the host. Here, we used a defined microbial consortium to demonstrate that intrinsic in vitro growth capacity becomes increasingly predictive of in vivo relative abundance as intestinal osmolality increases. In Bacteroides thetaiotaomicron, in vivo abundance was higher than predicted from growth capacity alone, indicating that additional physiological factors contribute to persistence. We identify mortality as one such determinant: adaptation to prolonged osmotic stress markedly reduced cell loss without enhancing growth capacity. This adaptive phenotype was associated with rapid and reversible phase variation in cell surface-associated PUL78/80 rather than fixed de novo mutations, with the PUL78/80-OFF state becoming progressively enriched among surviving cells as mortality increased. Our findings demonstrate that in addition to growth capacity, reduced cell loss can provide a distinct route to microbial persistence during environmental perturbation.

microbiology↗

bioRxiv2025

The persistence and loss of hard selective sweeps amid ancient human admixture

The extent to which human adaptations have persisted throughout history despite strong eroding demographic events such as admixture, genetic drift, and fluctuations in selection pressures remains unknown. Understanding which adaptations were resilient to such forces may shed light on traits that were important for humans across time. Yet, detecting selection from ancient DNA is challenging due to severe degradation of the data and/or signal. Here we detect selective sweeps using a domain-adaptive neural network (DANN) trained on simulated data and applied to more than 800 ancient and modern Eurasian genomes spanning the last 7000 years. We show that the DANN can account for simulation misspecification, or discrepancies between simulations and real aDNA, improving the ability to detect sweeps in real data compared to standard convolutional neural networks or standard statistics. Application of the DANN to data recovered 16 known sweeps at loci including LCT, HLA, KITLG, and OCA2/HERC2, and revealed 32 novel sweeps. All identified sweeps were classified as hard, consistent with historically low population sizes. While some sweeps were lost over time, 14 sweeps at loci involved in functions including neuronal, reproductive, pigmentation, and signaling traits persisted from the earliest to the most recent time periods. In most cases, the most frequent haplotype remained at high frequency across time. Together, these results indicate that hard sweeps predominated in ancient Eurasians and that several ancient selective events were resilient to strong admixture events. Significance statementThe extent to which human adaptations have persisted despite strong eroding forces such as admixture, drift, or fluctuations in selection pressures remains unknown. Understanding which loci are particularly resilient to such forces may shed light on the traits that were important for humans across time. Using a domain-adaptive neural network that accounts for simulations with misspecified demography relative to the data, we discover several sweeps at loci encoding neuronal, reproductive, pigmentation, and signaling traits persisted from the earliest time periods to the present, revealing the resilience of these sweeps to strong admixture events. Moreover, we find that hard sweeps, driven by single beneficial mutations, dominated throughout human history, consistent with the historically low human population sizes.

evolutionary biology↗

bioRxiv2024

A conserved genetic basis for commensal-host specificity through live imaging of colonization dynamics

Animals throughout the metazoa selectively acquire specific symbiotic gut bacteria from their environment that aid host fitness. Current models of colonization suggest these bacteria use weakly specific receptors to stick to host tissues and that colonization results when they stick in a region of the host gut that overlaps with their nutritional niche. An alternative model is that unique receptor-ligand binding interactions provide specificity for target niches. Here we use live imaging of individual symbiotic bacterial cells colonizing the gut of living Drosophila melanogaster to show that Lactiplantibacillus plantarum specifically recognizes a distinct physical niche in the host gut. We find that recognition is controlled by a colonization island that is widely conserved in commensals and pathogens from the Lactobacillales to the Clostridia. Our findings indicate a genetic mechanism of host specificity that is broadly conserved. One-Sentence SummaryHost-symbiont specificity is encoded by a conserved colonization island that provides molecular precision to host niche access.

microbiology↗

bioRxiv2023

Pervasive selective sweeps across human gut microbiomes

The human gut microbiome is composed of a highly diverse consortia of species which are continually evolving within and across hosts. The ability to identify adaptations common to many human gut microbiomes would not only reveal shared selection pressures across hosts, but also key drivers of functional differentiation of the microbiome that may affect community structure and host traits. However, to date there has not been a systematic scan for adaptations that have spread across human gut microbiomes. Here, we develop a novel selection scan statistic named the integrated Linkage Disequilibrium Score (iLDS) that can detect the spread of adaptive haplotypes across host microbiomes via migration and horizontal gene transfer. Specifically, iLDS leverages signals of hitchhiking of deleterious variants with the beneficial variant. Application of the statistic to[~] 30 of the most prevalent commensal gut species from 24 populations around the world revealed more than 300 selective sweeps across species. We find an enrichment for selective sweeps at loci involved in carbohydrate metabolism--potentially indicative of adaptation to features of host diet--and we find that the targets of selection significantly differ between Westernized and non-Westernized populations. Underscoring the potential role of diet in driving selection, we find a selective sweep absent from non-Westernized populations but ubiquitous in Westernized populations at a locus known to be involved in the metabolism of maltodextrin, a synthetic starch that has recently become a widespread component of Western diets. In summary, we demonstrate that selective sweeps across host microbiomes are a common feature of the evolution of the human gut microbiome, and that targets of selection may be strongly impacted by host diet.

evolutionary biology↗

bioRxiv2023

Inference of the demographic histories and selective effects of human gut commensal microbiota over the course of human history

Despite the importance of gut commensal microbiota to human health, there is little knowledge about their evolutionary histories, including their population demographic histories and their distributions of fitness effects (DFE) of new mutations. Here, we infer the demographic histories and DFEs of 27 of the most highly prevalent and abundant commensal gut microbial species in North Americans over timescales exceeding human generations using a collection of lineages inferred from a panel of healthy hosts. We find overall reductions in genetic variation among commensal gut microbes sampled from a Western population relative to an African rural population. Additionally, some species in North American microbiomes display contractions in population size and others expansions, potentially occurring at several key historical moments in human history. DFEs across species vary from highly to mildly deleterious, with accessory genes experiencing more drift compared to core genes. Within genera, DFEs tend to be more congruent, reflective of underlying phylogenetic relationships. Taken together, these findings suggest that human commensal gut microbes have distinct evolutionary histories, possibly reflecting the unique roles of individual members of the microbiome.

evolutionary biology↗

bioRxiv2020

Genetic Adaptation in New York City Rats

Brown rats (Rattus norvegicus) thrive in urban environments by navigating the anthropocentric environment and taking advantage of human resources and by-products. From the human perspective, rats are a chronic problem that causes billions of dollars in damage to agriculture, health and infrastructure. Did genetic adaptation play a role in the spread of rats in cities? To approach this question, we collected whole-genome sequences from 29 brown rats from New York City (NYC) and scanned for genetic signatures of adaptation. We tested for (i) high-frequency, extended haplotypes that could indicate selective sweeps and (ii) loci of extreme genetic differentiation between the NYC sample and a sample from the presumed ancestral range of brown rats in northeast China. We found candidate selective sweeps near or inside genes associated with metabolism, diet, the nervous system and locomotory behavior. Patterns of differentiation between NYC and Chinese rats at putative sweep loci suggests that many sweeps began after the split from the ancestral population. Together, our results suggest several hypotheses on adaptation in rats living in close proximity to humans.

evolutionary biology↗