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PubMed1995

Inferring weak selection from patterns of polymorphism and divergence at "silent" sites in Drosophila DNA.

Patterns of codon usage and "silent" DNA divergence suggest that natural selection discriminates among synonymous codons in Drosophila. "Preferred" codons are consistently found in higher frequencies within their synonymous families in Drosophila melanogaster genes. This suggests a simple model of silent DNA evolution where natural selection favors mutations from unpreferred to preferred codons (preferred changes). Changes in the opposite direction, from preferred to unpreferred synonymous codons (unpreferred changes), are selected against. Here, selection on synonymous DNA mutations is investigated by comparing the evolutionary dynamics of these two categories of silent DNA changes. Sequences from outgroups are used to determine the direction of synonymous DNA changes within and between D. melanogaster and Drosophila simulans for five genes. Population genetics theory shows that differences in the fitness effect of mutations can be inferred from the comparison of ratios of polymorphism to divergence. Unpreferred changes show a significantly higher ratio of polymorphism to divergence than preferred changes in the D. simulans lineage, confirming the action of selection at silent sites. An excess of unpreferred fixations in 28 genes suggests a relaxation of selection on synonymous mutations in D. melanogaster. Estimates of selection coefficients for synonymous mutations (3.6 < magnitude of Nes < 1.3) in D. simulans are consistent with the reduced efficacy of natural selection (magnitude of Nes < 1) in the three- to sixfold smaller effective population size of D. melanogaster. Synonymous DNA changes appear to be a prevalent class of weakly selected mutations in Drosophila.

Animals↗

PubMed2025

Chromosome-Level Genome Assembly of Eden's Whale Clarifies the Taxonomy and Speciation of Bryde's Whale Complex.

Eden's whale (Balaenoptera edeni), a poorly understood baleen cetacean, has long been shrouded in taxonomic ambiguity due to limited genomic resources, obscuring its distinction from closely related species and its position within the cetacean Tree of Life. In this paper, we present a high-quality chromosomal-level genome of B. edeni and conduct comparative genomic analyses to address long-standing taxonomic confusion and elucidate speciation of balaenopterids. Our phylogenomic analysis and demographic reconstruction reveal that B. edeni is a distinct sister to Bryde's whale (Balaenoptera brydei), sharing a common ancestor that diverged approximately 7.84 million years ago during the late Miocene. Their genetic divergence exceeds typical intraspecific variation in whales, supporting the reinstatement of B. brydei as a valid species. Chromosomal syntenic analyses suggest that macro-fragment inversions contributed to speciation in balaenopterid whales and uncover unexpected large-scale complex genome rearrangements in Bryde's whale, offering novel insights into cetacean genome evolution. Functional enrichment analysis of inverted regions between B. edeni and Balaenoptera musculus indicates their predominant association with metabolism and biosynthesis, as well as responses to various substances, stress, and stimuli. These genomic resources for B. edeni not only lay a critical foundation for comparative genetic and evolutionary research of cetaceans but also advance our understanding of the taxonomy and evolutionary dynamics of the Bryde's whale complex, with broader implications for baleen whale conservation and biodiversity.

Animals↗

PubMedDate not supplied

The mtDNA genealogy of closely related Drosophila silvestris.

Genetic, morphological, and behavioral analyses have been used to examine the evolutionary dynamics and phylogeny of the rare Hawaiian Drosophila species, D. silvestris. Critical to understanding the evolution of this species is the examination of the distribution of populations of D. silvestris on the Big Island of Hawaii. Behavioral analysis using mating asymmetries and the Kaneshiro hypothesis as an indicator of ancestral behavioral state has suggested that flies from the northern part of the island are ancestral to those on the southern part of the island. Consequently, a sequential pattern of colonization going from north to south is predicted for these flies on the east side of the Island of Hawaii. We have examined this prediction using mitochondrial DNA (mtDNA) restriction site analysis with four-base cutters and DNA sequencing. The resulting mtDNA phylogeny based on 23 phylogenetically informative restriction sites and two phylogenetically informative DNA sequence characters agrees in part with the phylogeny predicted from the behavioral data.

Animals↗

PubMed2026

Whole-genome characterization and phylogenetic placement of Fusarium oxysporum f. sp. vasinfectum isolates.

Fusarium wilt of cotton, caused by Fusarium oxysporum f. sp. vasinfectum (Fov), remains a persistent threat to cotton production worldwide. Among the known races, Fov race 4 and its extra-virulent variants cause particularly severe losses in Upland cotton. Although several Fov genome assemblies have been assigned to races, the genomic diversity and evolutionary relationships among pathogenic and non-pathogenic isolates associated with cotton outbreaks remain poorly understood at the whole-genome level. This study addressed these gaps by generating and comparing high-quality genome assemblies of four Fusarium isolates collected from Texas cotton fields: two pathogenic (TX17-24 and TX18-9) and two non-pathogenic (TX17-6 and TX18-6). Draft assemblies were generated using Oxford Nanopore long reads and polished with Illumina reads. Comparative genomic analyses showed that pathogenic isolates possessed larger genomes and more conserved orthologous families, whereas non-pathogenic isolates contained more unique genes. Analyses of predicted secreted effectors, transposable elements, and carbohydrate-active enzymes further distinguished pathogenic and non-pathogenic lineages, suggesting roles in virulence adaptation and genome plasticity. Phylogenomic analyses using k-mer-based, assembly- and alignment-free methods incorporated all available long-read Fov genomes and revealed substantial genetic diversity within races 1 and 4, clustering isolates into multiple sublineages. These findings show that Fov race diversification is underestimated when based on traditional classification schemes and may be shaped by host specialization, geographic separation, or horizontal gene transfer. This work advances our understanding of the genomic diversity and evolutionary dynamics of Fov and establishes a foundation for improved race identification and characterization of Fusarium wilt pathogenesis in cotton.

Fusarium oxysporum↗

PubMed2026

Trade-Offs Associated with Virulence of Soybean Cyst Nematode on the Broad-Spectrum Resistance Source PI 437654.

The soybean cyst nematode (SCN; Heterodera glycines) poses a major challenge to soybean production, intensified by the declining effectiveness of natural resistance against this pathogen. Although the use of resistant soybean varieties can be effective, their widespread and repeated use ultimately results in the emergence of virulent nematode populations that can successfully attack these resistant hosts. To assess for potential trade-offs between virulence and fitness, we investigated the hatch response, penetration rate, and reproductive potential of SCN adapted to overcome the broad-spectrum resistance source PI 437654. The hatching process is a critical phase in the life cycle of the SCN, influencing its ability to infect hosts and complete its life cycle. Our results indicated that SCN populations exhibit preferential and heightened hatch responses to their adapted host compared to alternative hosts, regardless of their virulence profile. Additionally, we found that SCN populations adapted to overcome broad-spectrum resistance showed reduced reproductive success on susceptible hosts compared to unadapted populations. This reduction in reproductive success was not attributed to differences in hatch response or penetration rates. The results from our study highlight the potential trade-offs associated with SCN virulence adaptation and emphasize the importance of considering these evolutionary dynamics in developing sustainable management strategies.

Disease Control and Pest Management↗

PubMed1995

Coinfection and the evolution of parasite virulence.

Analyses of the selection pressures acting on parasite virulence are made more complicated when individual hosts can simultaneously harbour many different strains or genotypes of a parasite. Here we explore the evolutionary dynamics of host-parasite associations in which individual hosts can be coinfected with many different parasite strains. (We take coinfection to mean that each strain transmits at a rate unaffected by the presence of others in the same host.) This study thus represents the opposite extreme to our earlier work on superinfection in which there is a dominance hierarchy such that only the most virulent strain present in a host is transmitted. For highly diverse populations of parasite strains, we find that such coinfection leads to selection for strains whose virulence-levels lie in a relatively narrow band close to the maximum consistent with the parasite's basic preproductive ratio, R0, exceeding unity.

Animals↗

PubMed2025

Intracellular interactions shape antiviral resistance outcomes in poliovirus via eco-evolutionary feedback.

Antiviral resistance evolution poses a major obstacle for controlling viral infections. A promising strategy is to target shared viral proteins that allow drug susceptible viruses to sensitize resistant ones during cellular coinfection, muting selection for resistance. Pocapavir, a poliovirus capsid inhibitor, employs this sociovirological strategy. While susceptible viruses significantly suppressed resistance in the presence of pocapavir in cell culture, a pocapavir clinical trial observed widespread resistance evolution and limited improvements to clearance times. To reconcile these findings, we present an intra-host eco-evolutionary model of poliovirus in the presence of pocapavir, which reproduces both the potent interference observed in vitro and the resistance emergence seen in patients. In the short term, our model predicts that a high density of susceptible viruses sensitizes resistant ones to pocapavir, mirroring cell culture results. However, over multiple replication cycles, pocapavir's high potency collapses viral density, which reduces coinfection and allows resistance to evolve as observed in the clinical trial. Since coinfection is essential to suppress resistance, enabling greater survival of susceptible viruses could offer therapeutic advantages. Counterintuitively, we demonstrate that this can be achieved by lessening antiviral potency, which can limit resistance evolution while also maintaining a low viral load. These findings suggest that antivirals that rely on viral intracellular interaction must balance immediate neutralization with the preservation of future coinfection, yielding more sustained inhibition. Explicitly considering the eco-evolutionary feedback encompassing viral density, shared phenotypes and absolute fitness not only provides new insights into designing effective therapies but also illuminates viral evolutionary dynamics more broadly.

Journal Article↗

PubMed2026

Nuclear mitochondrial sequences in great ape telomere-to-telomere genomes.

Mitochondrial sequences have integrated into the nuclear genome since the origin of eukaryotes. Recent insertions that retain homology with extant mitochondrial DNA (mtDNA), termed NUMTs, confound mtDNA sequence analysis. Here, we use great ape telomere-to-telomere (T2T) genomes to study NUMTs in bonobo, chimpanzee, human, gorilla, and Bornean and Sumatran orangutans. A phylogeny based on shared and lineage-specific NUMTs accurately recapitulates the great ape species tree topology. NUMTs are enriched at nonfunctional nonrepetitive regions of the nuclear genome and depleted within enhancers and coding sequences, suggesting negative selection. We validate the presence of a 76-kb-long heterozygous NUMT in chimpanzee, which is larger than any other NUMT observed in great apes, and find that dozens of NUMTs on the Pan Y Chromosome expanded together with palindromes. Finally, by analyzing intra-specific variation, we confirm that the vast majority of species-specific NUMTs identified in T2T assemblies are fixed or present at high frequencies in each species. Our study highlights NUMTs as a dynamic evolutionary force contributing to shaping ape genomes and is valuable for characterizing mtDNA in great apes.

Journal Article↗

PubMed2025

Contrasting Genomic Responses of Hydrothermal Vent Animals and Their Symbionts to Population Decline After the Hunga Volcanic Eruption.

Genetic bottlenecks are evolutionary events that reduce the effective size and diversity of natural populations, often limiting a population's ability to adapt to environmental change. Given the accelerating human impact on ecosystems worldwide, understanding how populations evolve after a genetic bottleneck is becoming increasingly important for species conservation. Ash deposits from the 2022 Hunga volcanic eruption in the Southwest Pacific led to a drastic decline of animal symbioses associated with hydrothermal vents in this region, allowing insights into the effects of population bottlenecks in the deep sea. Here, we applied metagenomic sequencing to pre- and post-eruption samples of mollusc-microbial symbioses from the Lau Basin to investigate patterns of genetic variation and effective population size. Our data indicate that animal host populations currently show only small changes in genome-wide diversity but in most cases experienced a long-term decline in effective size that was likely intensified by the volcanic impact. By contrast, host-associated symbiont populations exhibited a notable decrease in genomic variation, including potential loss of certain habitat-specific strains. However, detection of environmental sequences resembling mollusc symbionts suggests that lost host-associated symbiont diversity might be recovered from the free-living symbiont pool. The differences between host and symbiont populations might be related to their contrasting genetic structures and pre-existing levels of connectivity, although the full extent of population bottlenecks in the host animals might only be recognisable after a few generations. These results add to our understanding of the evolutionary dynamics of animal-microbe populations following a natural disturbance and help assess their resilience to both natural and anthropogenic impacts.

Animals↗

PubMed2026

Unraveling epigenetic and genetic variations in response to cold stress in two lotus ecotypes.

Genetic variations accumulate over long evolutionary timescales, whereas epigenetic modifications can arise rapidly and be inherited across generations. However, the interplay between genetic and epigenetic variations in shaping ecotype-specific phenotypic plasticity remains elusive. Focusing on two lotus ecotypes that evolved under distinct winter temperature regions and display divergent annual growth cycles under cold stress, we generated DNA methylation landscapes across three sequence contexts (CG, CHG, and CHH, where H = A, T, or C) and identified single-cytosine methylation polymorphisms (SMPs) and single-nucleotide polymorphisms (SNPs). Interestingly, only CG methylation patterns mirror population-level genetic variations. Using epigenetic genome-wide association analysis, we identified differentially methylated CG sites that are either cis- or trans-regulated by SNP. Notably, we constructed a multifactorial regulatory network centered on the NnMKK4-NnCYCD5 module, linking cold response with cell cycle regulation. Temperature stress experiments conducted on lotus ecotypes and transgenic Arabidopsis (OE-NnMKK4 and OE-NnCYCD5) confirmed that NnMKK4 acts as a cold receptor and that NnCYCD5 promotes cell cycle progression and growth under cold conditions. Collectively, our findings provide novel insights into the co-evolutionary dynamics of epigenetic and genetic variations that are associated with different growth cycles of lotus ecotypes in response to cold stress.

DNA methylation↗

PubMed2025

The evolutionary trajectories and gene regulatory roles of nuclear-integrated plastid DNA: clues for enhancing environmental adaptation in Caryophyllales.

Environmental stimuli can induce the transfer of chloroplast DNA to the nuclear genome, resulting in nuclear-integrated plastid DNAs (NUPTs). However, their role in plant adaptability remains unclear. Species within the Caryophyllales order, known for their adaptation to extreme environments, provide an ideal model for studying the evolutionary dynamics and functions of NUPTs. In this study, we analyzed NUPTs in 24 Caryophyllales species to investigate their evolution and regulatory roles in gene expression, particularly in response to environmental stimuli. We found significant interspecies variation in NUPT abundance, ranging from 566 insertions in Amaranthus cruentus to 3585 in Beta vulgaris, with sizes spanning from 100 bp to over 100 kb. Approximately 62% of NUPTs were inserted within the last 20 million years, while some species exhibit insertion peaks dating back 49 million years. NUPT presence/absence polymorphisms in six related species suggest that NUPT insertions and deletions are dynamic processes influenced by phylogeny. NUPTs predominantly integrate into intergenic regions but also insert into genes and promoters, with certain regions acting as hotspots. Notably, NUPTs introduce numerous environmental-responsive cis-acting elements in promoter regions. Genes with NUPT insertions in their promoters are significantly enriched for functions related to environmental response. Further luciferase assays in Spinacia oleracea demonstrated that NUPT insertions can regulate the expression of genes related to environmental responses, indicating their potential role in adaptive evolution. Overall, our study provides insights into NUPT evolution and their influence on gene function and plant adaptability to environmental stimuli.

Plastids↗

PubMed2025

Subgenomic divergence and functional innovation following whole-genome duplication in Maleae species of Rosaceae.

Whole-genome duplication (WGD) drives plant evolution by inducing karyotype rearrangements and gene loss through subgenome fractionation. In this study, we investigate post-WGD evolutionary dynamics in Rosaceae, focusing on Maleae species, which uniquely experienced an additional WGD. Using phylogenetic and synteny analyses, we reveal that chromosomal breakpoints act as hotspots for localized fractionation, contributing to blurred homoeologous origins and influencing gene retention patterns. Here, we reconstruct karyotype evolution across Rosaceae subfamilies, highlighting chromosome reductions and lineage-specific rearrangements in Dryadoideae, Rosoideae, and Amygdaloideae. We also identify a bias for retaining transcription factors and hormone-related genes from older WGDs in subsequent polyploidy events. Transcriptome analysis classifies WGD-derived genes in Maleae species, such as apple and loquat, into three expression groups, with hormone-enriched genes playing roles in lignification and fruit-related innovations. These findings demonstrate the interplay between chromosomal breakpoints, biased retention, and functional divergence, revealing their contributions to genomic and phenotypic evolution in Maleae and their adaptive success within Rosaceae.

Genome, Plant↗

PubMed2025

Haplotype-resolved telomere-to-telomere genome assembly of Populus lasiocarpa unveils retrotransposon-driven centromere evolution.

Centromeres, essential for chromosome segregation, exhibit remarkable evolutionary dynamism in sequence composition and structural organization. Here, we report the first haplotype-resolved, telomere-to-telomere genome assembly of Populus lasiocarpa (PLAS) and precisely map all 38 functional centromeres through CENH3 ChIP-Seq. Unlike classical satellite-rich centromeres in model plants, PLAS centromeres lack abundant satellite arrays but are dominated by retrotransposons, particularly RLG and RIL elements, which form intricate nested TE arrays within the functional centromeric regions, disrupting their structural integrity and driving their evolution. Comparative analysis with P. trichocarpa reveals a conserved retrotransposon-dominated architecture, despite minimal sequence conservation. We propose a cyclic model of centromere evolution in which autonomous retrotransposons destabilize functional centromeres through epigenetic erosion, triggering neocentromere formation at pericentromeric sites enriched in transposable elements (TEs) and tandem repeats (TRs). These neocentromeres either succumb to recurrent retrotransposon invasions or stabilize through KARMA-mediated TR expansion, ultimately giving rise to satellite-rich centromeres. Our work redefines centromeres as dynamic, epigenetically plastic domains shaped by retrotransposon-TR antagonism, challenging the satellite-centric paradigm and offering novel insights into plant genome evolution.

Retroelements↗

PubMed1996

Adaptive evolution of human immunodeficiency virus-type 1 during the natural course of infection.

The rate of progression to disease varies considerably among individuals infected with human immunodeficiency virus-type 1 (HIV-1). Analyses of semiannual blood samples obtained from six infected men showed that a rapid rate of CD4 T cell loss was associated with relative evolutionary stasis of the HIV-1 quasispecies virus population. More moderate rates of CD4 T cell loss correlated with genetic evolution within three of four subjects. Consistent with selection by the immune constraints of these subjects, amino acid changes were apparent within the appropriate epitopes of human leukocyte antigen class I-restricted cytotoxic T lymphocytes. Thus, the evolutionary dynamics exhibited by the HIV-1 quasispecies virus populations under natural selection are compatible with adaptive evolution.

Acquired Immunodeficiency Syndrome↗

PubMed2026

Repeated emergence and fitness heterogeneity of KPC-33 in ST11 Klebsiella pneumoniae under ceftazidime-avibactam pressure.

Ceftazidime-avibactam (CZA) is an important therapeutic option for infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae. However, CZA exposure also selects for emergent KPC variants. Their in vivo evolutionary patterns, fitness consequences, and underlying molecular mechanisms remain unclear. We performed a longitudinal multiomics analysis of 35 clonally related ST11 KPC-producing K. pneumoniae isolates collected from eight hospitalized patients during clinical follow-up, most of whom had received CZA therapy. Whole-genome sequencing, antimicrobial susceptibility testing, in vitro competition assays, enzyme kinetic analysis, and transcriptomic sequencing were used to systematically characterize the within-host evolutionary dynamics of KPC variants and the fitness heterogeneity of KPC-33. Multiple KPC variants were identified during longitudinal follow-up, among which KPC-33 was the most frequently detected. Among the seven patients who received CZA treatment, KPC-33 was detected in longitudinal isolates from four patients. It was also identified in patient P3, who had not received CZA, whereas other variants were only sporadically identified. Biochemical analysis showed that KPC-33 exhibited an altered kinetic profile relative to KPC-2, characterized by reduced catalytic turnover and altered substrate affinity. KPC-33 did not exhibit a uniform and pronounced fitness defect but instead showed marked strain-dependent heterogeneity. Strains with higher competitive fitness generally showed only limited transcriptional changes, whereas those with lower fitness were accompanied by broader transcriptional remodeling. In this longitudinal cohort, KPC-33 was repeatedly detected, predominantly under CZA-associated selective conditions. Its fitness consequences were clearly strain background dependent and may be associated with the extent of transcriptional remodeling. These findings provide new evidence for understanding the in vivo evolution of CZA resistance.

KPC-33↗

PubMed2026

New Insights into Genomic Variations and Mutational Events Associated with Plant-Pathogen Interactions.

Plant diseases threaten global food security, causing up to 40% crop yield losses and more than $220 billion in annual economic damage. This review synthesizes recent advances in understanding the genomic variations and mutational events underlying plant-pathogen interactions and durable plant disease resistance. Key insights into evolutionary dynamics, genetic variability, and coadaptive strategies reveal the complexity of host-pathogen relationships and the implications for developing durable disease resistance. Integrative approaches combining genome-wide association studies and functional genomics have uncovered the polygenic and epistatic architecture of quantitative resistance. Advances in pan-genomics and high-throughput sequencing have revealed extensive genetic variability in cultivated/elite germplasm and wild relatives. Emerging technologies, including gene editing, multi-omics, and machine learning, enable predictive modeling of resistance traits and support evolution that informs plant breeding strategies. Collectively, these advances provide a robust framework for developing durable resistance and sustainable crop protection in the face of global agricultural challenges.

Host-Pathogen Interactions↗

PubMed2026

Potential survival strategies of novel comammox and nitrite-oxidizing Nitrospira synthesizing osmoprotectants in a wastewater microbiome treating high-ammonia brackish landfill leachate.

BACKGROUND: In the late stages of landfill operation, leachate becomes brackish and contains high concentrations of ammonia with limited organic carbon. At leachate treatment facilities, it is typically subjected to nitrification followed by denitrification, with methanol supplied as an external electron donor. This unique environment may harbor novel microorganisms, including nitrifiers. Although a variety of microorganisms are involved in nitrification, their substrate specificity and salinity tolerance remain insufficiently understood. In this study, a genome-centric metagenome analysis was conducted on the microbiome from a leachate treatment facility at a closed landfill. RESULTS: A total of 68 metagenome-assembled genomes (MAGs) were reconstructed, including 64 putative novel species. Among these, two Nitrospira MAGs were recovered: a novel complete ammonia-oxidizing bacterium (comammox), Nitrospira LAS72 (88.72% completeness, 2.10% contamination), and canonical nitrite-oxidizing Nitrospira LAS18 (99.98% completeness, 2.29% contamination). Comparative genomic analysis with 260 publicly available Nitrospira genomes revealed that LAS18 represents a new sub-lineage within lineage VII of the Nitrospira genus. Two ammonia-oxidizing archaea (AOA), Candidatus Nitrosocosmicus LAS21 and Nitrosarchaeum LAS73, were also identified, while canonical ammonia-oxidizing bacteria were not detected. Given the brackish conditions (1.23% salinity) and the methanol-fed operation of the treatment facility, the genomic potential for osmotic stress adaptation and methanol metabolism was investigated. Comammox Nitrospira LAS72 harbors biosynthetic pathways for several compatible solutes (osmoprotectants), including glycine betaine, proline, trehalose, and L-glutamate. Moreover, comammox Nitrospira LAS72 possesses genetic potential for oxidizing formaldehyde, suggesting that it may exploit these methanol-derived intermediates as energy sources. These features indicate that LAS72 may withstand osmotic fluctuations through the production of various osmoprotectants and thrive under the unique conditions of a methanol-fed environment. CONCLUSIONS: The discovery of novel comammox Nitrospira and canonical Nitrospira forming a new sub-lineage within lineage VII of the Nitrospira genus in an ammonia-rich brackish environment provides the first genomic evidence for evolutionary adaptation among nitrifiers to saline, methanol-fed environments. These findings enhance our understanding of the ecological and evolutionary dynamics shaping nitrifier communities in complex treatment ecosystems. Video Abstract.

Ammonia↗

PubMed2025

A metabolic atlas of the Klebsiella pneumoniae species complex reveals lineage-specific metabolism and capacity for intra-species co-operation.

The Klebsiella pneumoniae species complex inhabits a wide variety of hosts and environments, and is a major cause of antimicrobial resistant infections. Genomics has revealed the population comprises multiple species/sub-species and hundreds of distinct co-circulating sub-lineage (SLs) that are associated with distinct gene complements. A substantial fraction of the pan-genome is predicted to be involved in metabolic functions and hence these data are consistent with metabolic differentiation at the SL level. However, this has so far remained unsubstantiated because in the past it was not possible to explore metabolic variation at scale. Here, we used a combination of comparative genomics and high-throughput genome-scale metabolic modeling to systematically explore metabolic diversity across the K. pneumoniae species complex (n = 7,835 genomes). We simulated growth outcomes for each isolate using carbon, nitrogen, phosphorus, and sulfur sources under aerobic and anaerobic conditions (n = 1,278 conditions per isolate). We showed that the distributions of metabolic genes and growth capabilities are structured in the population, and confirmed that SLs exhibit unique metabolic profiles. In vitro co-culture experiments demonstrated reciprocal commensalistic cross-feeding between SLs, effectively extending the range of conditions supporting individual growth. We propose that these substrate specializations may promote the existence and persistence of co-circulating SLs by reducing nutrient competition and facilitating commensal interactions. Our findings have implications for understanding the eco-evolutionary dynamics of K. pneumoniae and for the design of novel strategies to prevent opportunistic infections caused by this World Health Organization priority antimicrobial resistant pathogen.

Klebsiella pneumoniae↗