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PubMed2005

A new strategy to identify novel genes and gene isoforms: Analysis of human chromosomes 15, 21 and 22.

We present here a novel methodology for the identification of genome regions potentially spanning one or more protein coding genes. It is based on the detection of clusters of conserved sequence tags whose evolutionary dynamics, based on the observation of an excess bias of synonymous substitutions at nucleotide level and of conservative replacements at protein level, suggests a likely protein coding role. A benchmark test carried out on a 236 Mbp of human-mouse syntenic regions from human chromosomes 15, 21 and 22 identified 25 CST clusters potentially containing unannotated genes. A further annotation update of the human genome assembly revealed that 11/25 clusters actually contained a total of 20 validated genes and 10 of the remaining 14 clusters had several experimental evidence in support of the presence of protein coding genes. These findings demonstrate the effectiveness and high prediction reliability of the proposed methodology which could specifically be applied to the annotation of novel genome sequences.

Animals↗
PubMed2006

Human Endogenous Retrovirus (HERV)-R family in primates: Chromosomal location, gene expression, and evolution.

Hitherto, full-length endogenous retrovirus (HERV)-R has been located at human chromosome 7q11.2, and mRNA and envelope proteins have been detected in placenta and a variety of other cell types. In the present study, using a probe derived from the gorilla fosmid library, we detected the paralogous locus (7q31.3) of the HERV-R env gene in human chromosome 7q11.2, and also determined the chromosomal location in apes and Old World monkeys. The HERV-R gene was not detected in New World monkeys or prosimians with FISH and PCR analyses. We determined the sequences of the HERV-R env genes obtained from the genomic DNA of primates using PCR and sequencing tools. Except for a HERV-R env sequence derived from gorilla DNA, the functional domains of putative envelope proteins are conserved, suggesting that those domains could have a functional capacity in the primate genome. In addition, we investigated the env gene expression of HERV-R in various human tissues and cancer cells. An RT-PCR approach indicated that the env gene was expressed in several human tissues (brain, prostate, testis, kidney, placenta, thymus, and uterus) and cancer cells (RT4, BT-474, MCF7, OVCAR-3, LOX-IMVI, and AZ521). Taken together, our data could be of great use for understanding the evolutionary dynamics of HERV-R through primate radiation as well as the implications of its functional role in human tissues and cancers cells.

Animals↗
PubMed2006

Different evolutionary fates of recently integrated human and chimpanzee LINE-1 retrotransposons.

The long interspersed element-1 (LINE-1 or L1) is a highly successful retrotransposon in mammals. L1 elements have continued to actively propagate subsequent to the human-chimpanzee divergence, approximately 6 million years ago, resulting in species-specific inserts. Here, we report a detailed characterization of chimpanzee-specific L1 subfamily diversity and a comparison with their human-specific counterparts. Our results indicate that L1 elements have experienced different evolutionary fates in humans and chimpanzees within the past approximately 6 million years. Although the species-specific L1 copy numbers are on the same order in both species (1200-2000 copies), the number of retrotransposition-competent elements appears to be much higher in the human genome than in the chimpanzee genome. Also, while human L1 subfamilies belong to the same lineage, we identified two lineages of recently integrated L1 subfamilies in the chimpanzee genome. The two lineages seem to have coexisted for several million years, but only one shows evidence of expansion within the past three million years. These differential evolutionary paths may be the result of random variation, or the product of competition between L1 subfamily lineages. Our results suggest that the coexistence of several L1 subfamily lineages within a species may be resolved in a very short evolutionary period of time, perhaps in just a few million years. Therefore, the chimpanzee genome constitutes an excellent model in which to analyze the evolutionary dynamics of L1 retrotransposons.

5' Untranslated Regions↗
PubMed2025

Fe-S cluster deficiency drives small colony variant formation in persistent infections.

INTRODUCTION: Small colony variants (SCVs) of Staphylococcus aureus (S. aureus) are associated with persistent infections and poor clinical outcomes. The mechanisms driving stable SCV formation remain poorly understood, particularly concerning metabolic adaptations. This study explores the in-host evolutionary dynamics of S. aureus and identifies a novel genetic determinant linked to SCV formation. OBJECTIVES: To investigate the genetic mutations and phenotypic adaptations underlying SCV formation, with a focus on the role of a novel mutation in the sufB gene, which is critical for Fe-S cluster biosynthesis. METHODS: Sequential isolates from a patient with recurrent infections were analyzed using whole-genome sequencing, antimicrobial susceptibility testing, and functional assays. The phylogenetic relationship of the isolates was determined, and specific mutations were identified. Functional assays included aconitase and glutamate synthase activity measurements, ATP level quantification, reactive oxygen species (ROS) production, and biofilm formation assays. In vivo pathogenesis was assessed using a murine catheter infection model. RESULTS: A novel frameshift mutation in sufB was identified, disrupting Fe-S cluster biosynthesis and impairing the TCA cycle and electron transport chain, leading to reduced ATP and ROS production. This metabolic reprogramming promoted stable SCV formation, characterized by slow growth, enhanced tolerance to antibiotics and neutrophil-mediated killing, and persistent inflammation in vivo. Restoration of sufB reversed these phenotypes, confirming its pivotal role in SCV-associated persistence. CONCLUSION: sufB is a novel genetic determinant of stable SCV formation through Fe-S cluster deficiency, driving metabolic shifts that enhance immune evasion and chronic infection. Our findings highlight antibiotic stewardship and suggest potential therapeutic strategies for managing persistent SCV-associated infections.

Staphylococcus aureus↗
PubMed2025

Genomic mechanism of aroma terpenoids biosynthesis in plants.

BACKGROUND: Aroma terpenoids are crucial plant secondary metabolites with physiological and commercial importance. Interestingly, both closely and distantly related species can synthesize identical aroma terpenoids. With the development of genome sequencing technology, it has become possible to elucidate the genomic mechanism underlying this phenomenon. AIM: This review highlights whole-genome data as a robust strategy for investigating the genomic mechanism of aroma terpenoids biosynthesis in plants, and provides new perspectives on the origin, evolution, and engineering of terpene synthases (TPSs). This aims to significantly benefit plant breeding and enhance suitability for industrial production. KEY SCIENTIFIC CONCEPTS OF REVIEW: Genomic mechanism of aroma terpenoids biosynthesis in plant genomes is the genetic and evolutionary dynamics. We elaborate the genomic mechanism governing the biosynthesis of plant-derived aroma terpenoids in three dimensions: (1) Genome-wide identification and phylogenetic analyses of TPSs. The same aroma terpenoids were produced by numerous plant species with chromosome-level genomes. Based on 34 plant genomes, we identified 1643 TPSs and classified them into seven subfamilies. (2) Functional and structural basis of TPSs. We found that TPSs with identical functions in distant species exhibit low sequence similarity but conserved active cavity architectures. Conversely, functionally distinct TPSs in closely related species cluster phylogenetically but differ in active cavity structures. (3) Patterns of TPS gene origination. Comparative genomic analyses within and between species revealed three patterns enabling TPSs to acquire the same functions: tandem duplications, dispersed duplications, and genes without duplication.

Terpenes↗
PubMed2004

Maximization principles and daisyworld.

We investigate whether the equilibrium time-averaged state of a self-organizing system with many internal degrees of freedom, 2D-daisyworld, can be described by optimizing a single quantity. Unlike physical systems where a principle of maximum energy production has been observed, daisyworld follows evolutionary dynamics rather than Hamiltonian dynamics. We find that this is sufficient to invalidate the maximum entropy production principle, finding instead a different principle, that the system self-organizes to a state which maximizes the amount of life.

Biological Evolution↗
PubMed2004

Some basic properties of immune selection.

We analyze models for the evolutionary dynamics of viral or other infectious agents within a host. We study how the invasion of a new strain affects the composition and diversity of the viral population. We show that--under strain-specific immunity--the equilibrium abundance of uninfected cells declines during viral evolution. In addition, for cytotoxic immunity the absolute force of infection, and for non-cytotoxic immunity the absolute cellular virulence increases during viral evolution. We prove global stability by means of Lyapunov functions. These unidirectional trends of virus evolution under immune selection do not hold for general cross-reactive immune responses, which introduce frequency-dependent selection among viral strains. Therefore, appropriate cross-reactive immunity can lead to a viral evolution within a host which limits the extent of the disease.

Animals↗
PubMed2005

Synergy and discounting of cooperation in social dilemmas.

The emergence and maintenance of cooperation by natural selection is an enduring conundrum in evolutionary biology, which has been studied using a variety of game theoretical models inspired by different biological situations. The most widely studied games are the Prisoner's Dilemma, the Snowdrift game and by-product mutualism for pairwise interactions, as well as Public Goods games in larger groups of interacting individuals. Here, we present a general framework for cooperation in social dilemmas in which all the traditional scenarios can be recovered as special cases. In social dilemmas, cooperators provide a benefit to the group at some cost, while defectors exploit the group by reaping the benefits without bearing the costs of cooperation. Using the concepts of discounting and synergy for describing how benefits accumulate when more than one cooperator is present in a group of interacting individuals, we recover the four basic scenarios of evolutionary dynamics given by (i) dominating defection, (ii) coexistence of defectors and cooperators, (iii) dominating cooperation and (iv) bi-stability, in which cooperators and defectors cannot invade each other. Generically, for groups of three or more interacting individuals further, more complex, dynamics can occur. Our framework provides the first unifying approach to model cooperation in different kinds of social dilemmas.

Animals↗
PubMed2006

Genetic instability and clonal expansion.

Inactivation of tumor suppressor genes can lead to clonal expansion. We study the evolutionary dynamics of this process and calculate the probability that inactivation of a tumor suppressor gene is preceded by mutations in genes that confer genetic instability. Unstable cells might have a slower rate of clonal expansion than stable cells because of an increased probability of generating lethal mutations or inducing apoptosis. We show that the different growth rates of genetically stable and unstable cells during clonal expansion represent, in general, only a small disadvantage for genetic instability. The intuitive reason for this conclusion is that robust clonal expansion, where cellular birth rates are significantly greater than death rates, occurs on a much faster time scale than waiting for those mutations that allow clonal expansion. Moreover, in special cases where clonal expansion is very slow, genetically unstable cells have a higher probability to accumulate additional mutations during clonal expansion that confer a selective advantage. Clonal expansion represents a major disadvantage for genetic instability only when inactivation of the tumor suppressor gene leads to a very small increase of the cellular reproductive rate that is cancelled by the increased mortality of unstable cells.

Animals↗
PubMed2006

Selection for mutational robustness in finite populations.

We investigate the evolutionary dynamics of a finite population of RNA sequences replicating on a neutral network. Despite the lack of differential fitness between viable sequences, we observe typical properties of adaptive evolution, such as increase of mean fitness over time and punctuated-equilibrium transitions, after initial mutation-selection balance has been reached. We find that a product of population size and mutation rate of approximately 30 or larger is sufficient to generate selection pressure for mutational robustness, even if the population size is orders of magnitude smaller than the neutral network on which the population resides. Our results show that quasispecies effects and neutral drift can occur concurrently, and that the relative importance of each is determined by the product of population size and mutation rate.

Animals↗
PubMed2006

The evolution of altruism: game theory in multilevel selection and inclusive fitness.

Although the prisoner's dilemma (PD) has been used extensively to study reciprocal altruism, here we show that the n-player prisoner's dilemma (NPD) is also central to two other prominent theories of the evolution of altruism: inclusive fitness and multilevel selection. An NPD model captures the essential factors for the evolution of altruism directly in its parameters and integrates important aspects of these two theories such as Hamilton's rule, Simpson's paradox, and the Price covariance equation. The model also suggests a simple interpretation of the Price selection decomposition and an alternative decomposition that is symmetrical and complementary to it. In some situations this alternative shows the temporal changes in within- and between-group selection more clearly than the Price equation. In addition, we provide a new perspective on strong vs. weak altruism by identifying their different underlying game structures (based on absolute fitness) and showing how their evolutionary dynamics are nevertheless similar under selection (based on relative fitness). In contrast to conventional wisdom, the model shows that both strong and weak altruism can evolve in periodically formed random groups of non-conditional strategies if groups are multigenerational. An integrative approach based on the NPD helps unify different perspectives on the evolution of altruism.

Altruism↗
PubMed2026

Convergence and global molecular epidemiology of Klebsiella pneumoniae plasmids harbouring the iuc3 virulence locus: a population genomic analysis.

BACKGROUND: Klebsiella pneumoniae is an important pathogen of humans and animals. In the past five years, increasing reports of convergent strains that carry both virulence factors and antimicrobial resistance genes (ARGs) have raised serious public health concerns. The aim of this study is to describe the global diversity of plasmids carrying iuc3 (a key virulence factor in K pneumoniae associated with pigs and clinical isolates) from diverse settings, and their role in the emergence of convergent strains through hybridisation with plasmids carrying ARGs. METHODS: This population genomic analysis study was designed to describe both the global and local diversity of iuc3-carrying plasmids from diverse sources, and the co-occurrence of iuc3 with ARGs. We used all 4148 Klebsiella spp isolates from two large One-Health studies (SpARK, Italy, and OH-DART, Thailand), including 191 Klebsiella isolates from pigs, 635 from clinical isolates, 1040 from hospital and community carriage, and 2282 from other sources. Short-read sequencing of Klebsiella isolates was performed as part of the SpARK study. We sequenced Klebsiella isolates from the OH-DART (MicrobesNG, Birmingham, UK; HiSeq and NovaSeq, Illumina San Diego, CA, USA; GridION, Oxford Nanopore Technologies, Oxford, UK) and SpARK (MinION or GridION, Oxford Nanopore Technologies, Oxford, UK) studies. We also retrieved plasmid sequences carrying iuc3 from the National Centre for Biotechnology Information (NCBI). To ascertain the degree of diversity, evolutionary dynamics, and structuring across ecological and geographical axes, we detected ARGs and virulence loci, analysed clustering patterns and generated approximate maximum-likelihood phylogenetic trees. FINDINGS: We identified 48 K pneumoniae isolates with iuc3 in the SpARK data and 79 in the OH-DART data. Three (2·4%) of these 127 isolates were from clinical sources, 73 (57·5%) were from pig or pork meat. iuc3 isolates corresponded to multiple (n=47) host sequence types (STs), with ST35, ST45, ST881, ST25, and ST967 harbouring iuc3 in both datasets. We generated hybrid assemblies for 44 (SpARK) and 36 (OH-DART) isolates, plus a single iuc3 isolate from Germany. 53 (65·4%) of these isolates were from pigs, three (3·7%) from clinical sources, and 25 (30·9%) from other sources. There were an additional 48 iuc3 positive isolates from our collections for which only short read data was available. A single iuc3-positive Klebsiella oxytoca isolate from a pig farm was detected in the SpARK data, which was also sequenced. We identified 330 iuc3-positive isolates and 58 iuc3-carrying plasmid assemblies from NCBI, of which 83 (21·4%) were from clinical sources, 120 from pigs (30·9%), and 185 (47·7%) from other sources or of unknown provenance. These isolates were from K pneumoniae except two isolates of Klebsiella quasipneumoniae subsp similipneumoniae and one of Enterobacter hormaechei. The combined dataset of 517 iuc3 plasmids ranged in size from 110 375 bp to 365 580 bp and mostly corresponded to multiple IncFIB(K) and IncFII replicon types. We found seven convergent K pneumoniae plasmids in the Thai data: six from fresh markets and one from a neighbouring hospital. These plasmids emerged through the hybridisation of cocirculating iuc3 plasmids and plasmids encoding extended-spectrum β-lactamases (ESBLs), although none of these seven plasmids carried genes encoding carbapenemases. We also identified putative cocirculating parental plasmids carrying iuc3 and ESBL-encoding genes. Clustering and phylogenetic analysis resolved the iuc3 plasmid sequences into three groups, which were consistent using both complete plasmid sequences (n=139) and short-read data (n=517). In the complete plasmid sequence data, 66 strains contained group 1 plasmids, 38 strains contained group 2 plasmids, and 35 strains contained group 3 plasmids. Group 3 plasmids are mostly carried by isolates circulating in hospitals throughout Asia, with occasional examples in Europe and elsewhere, and carry multiple ARGs and potential virulence factors. By contrast, group 1 plasmids are commonly carried by porcine isolates in Europe, and group 2 are a heterogeneous mixture of geographical and ecological sources. INTERPRETATION: Plasmid hybridisation occurs frequently outside of the health-care environment and can lead to the convergence of resistance and virulence traits. Generating complete plasmid sequences from regional population-scale samples facilitates the identification of convergent plasmids and their putative parental plasmids. Three robust groups of iuc3 plasmids were resolved, which show both epidemiological and geographical differences; one of these groups was associated with clinical isolates in Asia and warrants targeted plasmid surveillance. FUNDING: UKRI, JPIAMR, Evolution Education Trust, and a Schlumberger Foundation Fellowship.

Plasmids↗
PubMed2006

Host sex and parasite genetic diversity.

Is the genetic diversity of parasites infecting male and female hosts equal or different? This is the question we address in this paper by studying the neutral genetic variability of the plathyhelminth trematode Schistosoma mansoni within males and females of its natural murine host Rattus rattus in the marshy forest focus of Guadeloupe (French West Indies). Using seven microsatellite markers, we demonstrate that parasites from male hosts are genetically more diversified than parasites from female hosts. Three hypotheses are discussed that could explain this pattern: 1) a host sex-specific duration of cercariae recruitment; 2) a difference in the behaviour of male and female hosts that would lead to the exposure of males to a greater diversity of parasites; and 3) a host sex-biased immunocompetence that would lead to the selection of more genetically diversified individuals in male than in female rats. This finding is the first empirical evidence that each host sex may play different roles in the maintenance of parasite genetic diversity and so in their evolutionary dynamics and epidemiology.

Animals↗
PubMed2026

Molecular characteristics, phylodynamics, and evolutionary changes of avian infectious bronchitis virus detected from chickens in Yunnan Province, 2021-2024.

Avian infectious bronchitis virus (IBV) is endemic in poultry flocks worldwide, posing a significant threat to the global poultry industry. Frequent mixing of free-range local chickens with introduced chickens in Yunnan Province, China, facilitates the transmission, recombination, and mutation of avian IBV, thereby complicating disease prevention and control. In this study, we aimed to investigate the presence of IBV in poultry populations in Yunnan Province. Samples were collected from live poultry markets (LPMs) and breeding farms, comprising 725 randomly sampled cloacal/fecal swabs and 55 tissue samples. IBV-positive samples were confirmed via polymerase chain reaction (PCR), with an overall positivity rate of 0.89% (7/780) for all tested samples. The positivity rate was 0.35% (2/564) in Kunming, 3.7% (2/54) in Zhaotong, 20% (1/5) in Yuxi, and 12.5% (2/16) in Baoshan, while no IBV was detected in samples from Lanping, Xichou, or Ninglang. Six IBV strains, including five GI-19 strains and one GVI-1 strain, were successfully isolated. Phylogenetic analysis further showed that the Yunnan GI-19 strains predominantly clustered with strains originating from Sichuan Province. Sequencing of the S1 gene revealed several amino acids substitutions per isolate in hypervariable regions HVR1-HVR3. Notably, a valine (V) and glycine (G) insertion between amino acid positions 88 and 89 was identified exclusively in isolate F210, a feature rarely reported in IBV. Protein-protein docking analysis indicated that the unique 88-89 insertion in isolate F210 S1 may alter its binding interactions with the host receptor ANPEP. Whole-genome comparison revealed that isolate YX3 shared 97.05% nucleotide identity with strain CK/CH/GX/YL17/2017 from Guangxi, whereas isolates Q47, F13, and F210 shared 96.40%-97.27% identity with strain CK/Henan/H1036/2021 from Henan. Recombination analysis detected obvious recombination events in isolates F13, F210, Q47, and YX3, with GI-22 strains serving as the major parental donors. These genetic characteristics, recombination patterns, and structural insights demonstrate the complex evolutionary dynamics of circulating IBV strains in Yunnan. Continuous molecular epidemiological surveillance combined with functional protein analysis is essential to monitor emerging variants and formulating targeted, effective disease control strategies.

Avian infectious bronchitis virus↗
PubMed2004

Data mining of Mycobacterium tuberculosis complex genotyping results using mycobacterial interspersed repetitive units validates the clonal structure of spoligotyping-defined families.

Recently, a combination of spoligotyping and bioinformatics was proposed as a potential tool for defining major circulating clades of tuberculosis bacilli. In the present study, we attempted to validate the above mentioned classification using a new high-throughput marker, named mycobacterial interspersed repetitive units (MIRUs). Using 12 MIRU loci and spoligotyping, we performed data mining of results on clinical isolates of the Mycobacterium tuberculosis complex representative of global mycobacterial allelic diversity. Knowledge rules permitting automatic labeling of major M. tuberculosis families were defined. Using this strategy, MIRU 24 appeared to be most appropriate for classifying our dataset. The Bovis family was shown to be perfectly classified by a maximum of 3 MIRUs, followed by Africanum and East African Indian (EAI) families by 4 MIRUs, the Beijing family by 6 MIRUs, Haarlem and X families by 8 MIRUs, the T family by 9, and the Latin-American and Mediterranean (LAM) family by 10 MIRUs. Considering the hierarchy of family divergence, our results corroborate a recent suggestion that EAI is the ancestral family followed by Africanum and Bovis. On the other hand, T, X, LAM and Haarlem families appear to be of more recent evolution. These results indicate that data mining of MIRUs is a valuable new tool for analyzing the evolutionary dynamics of the M. tuberculosis complex, and for monitoring an infectious disease such as tuberculosis.

Bacterial Typing Techniques↗
PubMed2005

Emergence and prevention of resistance against small molecule inhibitors.

Small molecule inhibitors target specific metabolic pathways in tumor cells and are a promising class of drugs for the treatment of cancers. The best known example is the treatment of chronic myeloid leukemia (CML) with Gleevec. This is a small molecule inhibitor of the Bcr-Abl kinase which has been shown to drive the initiation and progression of CML. While treatment of early stage CML with Gleevec has been quite successful, later stages of the disease (blast crisis) are not successfully treated due to the emergence of drug resistant cells. It is therefore important to understand the principles according to which drug resistant cells evolve, so that we can design treatment strategies which aim to prevent the rise of resistant cells. Such evolutionary dynamics can be studied with mathematical models, and this article reviews such an approach. We address three specific questions: (i) Do resistant cells emerge before or after the start of therapy? (ii) How does the turnover rate of cancer cells influence the evolution of drug resistant cells? (iii) Can combination therapy be used to prevent drug resistance? We apply our model to the treatment of CML with Gleevec, in order to demonstrate how this mathematical framework can be applied to the treatment of a specific cancer with small molecule inhibitors.

Antineoplastic Agents↗
PubMed2006

Lengsin is a survivor of an ancient family of class I glutamine synthetases re-engineered by evolution for a role in the vertebrate lens.

Lengsin is a major protein of the vertebrate eye lens. It belongs to the hitherto purely prokaryotic GS I branch of the glutamine synthetase (GS) superfamily, but has no enzyme activity. Like the taxon-specific crystallins, Lengsin is the result of the recruitment of an ancient enzyme to a noncatalytic role in the vertebrate lens. Cryo-EM and modeling studies of Lengsin show a dodecamer structure with important similarities and differences with prokaryotic GS I structures. GS homology regions of Lengsin are well conserved, but the N-terminal domain shows evidence of dynamic evolutionary changes. Compared with birds and fish, most mammals have an additional exon corresponding to part of the N-terminal domain; however, in human, this is a nonfunctional pseudoexon. Genes related to Lengsin are also present in the sea urchin, suggesting that this branch of the GS I family, supplanted by GS II enzymes in vertebrates, has an ancient role in metazoans.

Amino Acid Sequence↗
PubMed2004

Nutrient enrichment and food chains: can evolution buffer top-down control?

We show how evolutionary dynamics can alter the predictions of classical models of the effects of nutrient enrichment on food webs. We compare an ecological nutrient-plant-herbivore food-chain model without evolution with the same model, including herbivore evolution, plant evolution, or both. When only herbivores are allowed to evolve, the predictions are similar to those of the ecological model without evolution, i.e., plant biomass does not change with nutrient addition. When only plants evolve, nutrient enrichment leads to an increase in the biomass of all compartments. In contrast, when plants and herbivores are allowed to coevolve, although these two classical patterns are common, a wide variety of other responses is possible. The form of the trade-offs that constrain evolution of the two protagonists is then critical. This stresses the need for experimental data on phenotypic traits, their costs and their influence on the interactions between organisms and the rest of the community.

Adaptation, Biological↗