14 research outputs found
Understanding the evolution of immune genes in jawed vertebrates
Driven by co-evolution with pathogens, host immunity continuously adapts to optimize defence against pathogens within a given environment. Recent advances in genetics, genomics and transcriptomics have enabled a more detailed investigation into how immunogenetic variation shapes the diversity of immune responses seen across domestic and wild animal species. However, a deeper understanding of the diverse molecular mechanisms that shape immunity within and among species is still needed to gain insight into—and generate evolutionary hypotheses on—the ultimate drivers of immunological differences. Here, we discuss current advances in our understanding of molecular evolution underpinning jawed vertebrate immunity. First, we introduce the immunome concept, a framework for characterizing genes involved in immune defence from a comparative perspective, then we outline how immune genes of interest can be identified. Second, we focus on how different selection modes are observed acting across groups of immune genes and propose hypotheses to explain these differences. We then provide an overview of the approaches used so far to study the evolutionary heterogeneity of immune genes on macro and microevolutionary scales. Finally, we discuss some of the current evidence as to how specific pathogens affect the evolution of different groups of immune genes. This review results from the collective discussion on the current key challenges in evolutionary immunology conducted at the ESEB 2021 Online Satellite Symposium: Molecular evolution of the vertebrate immune system, from the lab to natural populations.Biotechnology and Biological Sciences
Research CouncilGrant/Award Number:
BB/K004468/1, BB/M011224/1, BB/
N023803/1 and BB/V000756/1Department for Environment, Food and
Rural AffairsUK Government, Grant/
Award Number: OD0221Deutsche
Forschungsgemeinschaft, Grant/
Award Number: 437857095Grantová
Agentura České Republiky, Grant/Award
Number: 19-20152YGrantová Agentura,
Univerzita Karlova, Grant/Award Number:
646119H2020 European Research
Council, Grant/Award Number: ERC-2019-
StG-
853272-
PALAEOFARMUniversity of Oxford, Grant/Award
Number: 0005172; Ministerstvo Å kolstvÃ,
Mládeže a TělovýchovyGrant/Award
Number: SVV 260684/2023; Ministerstvo
ZemÄ›dÄ›lstvÃ, Grant/Award Number: MZE-RO0723National Institutes of Health,
Grant/Award Number: 1R01AI123659-01A1;
Univerzita Karlova v PrazeGrant/Award Number: START/SCI/113
with reg. no. CZ.02.2.69/0.0/0.0/19_;
Vetenskapsrådet, Grant/Award Number:
2020-0428
The Geographic Pattern and Socioecological Factors of Helicobacter Pylori Infections in the United States
AbstractHelicobacter pylori (H. pylori) is one of the most common human pathogens and may play a role in the development of several distinct diseases, which include gastric ulcer, duodenal ulcer, and gastric cancer. Studying geographic territories of the United States may reveal clusters with high rates of H. pylori infection and perhaps the prevalence of gastric cancer; however, geographic mapping of patterns in the United States is scarce. The purpose of this study was to investigate changes in H pylori infection patterns in the United States between two different time points (2000–2002 and 2016–2018). The primary hypotheses of this study concerned whether socioecological predictors were associated with any regional changes in H. pylori infection patterns. Data on H pylori cases were obtained from the National Inpatient Sample, which represents a 20% stratified sample of U.S. community hospitals and, at the time of data collection, contained data from 10 million inpatient stays in 46 states. Chi-square analyses and multiple logistic regression were used to calculate odds ratios, p-values, and confidence intervals. Although the rates of H. pylori infections did not change over time, there was a regional change in the distribution of infections from the South to the Northeast regions of the United States. H. pylori infections were most prevalent in females less than 55 years of age, and race was not a significant predictor. Medicare and Medicaid usage increased between 2016 and 2018. This study revealed the extent of H. pylori infection in the U.S. and identified socioecological factors that influence its occurrence. This information may help medical and public health professionals and community leaders to create programs and policies to improve infectious outcomes
Understanding the evolution of immune genes in jawed vertebrates
Driven by co-evolution with pathogens, host immunity continuously adapts to optimize defence against pathogens within a given environment. Recent advances in genetics, genomics and transcriptomics have enabled a more detailed investigation into how immunogenetic variation shapes the diversity of immune responses seen across domestic and wild animal species. However, a deeper understanding of the diverse molecular mechanisms that shape immunity within and among species is still needed to gain insight into-and generate evolutionary hypotheses on-the ultimate drivers of immunological differences. Here, we discuss current advances in our understanding of molecular evolution underpinning jawed vertebrate immunity. First, we introduce the immunome concept, a framework for characterizing genes involved in immune defence from a comparative perspective, then we outline how immune genes of interest can be identified. Second, we focus on how different selection modes are observed acting across groups of immune genes and propose hypotheses to explain these differences. We then provide an overview of the approaches used so far to study the evolutionary heterogeneity of immune genes on macro and microevolutionary scales. Finally, we discuss some of the current evidence as to how specific pathogens affect the evolution of different groups of immune genes. This review results from the collective discussion on the current key challenges in evolutionary immunology conducted at the ESEB 2021 Online Satellite Symposium: Molecular evolution of the vertebrate immune system, from the lab to natural populations
Evolutionary genomics : statistical and computational methods
This open access book addresses the challenge of analyzing and understanding the evolutionary dynamics of complex biological systems at the genomic level, and elaborates on some promising strategies that would bring us closer to uncovering of the vital relationships between genotype and phenotype. After a few educational primers, the book continues with sections on sequence homology and alignment, phylogenetic methods to study genome evolution, methodologies for evaluating selective pressures on genomic sequences as well as genomic evolution in light of protein domain architecture and transposable elements, population genomics and other omics, and discussions of current bottlenecks in handling and analyzing genomic data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and expert implementation advice that lead to the best results. Authoritative and comprehensive, Evolutionary Genomics: Statistical and Computational Methods, Second Edition aims to serve both novices in biology with strong statistics and computational skills, and molecular biologists with a good grasp of standard mathematical concepts, in moving this important field of study forward
Chimera Ligand for Pili and Lectin A Protein Controls Antibiotic-Promoted Biofilm Formation, Swarming Motility, Tolerance and Persister Formation by Pseudomonas aeruginosa
Throughout the human history, the fight against bacterial infections had never stopped but the remedies for bacterial infections were often insufficient and for many infectious diseases, there was no treatment available. The revolution in antimicrobial infection therapy began with the discovery of penicillin by Alexander Fleming in 1928. However, since the first introduction of antibiotics, bacteria over time have evolved sophisticated resistant strains against almost all the available antibiotics which cause selection pressure on the bacteria to evolve their genetic makeup and develop resistance against such agents. Furthermore, bacteria can form surface attached multicellular communities known as biofilms. Bacteria residing within biofilms are protected by biofilms which renders the bacteria more difficult to eliminate because of the low permeability of antibiotics through outer membranes. Combating such resistant bacteria is an extremely difficult task if using antibiotics alone. Hence scientific community continuously seeks new strategies to overpower these resistant bacteria.
The focus of the research work presented here is to develop a class of chimera ligands that can bind to both pili and LecA protein of Pseudomonas aeruginosa to inhibit both swarming motility and biofilm formation. The potential adjuvant agents of these chimera ligands that can increase the effectiveness of antibiotics were demonstrated. In addition, the ability of our adjuvant molecules to eliminate drug-tolerant bacteria and to reduce persisters, in combination with antibiotics was demonstrated.
The binding property of chimera ligands was demonstrated by competitive fluorescence polarization assay (LecA) and by adding a functional group to a ligand that can covalently attach to the receptor protein only when the physical ligand-receptor binding takes place (Pili). In addition, the effect of externally added pili on the swarming motility of Pseudomonas aeruginosa was tested to support the mechanistic study of the pili as the receptor (or one of the receptors) that will bind to rhamnolipids and our synthetic agents, and upon binding, causing the bacterial activities.
For quantification of polysaccharides, two efficient detection and quantification methods that make use of the negative charges of the alginate polymer and do not involve degradation of the targeted polysaccharide were described. Both approaches provide efficient methods for monitoring alginate production by mucoid Pseudomonas aeruginosa.
The effect of a class of synthetic analogs of rhamnolipids at controlling (promoting and inhibiting) the biofilm formation activities of a non-rhamnolipid-producing strain – rhlA – of Pseudomonas aeruginosa was demonstrated. The bioactive synthetic analogs of rhamnolipids promote biofilm formation by rhlA mutant at low concentrations but inhibit the biofilm formation at high concentrations. To explore the internal structures formed by the biofilms, the wild-type biofilms formed with substantial topography (hills and valleys) when the sample is under shaking conditions were observed by confocal microscope. Using this observation as a comparison, the effect of synthetic analogs of rhamnolipids on promoting structured (porous) biofilm of rhlA mutant, at intermediate concentrations between the low ones that promoted biofilm formation and the high ones that inhibited biofilm formation was demonstrated. This study suggests a potential chemical signaling approach to control multiple bacterial activities
The role of visual adaptation in cichlid fish speciation
D. Shane Wright (1) , Ole Seehausen (2), Ton G.G. Groothuis (1), Martine E. Maan (1) (1) University of Groningen; GELIFES; EGDB(2) Department of Fish Ecology & Evolution, EAWAG Centre for Ecology, Evolution and Biogeochemistry, Kastanienbaum AND Institute of Ecology and Evolution, Aquatic Ecology, University of Bern.In less than 15,000 years, Lake Victoria cichlid fishes have radiated into as many as 500 different species. Ecological and sexual sel ection are thought to contribute to this ongoing speciation process, but genetic differentiation remains low. However, recent work in visual pigment genes, opsins, has shown more diversity. Unlike neighboring Lakes Malawi and Tanganyika, Lake Victoria is highly turbid, resulting in a long wavelength shift in the light spectrum with increasing depth, providing an environmental gradient for exploring divergent coevolution in sensory systems and colour signals via sensory drive. Pundamilia pundamila and Pundamilia nyererei are two sympatric species found at rocky islands across southern portions of Lake Victoria, differing in male colouration and the depth they reside. Previous work has shown species differentiation in colour discrimination, corresponding to divergent female preferences for conspecific male colouration. A mechanistic link between colour vision and preference would provide a rapid route to reproductive isolation between divergently adapting populations. This link is tested by experimental manip ulation of colour vision - raising both species and their hybrids under light conditions mimicking shallow and deep habitats. We quantify the expression of retinal opsins and test behaviours important for speciation: mate choice, habitat preference, and fo raging performance
Molecular Evolution of Hominoid Primates: Phylogeny and Regulation
The complete mtDNA of one eastern gorilla was sequenced to provide the most accurate date for the mitochondrial divergence of gorillas. The most recent common ancestor of eastern lowland and western lowland gorillas existed about 1.9 million years ago, slightly more recent than that of chimpanzee and bonobo. This study also depicts that the eastern and western gorillas show species level genetic divergence.
Hominoid mating systems differ tremendously. The level of sperm competition varies according to the mating system, which presumably imposes unique selective pressures on the seminal proteins of each species. Cartilage acidic protein 1 (CRTAC1) was identified in our lab as the protein with the largest difference in abundance between human and chimpanzee, being found at 142-fold higher in chimpanzee. The coding region of CRTAC1 is extremely conserved with signature of strong purifying selection. Paradoxically, CRTAC1 `promoter\u27 from human drives transcription significantly greater than chimpanzee, with or without androgen stimulation. Analyzing H3K27Ac data, a ~2.2kb region was identified as a possible additional cis-regulatory element. The cis-regulatory region behaved like a silencer and aided in strong transcriptional repression in humans. Although its underlying basis remains elusive, it can be speculated that the differential expression of CRTAC1 between human and chimpanzee seminal plasma results from tissue specific over/under expression of this gene.
The unique gains and losses of miRNAs within hominoids have remained understudied. The overall goal of this project was to identify the uniquely gained and lost miRNAs and their targets within hominoids. I found 14 miRNAs uniquely gained in humans. Maximum uniquely gained and lost miRNAs were found to be brain specific. The targets of uniquely gained miRNAs in human are also associated with brain-associated functions. Older miRNAs were found to be more conserved compared to the newer miRNAs gained \u3c15 Mya