scholarly journals Metagenomic targets of balancing selection in the human gut

2021 ◽  
Author(s):  
Andrew H. Moeller
Keyword(s):  
Allelic Variation ◽  
Balancing Selection ◽  
Bacterial Species ◽  
Allelic Diversity ◽  
Metagenomic Data ◽  
Adaptive Landscape ◽  
Multidrug Efflux ◽  
Human Gut ◽  
D Values ◽  
Tajima’S D

Bacteria in the human gut contend with numerous fluctuating environmental variables, including bouts of extreme selective agents like antibiotics. Theory predicts that oscillations in the adaptive landscape can impose balancing selection on bacterial populations, leaving characteristic signatures in the sequence variation of functionally significant genomic loci. Despite their potential importance for gut bacterial adaptation, the metagenomic targets of balancing selection have not been identified. Here, I present population genetic evidence that balancing selection maintains allelic diversity in multidrug efflux pumps of multiple predominant bacterial species in the human gut metagenome. Metagenome wide scans of 566,958 core open reading frames (CORFs) from 287 bacterial species represented by 118,617 metagenome assembled genomes (MAGs) indicated that most CORFs have been conserved by purifying selection. However, dozens of CORFs displayed positive Tajima’s D values that deviated significantly from their species’ genomic backgrounds, indicating the action of balancing selection. The AcrB subunit of a multidrug efflux pump (MEP) in Bacteroides dorei displayed the highest Tajima’s D of any CORF, and AcrB and other MEPs from a diversity of bacterial species were significantly enriched among the CORFs with the highest Tajima’s D values. Crystal structures indicated that the regions under balancing selection bind tetracycline and macrolide antibiotics. Other proteins identified as targets of balancing selection included synthases, hydrolases, and ion transporters. Intriguingly, bacterial species experiencing balancing selection were the most abundant in the human gut based on metagenomic data, further suggesting fitness benefits of the allelic variation identified.

scholarly journals In silico characterisation of putative Plasmodium falciparum vaccine candidates in African malaria populations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
O. Ajibola ◽  
M. F. Diop ◽  
A. Ghansah ◽  
L. Amenga-Etego ◽  
L. Golassa ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Vaccine ◽  
Transmembrane Domain ◽  
Vaccine Development ◽  
Balancing Selection ◽  
Immune Recognition ◽  
African Countries ◽  
Vaccine Candidates ◽  
D Values ◽  
Tajima’S D

AbstractGenetic diversity of surface exposed and stage specific Plasmodium falciparum immunogenic proteins pose a major roadblock to developing an effective malaria vaccine with broad and long-lasting immunity. We conducted a prospective genetic analysis of candidate antigens (msp1, ama1, rh5, eba175, glurp, celtos, csp, lsa3, Pfsea, trap, conserved chrom3, hyp9, hyp10, phistb, surfin8.2, and surfin14.1) for malaria vaccine development on 2375 P. falciparum sequences from 16 African countries. We described signatures of balancing selection inferred from positive values of Tajima’s D for all antigens across all populations except for glurp. This could be as a result of immune selection on these antigens as positive Tajima’s D values mapped to regions with putative immune epitopes. A less diverse phistb antigen was characterised with a transmembrane domain, glycophosphatidyl anchors between the N and C- terminals, and surface epitopes that could be targets of immune recognition. This study demonstrates the value of population genetic and immunoinformatic analysis for identifying and characterising new putative vaccine candidates towards improving strain transcending immunity, and vaccine efficacy across all endemic populations.

scholarly journals Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage

2017 ◽  
Vol 114 (5) ◽  
pp. 1075-1080 ◽  
Author(s):  
Sonja Lehtinen ◽  
François Blanquart ◽  
Nicholas J. Croucher ◽  
Paul Turner ◽  
Marc Lipsitch ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Balancing Selection ◽  
Bacterial Species ◽  
Allelic Diversity ◽  
Antibiotic Consumption ◽  
Resistance Locus ◽  
Partial Explanation ◽  
Fitness Advantage ◽  
Long Duration ◽  
Resistant Strains

Understanding how changes in antibiotic consumption affect the prevalence of antibiotic resistance in bacterial pathogens is important for public health. In a number of bacterial species, includingStreptococcus pneumoniae, the prevalence of resistance has remained relatively stable despite prolonged selection pressure from antibiotics. The evolutionary processes allowing the robust coexistence of antibiotic sensitive and resistant strains are not fully understood. While allelic diversity can be maintained at a locus by direct balancing selection, there is no evidence for such selection acting in the case of resistance. In this work, we propose a mechanism for maintaining coexistence at the resistance locus: linkage to a second locus that is under balancing selection and that modulates the fitness effect of resistance. We show that duration of carriage plays such a role, with long duration of carriage increasing the fitness advantage gained from resistance. We therefore predict that resistance will be more common in strains with a long duration of carriage and that mechanisms maintaining diversity in duration of carriage will also maintain diversity in antibiotic resistance. We test these predictions inS. pneumoniaeand find that the duration of carriage of a serotype is indeed positively correlated with the prevalence of resistance in that serotype. These findings suggest heterogeneity in duration of carriage is a partial explanation for the coexistence of sensitive and resistant strains and that factors determining bacterial duration of carriage will also affect the prevalence of resistance.

scholarly journals Ultrafast and accurate 16S microbial community analysis using Kraken 2

2020 ◽  
Author(s):  
Jennifer Lu ◽  
Steven L Salzberg
Keyword(s):  
16S Rrna ◽  
Ribosomal Rna ◽  
Bacterial Species ◽  
Community Analysis ◽  
Microbial Community Analysis ◽  
Metagenomic Data ◽  
Human Gut ◽  
Shotgun Metagenomics ◽  
Primary Means ◽  
Unknown Composition

AbstractFor decades, 16S ribosomal RNA sequencing has been the primary means for identifying the bacterial species present in a sample with unknown composition. One of the most widely-used tools for this purpose today is the QIIME (Quantitative Insights Into Microbial Ecology) package. Recent results have shown that the newest release, QIIME 2, has higher accuracy than QIIME, MAPseq, and mothur when classifying bacterial genera from simulated human gut, ocean, and soil metagenomes, although QIIME 2 also proved to be the most computationally expensive method. Kraken, first released in 2014, has been shown to provide exceptionally fast and accurate classification for shotgun metagenomics sequencing projects. Bracken, released in 2016, then provided users with the ability to accurately estimate species or genus abundances using Kraken classification results. Kraken 2, which matches the accuracy and speed of Kraken 1, now supports 16S rRNA databases, allowing for direct comparisons to QIIME and similar systems. Here we show that, using the same simulated 16S rRNA metagenomic data as previous studies, Kraken 2 and Bracken are up to 300 times faster and also more accurate at 16S profiling than QIIME 2.

scholarly journals Genetic diversity of C4 photosynthesis pathway genes in Sorghum bicolor (L.)

2019 ◽  
Author(s):  
Yongfu Tao ◽  
Barbara George-Jaeggli ◽  
Marie Bouteille-Pallas ◽  
Shuaishuai Tai ◽  
Alan Cruickshank ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Sorghum Bicolor ◽  
Gene Family ◽  
Sequence Data ◽  
Allelic Variation ◽  
Balancing Selection ◽  
Allelic Diversity ◽  
Gene Families ◽  
Photosynthetic Pathway ◽  
Sorghum Bicolor L

Abstract Background C 4 photosynthesis has evolved in over 60 different plant taxa and is an excellent example of convergent evolution. Plants using the C 4 photosynthetic pathway have an efficiency advantage, particularly in hot and dry environments. They account for 23% of global primary production and include some of our most productive cereals. While previous genetic studies comparing phylogenetically related C 3 and C 4 species have elucidated the genetic diversity underpinning the C 4 photosynthetic pathway, no previous studies have described the genetic diversity of the genes involved in this pathway within a C 4 crop species. Enhanced understanding of the allelic diversity and selection signatures of genes in this pathway may present opportunities to improve photosynthetic efficiency, and ultimately yield, by exploiting natural variation. Results Here, we present the first genetic diversity survey of 8 known C 4 gene families in an important C 4 crop, Sorghum bicolor (L.) Moench using sequence data of 48 genotypes covering wild and domesticated sorghum accessions. Average nucleotide diversity of C 4 gene families varied more than 20-fold from the NADP-MDH gene family (θπ =0.2×10 -3 ) to the PPDK gene family (θπ = 5.21×10 -3 ). Genetic diversity of C 4 genes was reduced by 22.43% in cultivated sorghum compared to wild and weedy sorghum, indicating that the group of wild and weedy sorghum may constitute an untapped reservoir for alleles related to the C 4 photosynthetic pathway. A SNP-level analysis identified purifying selection signals on C 4 PPDK and CA genes, and balancing selection signals on C 4 PPDK-RP and PEPC genes. Allelic distribution of these C 4 genes was consistent with selection signals detected. Conclusions Domestication of sorghum has reshaped diversity of C 4 pathway. A better understanding of the genetic diversity of this pathway in sorghum paves the way for mining the natural allelic variation for the improvement of photosynthesis.

scholarly journals The capacity to produce hydrogen sulfide (H2S) via cysteine degradation is ubiquitous in the human gut microbiome

2021 ◽  
Author(s):  
Domenick J Braccia ◽  
Xiaofang Jiang ◽  
Mihai Pop ◽  
Brantley Hall
Keyword(s):  
Hydrogen Sulfide ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Therapeutic Interventions ◽  
Metagenomic Data ◽  
Human Gut ◽  
Gut Microbes ◽  
Human Gut Microbiome ◽  
Degrading Bacteria ◽  
H2s Production

As one of the three mammalian gasotransmitters, hydrogen sulfide (H2S) plays a major role in maintaining physiological homeostasis. Endogenously produced H2S plays numerous beneficial roles including mediating vasodilation and conferring neuroprotection. Due to its high membrane permeability, exogenously produced H2S originating from the gut microbiota can also influence human physiology and is implicated in reducing intestinal mucosal integrity and potentiating genotoxicity and is therefore a potential target for therapeutic interventions. Gut microbial H2S production is often attributed to dissimilatory sulfate reducers such as Desulfovibrio and Bilophila species. However, an alternative source for H2S production, cysteine degradation, is present in gut microbes, but the genes responsible for cysteine degradation have not been systematically annotated in gut microbes. To better understand the potential for H2S production via cysteine degradation by the human gut microbiome, we performed a comprehensive search for genes encoding cysteine-degrading genes in 4,644 bacterial genomes from the Unified Human Gastrointestinal Genome (UHGG) catalogue. We identified 407 gut bacterial species as putative cysteine degrading bacteria, 328 of which have not been previously implicated in H2S production. We identified the presence of at least one putative cysteine degrading bacteria in metagenomic data of 100% of 6,644 healthy subjects and the expression of cysteine-degrading genes in metatranscriptomics data of 100% of 59 samples. Additionally, putative cysteine-degrading bacteria are more abundant than sulfate reducing bacteria (p<2.2e-16). Overall, this study improves our understanding of the capacity for H2S production by the human gut microbiome and may help to inform interventions to therapeutically modulate gut microbial H2S production.

scholarly journals Functional Haplotypes and Evolutionary Insight into the Granule-Bound Starch Synthase II (GBSSII) Gene in Korean Rice Accessions (KRICE_CORE)

Foods ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2359
Author(s):  
Thant Zin Maung ◽  
Sang-Ho Chu ◽  
Yong-Jin Park
Keyword(s):  
Balancing Selection ◽  
Phylogenetic Analyses ◽  
Principal Component ◽  
Purifying Selection ◽  
Structural Features ◽  
Genomic Region ◽  
Starch Synthase ◽  
D Values ◽  
Granule Bound Starch Synthase ◽  
Tajima’S D

Granule-bound starch synthase 2 (GBSSII), a paralogous isoform of GBSSI, carries out amylose biosynthesis in rice. Unlike GBSSI, it mainly functions in transient organs, such as leaves. Despite many reports on the starch gene family, little is known about the genetics and genomics of GBSSII. Haplotype analysis was conducted to unveil genetic variations (SNPs and InDels) of GBSSII (OS07G0412100) and it was also performed to gain evolutionary insight through genetic diversity, population genetic structure, and phylogenetic analyses using the KRICE_CORE set (475 rice accessions). Thirty nonsynonymous SNPs (nsSNPs) were detected across the diverse GBSSII coding regions, representing 38 haplotypes, including 13 cultivated, 21 wild, and 4 mixed (a combination of cultivated and wild) varieties. The cultivated haplotypes (C_1–C_13) contained more nsSNPs across the GBSSII genomic region than the wild varieties. Nucleotide diversity analysis highlighted the higher diversity values of the cultivated varieties (weedy = 0.0102, landrace = 0.0093, and bred = 0.0066) than the wild group (0.0045). The cultivated varieties exhibited no reduction in diversity during domestication. Diversity reduction in the japonica and the wild groups was evidenced by the negative Tajima’s D values under purifying selection, suggesting the domestication signatures of GBSSII; however, balancing selection was indicated by positive Tajima’s D values in indica. Principal component analysis and population genetics analyses estimated the ambiguous evolutionary relationships among the cultivated and wild rice groups, indicating highly diverse structural features of the rice accessions within the GBSSII genomic region. FST analysis differentiated most of the classified populations in a range of greater FST values. Our findings provide evolutionary insights into GBSSII and, consequently, a molecular breeding program can be implemented for select desired traits using these diverse nonsynonymous (functional) alleles.

scholarly journals Genetic diversity of C4 photosynthesis pathway genes in Sorghum bicolor (L.)

2019 ◽  
Author(s):  
Yongfu Tao ◽  
Barbara George-Jaeggli ◽  
Marie Bouteille-Pallas ◽  
Shuaishuai Tai ◽  
Alan Cruickshank ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Sorghum Bicolor ◽  
Gene Family ◽  
C4 Photosynthesis ◽  
Allelic Variation ◽  
Balancing Selection ◽  
Allelic Diversity ◽  
Gene Families ◽  
Photosynthetic Pathway ◽  
Sorghum Bicolor L

Abstract Background C4 photosynthesis has evolved in over 60 different plant taxa and is an excellent example of convergent evolution. Plants using the C4 photosynthetic pathway have an efficiency advantage, particularly in hot and dry environments. They account for 23% of global primary production and include some of our most productive cereals. While previous genetic studies comparing phylogenetically related C3 and C4 species have elucidated the genetic diversity underpinning the C4 photosynthetic pathway, no previous studies have described the genetic diversity of the genes involved in this pathway within a C4 crop species. Enhanced understanding of the allelic diversity and selection signatures of genes in this pathway may present opportunities to improve photosynthetic efficiency, and ultimately yield, by exploiting natural variation. Results Here, we present the first genetic diversity survey of 8 known C4 gene families in an important C4 crop, Sorghum bicolor (L.) Moench using sequence data of 48 genotypes covering wild and domesticated sorghum accessions. Average nucleotide diversity of C4 gene families varied more than 20-fold from the NADP-MDH gene family (θπ =0.2×10-3) to the PPDK gene family (θπ = 5.21×10-3). Genetic diversity of C4 genes was reduced by 22.43% in cultivated sorghum compared to wild and weedy sorghum, indicating that the group of wild and weedy sorghum may constitute an untapped reservoir for alleles related to the C4 photosynthetic pathway. A SNP-level analysis identified purifying selection signals on C4 PPDK and CA genes, and balancing selection signals on C4 PPDK-RP and PEPC genes. Allelic distribution of these C4 genes was consistent with selection signals detected.Conclusions Domestication of sorghum has reshaped diversity of C4 pathway. A better understanding of the genetic diversity of this pathway in sorghum paves the way for mining the natural allelic variation for the improvement of photosynthesis.

Substrate use prioritization by a coculture of five species of gut bacteria fed mixtures of arabinoxylan, xyloglucan, β-glucan, and pectin

2020 ◽  
Author(s):  
Y Liu ◽  
AL Heath ◽  
B Galland ◽  
N Rehrer ◽  
L Drummond ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Dietary Fiber ◽  
Plant Cell Wall ◽  
Bacterial Species ◽  
Short Chain ◽  
Emergent Properties ◽  
Human Gut ◽  
Fermentation Products ◽  
Plant Polysaccharides ◽  
Human Gut Microbiota

© 2020 American Society for Microbiology. Dietary fiber provides growth substrates for bacterial species that belong to the colonic microbiota of humans. The microbiota degrades and ferments substrates, producing characteristic short-chain fatty acid profiles. Dietary fiber contains plant cell wall-associated polysaccharides (hemicelluloses and pectins) that are chemically diverse in composition and structure. Thus, depending on plant sources, dietary fiber daily presents the microbiota with mixtures of plant polysaccharides of various types and complexity. We studied the extent and preferential order in which mixtures of plant polysaccharides (arabinoxylan, xyloglucan, β-glucan, and pectin) were utilized by a coculture of five bacterial species (Bacteroides ovatus, Bifidobacterium longum subspecies longum, Megasphaera elsdenii, Ruminococcus gnavus, and Veillonella parvula). These species are members of the human gut microbiota and have the biochemical capacity, collectively, to degrade and ferment the polysaccharides and produce short-chain fatty acids (SCFAs). B. ovatus utilized glycans in the order β-glucan, pectin, xyloglucan, and arabinoxylan, whereas B. longum subsp. longum utilization was in the order arabinoxylan, arabinan, pectin, and β-glucan. Propionate, as a proportion of total SCFAs, was augmented when polysaccharide mixtures contained galactan, resulting in greater succinate production by B. ovatus and conversion of succinate to propionate by V. parvula. Overall, we derived a synthetic ecological community that carries out SCFA production by the common pathways used by bacterial species for this purpose. Systems like this might be used to predict changes to the emergent properties of the gut ecosystem when diet is altered, with the aim of beneficially affecting human physiology. This study addresses the question as to how bacterial species, characteristic of the human gut microbiota, collectively utilize mixtures of plant polysaccharides such as are found in dietary fiber. Five bacterial species with the capacity to degrade polymers and/or produce acidic fermentation products detectable in human feces were used in the experiments. The bacteria showed preferential use of certain polysaccharides over others for growth, and this influenced their fermentation output qualitatively. These kinds of studies are essential in developing concepts of how the gut microbial community shares habitat resources, directly and indirectly, when presented with mixtures of polysaccharides that are found in human diets. The concepts are required in planning dietary interventions that might correct imbalances in the functioning of the human microbiota so as to support measures to reduce metabolic conditions such as obesity.

Clin-mNGS: Automated Pipeline for Pathogen Detection from Clinical Metagenomic Data

2020 ◽  
Vol 15 ◽  
Author(s):  
Akshatha Prasanna ◽  
Vidya Niranjan
Keyword(s):  
Antimicrobial Resistance ◽  
High Performance ◽  
Pathogen Detection ◽  
Bacterial Species ◽  
Workflow Management ◽  
Metagenomic Data ◽  
Antimicrobial Resistance Genes ◽  
Culture Independent ◽  
Automated Pipeline ◽  
User Friendly

Background: Since bacteria are the earliest known organisms, there has been significant interest in their variety and biology, most certainly concerning human health. Recent advances in Metagenomics sequencing (mNGS), a culture-independent sequencing technology have facilitated an accelerated development in clinical microbiology and our understanding of pathogens. Objective: For the implementation of mNGS in routine clinical practice to become feasible, a practical and scalable strategy for the study of mNGS data is essential. This study presents a robust automated pipeline to analyze clinical metagenomic data for pathogen identification and classification. Method: The proposed Clin-mNGS pipeline is an integrated, open-source, scalable, reproducible, and user-friendly framework scripted using the Snakemake workflow management software. The implementation avoids the hassle of manual installation and configuration of the multiple command-line tools and dependencies. The approach directly screens pathogens from clinical raw reads and generates consolidated reports for each sample. Results: The pipeline is demonstrated using publicly available data and is tested on a desktop Linux system and a High-performance cluster. The study compares variability in results from different tools and versions. The versions of the tools are made user modifiable. The pipeline results in quality check, filtered reads, host subtraction, assembled contigs, assembly metrics, relative abundances of bacterial species, antimicrobial resistance genes, plasmid finding, and virulence factors identification. The results obtained from the pipeline are evaluated based on sensitivity and positive predictive value. Conclusion: Clin-mNGS is an automated Snakemake pipeline validated for the analysis of microbial clinical metagenomics reads to perform taxonomic classification and antimicrobial resistance prediction.

scholarly journals Plasmodium vivax Cysteine-Rich Protective Antigen Polymorphism at Exon-1 Shows Recombination and Signatures of Balancing Selection

Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 29
Author(s):  
Lilia González-Cerón ◽  
José Cebrián-Carmona ◽  
Concepción M. Mesa-Valle ◽  
Federico García-Maroto ◽  
Frida Santillán-Valenzuela ◽  
...  
Keyword(s):  
Amino Acid ◽  
B Cell ◽  
Plasmodium Vivax ◽  
Nucleotide Diversity ◽  
Protective Antigen ◽  
Balancing Selection ◽  
Southern Mexico ◽  
Exon 2 ◽  
Exon 1 ◽  
Tajima’S D

Plasmodium vivax Cysteine-Rich Protective Antigen (CyRPA) is a merozoite protein participating in the parasite invasion of human reticulocytes. During natural P. vivax infection, antibody responses against PvCyRPA have been detected. In children, low anti-CyRPA antibody titers correlated with clinical protection, which suggests this protein as a potential vaccine candidate. This work analyzed the genetic and amino acid diversity of pvcyrpa in Mexican and global parasites. Consensus coding sequences of pvcyrpa were obtained from seven isolates. Other sequences were extracted from a repository. Maximum likelihood phylogenetic trees, genetic diversity parameters, linkage disequilibrium (LD), and neutrality tests were analyzed, and the potential amino acid polymorphism participation in B-cell epitopes was investigated. In 22 sequences from Southern Mexico, two synonymous and 21 nonsynonymous mutations defined nine private haplotypes. These parasites had the highest LD-R2 index and the lowest nucleotide diversity compared to isolates from South America or Asia. The nucleotide diversity and Tajima’s D values varied across the coding gene. The exon-1 sequence had greater diversity and Rm values than those of exon-2. Exon-1 had significant positive values for Tajima’s D, β-α values, and for the Z (HA: dN > dS) and MK tests. These patterns were similar for parasites of different origin. The polymorphic amino acid residues at PvCyRPA resembled the conformational B-cell peptides reported in PfCyRPA. Diversity at pvcyrpa exon-1 is caused by mutation and recombination. This seems to be maintained by balancing selection, likely due to selective immune pressure, all of which merit further study.

Sign in / Sign up

Export Citation Format

Share Document