scholarly journals Master Blaster: an approach to sensitive identification of remotely related proteins

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chintalapati Janaki ◽  
Venkatraman S. Gowri ◽  
Narayanaswamy Srinivasan
Keyword(s):  
Evolutionary Divergence ◽  
Homology Detection ◽  
Homologous Proteins ◽  
Scoring Matrices ◽  
A Genome ◽  
Successful Approach ◽  
Family Connections ◽  
And Function ◽  
Related Proteins ◽  
Remote Homologs

AbstractGenome sequencing projects unearth sequences of all the protein sequences encoded in a genome. As the first step, homology detection is employed to obtain clues to structure and function of these proteins. However, high evolutionary divergence between homologous proteins challenges our ability to detect distant relationships. In the past, an approach involving multiple Position Specific Scoring Matrices (PSSMs) was found to be more effective than traditional single PSSMs. Cascaded search is another successful approach where hits of a search are queried to detect more homologues. We propose a protocol, ‘Master Blaster’, which combines the principles adopted in these two approaches to enhance our ability to detect remote homologues even further. Assessment of the approach was performed using known relationships available in the SCOP70 database, and the results were compared against that of PSI-BLAST and HHblits, a hidden Markov model-based method. Compared to PSI-BLAST, Master Blaster resulted in 10% improvement with respect to detection of cross superfamily connections, nearly 35% improvement in cross family and more than 80% improvement in intra family connections. From the results it was observed that HHblits is more sensitive in detecting remote homologues compared to Master Blaster. However, there are true hits from 46-folds for which Master Blaster reported homologs that are not reported by HHblits even using the optimal parameters indicating that for detecting remote homologues, use of multiple methods employing a combination of different approaches can be more effective in detecting remote homologs. Master Blaster stand-alone code is available for download in the supplementary archive.

scholarly journals Ribosome occupancy profiles are conserved between structurally and evolutionarily related yeast domains

2021 ◽  
Author(s):  
Daniel A Nissley ◽  
Anna Carbery ◽  
Mark Chonofsky ◽  
Charlotte M Deane
Keyword(s):  
Amino Acid ◽  
Large Scale ◽  
Sequence Similarity ◽  
Ribosome Profiling ◽  
Supplementary Information ◽  
Rare Codon ◽  
Homologous Proteins ◽  
Translation Speed ◽  
And Function ◽  
Related Proteins

Abstract Motivation Protein synthesis is a non-equilibrium process, meaning that the speed of translation can influence the ability of proteins to fold and function. Assuming that structurally similar proteins fold by similar pathways, the profile of translation speed along an mRNA should be evolutionarily conserved between related proteins to direct correct folding and downstream function. The only evidence to date for such conservation of translation speed between homologous proteins has used codon rarity as a proxy for translation speed. There are, however, many other factors including mRNA structure and the chemistry of the amino acids in the A- and P-sites of the ribosome that influence the speed of amino acid addition. Results Ribosome profiling experiments provide a signal directly proportional to the underlying translation times at the level of individual codons. We compared ribosome occupancy profiles (extracted from five different large-scale yeast ribosome profiling studies) between related protein domains to more directly test if their translation schedule was conserved. Our analysis reveals that the ribosome occupancy profiles of paralogous domains tend to be significantly more similar to one another than to profiles of non-paralogous domains. This trend does not depend on domain length, structural classes, amino acid composition or sequence similarity. Our results indicate that entire ribosome occupancy profiles and not just rare codon locations are conserved between even distantly related domains in yeast, providing support for the hypothesis that translation schedule is conserved between structurally related domains to retain folding pathways and facilitate efficient folding. Availability and implementation Python3 code is available on GitHub at https://github.com/DanNissley/Compare-ribosome-occupancy. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Comparative Genomics of Xanthomonaseuroxanthea and Xanthomonas arboricola pv. juglandis Strains Isolated from a Single Walnut Host Tree

2021 ◽  
Vol 9 (3) ◽  
pp. 624
Author(s):  
Camila Fernandes ◽  
Leonor Martins ◽  
Miguel Teixeira ◽  
Jochen Blom ◽  
Joël F. Pothier ◽  
...  
Keyword(s):  
Extracellular Enzymes ◽  
Walnut Tree ◽  
Size Number ◽  
A Genome ◽  
Type 3 Secretion System ◽  
Xanthomonas Arboricola ◽  
Chromosomal Sequences ◽  
Related Proteins ◽  
Type 3 ◽  
Genome Comparisons

The recent report of distinct Xanthomonas lineages of Xanthomonas arboricola pv. juglandis and Xanthomonas euroxanthea within the same walnut tree revealed that this consortium of walnut-associated Xanthomonas includes both pathogenic and nonpathogenic strains. As the implications of this co-colonization are still poorly understood, in order to unveil niche-specific adaptations, the genomes of three X. euroxanthea strains (CPBF 367, CPBF 424T, and CPBF 426) and of an X. arboricola pv. juglandis strain (CPBF 427) isolated from a single walnut tree in Loures (Portugal) were sequenced with two different technologies, Illumina and Nanopore, to provide consistent single scaffold chromosomal sequences. General genomic features showed that CPBF 427 has a genome similar to other X. arboricola pv. juglandis strains, regarding its size, number, and content of CDSs, while X. euroxanthea strains show a reduction regarding these features comparatively to X. arboricola pv. juglandis strains. Whole genome comparisons revealed remarkable genomic differences between X. arboricola pv. juglandis and X. euroxanthea strains, which translates into different pathogenicity and virulence features, namely regarding type 3 secretion system and its effectors and other secretory systems, chemotaxis-related proteins, and extracellular enzymes. Altogether, the distinct genomic repertoire of X. euroxanthea may be particularly useful to address pathogenicity emergence and evolution in walnut-associated Xanthomonas.

scholarly journals riboCIRC: a comprehensive database of translatable circRNAs

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Huihui Li ◽  
Mingzhe Xie ◽  
Yan Wang ◽  
Ludong Yang ◽  
Zhi Xie ◽  
...  
Keyword(s):  
De Novo ◽  
Species Conservation ◽  
Structure And Function ◽  
Research Community ◽  
Genome Browser ◽  
Valuable Resource ◽  
Sequence Structure ◽  
A Genome ◽  
Context Specific ◽  
And Function

AbstractriboCIRC is a translatome data-oriented circRNA database specifically designed for hosting, exploring, analyzing, and visualizing translatable circRNAs from multi-species. The database provides a comprehensive repository of computationally predicted ribosome-associated circRNAs; a manually curated collection of experimentally verified translated circRNAs; an evaluation of cross-species conservation of translatable circRNAs; a systematic de novo annotation of putative circRNA-encoded peptides, including sequence, structure, and function; and a genome browser to visualize the context-specific occupant footprints of circRNAs. It represents a valuable resource for the circRNA research community and is publicly available at http://www.ribocirc.com.

scholarly journals Evolutionary history and genetic connectivity across highly fragmented populations of an endangered daisy

Heredity ◽  
2021 ◽  
Author(s):  
Yael S. Rodger ◽  
Alexandra Pavlova ◽  
Steve Sinclair ◽  
Melinda Pickup ◽  
Paul Sunnucks
Keyword(s):  
Genetic Diversity ◽  
Gene Flow ◽  
Genetic Differentiation ◽  
Evolutionary History ◽  
Livestock Grazing ◽  
Genetic Connectivity ◽  
Evolutionary Divergence ◽  
Common Component ◽  
A Genome ◽  
Eastern Australia

AbstractConservation management can be aided by knowledge of genetic diversity and evolutionary history, so that ecological and evolutionary processes can be preserved. The Button Wrinklewort daisy (Rutidosis leptorrhynchoides) was a common component of grassy ecosystems in south-eastern Australia. It is now endangered due to extensive habitat loss and the impacts of livestock grazing, and is currently restricted to a few small populations in two regions >500 km apart, one in Victoria, the other in the Australian Capital Territory and nearby New South Wales (ACT/NSW). Using a genome-wide SNP dataset, we assessed patterns of genetic structure and genetic differentiation of 12 natural diploid populations. We estimated intrapopulation genetic diversity to scope sources for genetic management. Bayesian clustering and principal coordinate analyses showed strong population genetic differentiation between the two regions, and substantial substructure within ACT/NSW. A coalescent tree-building approach implemented in SNAPP indicated evolutionary divergence between the two distant regions. Among the populations screened, the last two known remaining Victorian populations had the highest genetic diversity, despite having among the lowest recent census sizes. A maximum likelihood population tree method implemented in TreeMix suggested little or no recent gene flow except potentially between very close neighbours. Populations that were more genetically distinctive had lower genetic diversity, suggesting that drift in isolation is likely driving population differentiation though loss of diversity, hence re-establishing gene flow among them is desirable. These results provide background knowledge for evidence-based conservation and support genetic rescue within and between regions to elevate genetic diversity and alleviate inbreeding.

scholarly journals Conserved Structure and Function in the Granulysin and NK-Lysin Peptide Family

2005 ◽  
Vol 73 (10) ◽  
pp. 6332-6339 ◽  
Author(s):  
Charlotte M. A. Linde ◽  
Susanna Grundström ◽  
Erik Nordling ◽  
Essam Refai ◽  
Patrick J. Brennan ◽  
...  
Keyword(s):  
Mycobacterium Smegmatis ◽  
Three Dimensional ◽  
Antimycobacterial Activity ◽  
Structure And Function ◽  
Loop Structure ◽  
E Coli ◽  
Short Loop ◽  
Peptide Family ◽  
And Function ◽  
Related Proteins

ABSTRACT Granulysin and NK-lysin are homologous bactericidal proteins with a moderate residue identity (35%), both of which have antimycobacterial activity. Short loop peptides derived from the antimycobacterial domains of granulysin, NK-lysin, and a putative chicken NK-lysin were examined and shown to have comparable antimycobacterial but variable Escherichia coli activities. The known structure of the NK-lysin loop peptide was used to predict the structure of the equivalent peptides of granulysin and chicken NK-lysin by homology modeling. The last two adopted a secondary structure almost identical to that of NK-lysin. All three peptides form very similar three-dimensional (3-D) architectures in which the important basic residues assume the same positions in space. The basic residues in granulysin are arginine, while those in NK-lysin and chicken NK-lysin are a mixture of arginine and lysine. We altered the ratio of arginine to lysine in the granulysin fragment to examine the importance of basic residues for antimycobacterial activity. The alteration of the amino acids reduced the activity against E. coli to a larger extent than that against Mycobacterium smegmatis. In granulysin, the arginines in the loop structure are not crucial for antimycobacterial activity but are important for cytotoxicity. We suggest that the antibacterial domains of the related proteins granulysin, NK-lysin, and chicken NK-lysin have conserved their 3-D structure and their function against mycobacteria.

scholarly journals FLAMs: A self-replicating ex vivo model of alveolar macrophages for functional genetic studies

2021 ◽  
Author(s):  
Sean Thomas ◽  
Kathryn Wierenga ◽  
James Pestka ◽  
Andrew Olive
Keyword(s):  
Alveolar Macrophages ◽  
Ex Vivo ◽  
Fetal Liver ◽  
Expression Profiles ◽  
Surface Expression ◽  
Specific Gene ◽  
Ex Vivo Model ◽  
A Genome ◽  
Underlying Mechanisms ◽  
And Function

Alveolar macrophages (AMs) are tissue resident cells in the lungs derived from the fetal liver that maintain lung homeostasis and respond to inhaled stimuli. While the importance of AMs is undisputed, they remain refractory to standard experimental approaches and high-throughput functional genetics as they are challenging to isolate and rapidly lose AM properties in standard culture. This limitation hinders our understanding of key regulatory mechanisms that control AM maintenance and function. Here, we describe the development of a new model, fetal liver-derived alveolar-like macrophages (FLAMs), which maintains cellular morphologies, expression profiles, and functional mechanisms similar to murine AMs. FLAMs combine treatment with two key cytokines for AM maintenance, GM-CSF and TGFβ. We leveraged the long-term stability of FLAMs to develop functional genetic tools using CRISPR-Cas9-mediated gene editing. Targeted editing confirmed the role of AM-specific gene Marco and the IL-1 receptor Il1r1 in modulating the AM response to crystalline silica. Furthermore, a genome-wide knockout library using FLAMs identified novel genes required for surface expression of the AM marker Siglec-F, most notably those related to the peroxisome. Taken together, our results suggest that FLAMs are a stable, self-replicating model of AM function that enables previously impossible global genetic approaches to define the underlying mechanisms of AM maintenance and function.

scholarly journals An ancestral recombination graph of human, Neanderthal, and Denisovan genomes

2021 ◽  
Vol 7 (29) ◽  
pp. eabc0776
Author(s):  
Nathan K. Schaefer ◽  
Beth Shapiro ◽  
Richard E. Green
Keyword(s):  
Incomplete Lineage Sorting ◽  
Simulated Data ◽  
Modern Human ◽  
Ancestral Recombination Graph ◽  
Lineage Sorting ◽  
Human Genomes ◽  
Genome Wide ◽  
A Genome ◽  
Graph Inference ◽  
And Function

Many humans carry genes from Neanderthals, a legacy of past admixture. Existing methods detect this archaic hominin ancestry within human genomes using patterns of linkage disequilibrium or direct comparison to Neanderthal genomes. Each of these methods is limited in sensitivity and scalability. We describe a new ancestral recombination graph inference algorithm that scales to large genome-wide datasets and demonstrate its accuracy on real and simulated data. We then generate a genome-wide ancestral recombination graph including human and archaic hominin genomes. From this, we generate a map within human genomes of archaic ancestry and of genomic regions not shared with archaic hominins either by admixture or incomplete lineage sorting. We find that only 1.5 to 7% of the modern human genome is uniquely human. We also find evidence of multiple bursts of adaptive changes specific to modern humans within the past 600,000 years involving genes related to brain development and function.

Timing during translation matters: synonymous mutations in human pathologies influence protein folding and function

2018 ◽  
Vol 46 (4) ◽  
pp. 937-944 ◽  
Author(s):  
Robert Rauscher ◽  
Zoya Ignatova
Keyword(s):  
Protein Folding ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Synonymous Mutations ◽  
Translation Velocity ◽  
Disease Penetrance ◽  
And Function ◽  
Related Proteins ◽  
Translational Speed ◽  
Fine Tune

Ribosomes translate mRNAs with non-uniform speed. Translation velocity patterns are a conserved feature of mRNA and have evolved to fine-tune protein folding, expression and function. Synonymous single-nucleotide polymorphisms (sSNPs) that alter programmed translational speed affect expression and function of the encoded protein. Synergistic advances in next-generation sequencing have led to the identification of sSNPs associated with disease penetrance. Here, we draw on studies with disease-related proteins to enhance our understanding of mechanistic contributions of sSNPs to functional alterations of the encoded protein. We emphasize the importance of identification of sSNPs along with disease-causing mutations to understand genotype–phenotype relationships.

Analysis of MicroRNA Transcriptomes Insights into the miR-148a-3p Inducer of Rumen Development in Goats

2020 ◽  
Author(s):  
Tao Zhong ◽  
Cheng Wang ◽  
Jiangtao Hu ◽  
Xiaoyong Chen ◽  
Lili Niu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Genetic Regulation ◽  
Mapk Signaling ◽  
Regulation Mechanism ◽  
Ras Signaling ◽  
Genome Wide ◽  
A Genome ◽  
Differentially Expressed Mirnas ◽  
And Function

Abstract Background: Rumen is an important digestive organ of ruminant. From fetal to adult stage, the morphology, structure and function of rumen have changed significantly. But the intrinsic genetic regulation is still limited. We previously reported a genome-wide expression profile of miRNAs in prenatal goat rumens. In the present study, we rejoined analyzed the transcriptomes of rumen miRNAs during prenatal (E60 and E135) and postnatal (D30 and D150) stages.Results: A total of 66 differentially expressed miRNAs (DEMs) were identified in the rumen tissues from D30 and D150 goats. Of these, 17 DEMs were consistently highly expressed in the rumens at the preweaning stages (E60, E135 and D30), while down-regulated at D150. Noteworthy, annotation analysis revealed that the target genes regulated by the DEMs were mainly enriched in MAPK signaling pathway, Jak-STAT signaling pathway and Ras signaling pathway. Interestingly, the expression of miR-148a-3p was significantly high in the embryonic stage and down-regulated at D150. The potential binding sites between miR-148a-3p and QKI were predicted by the TargetScan and verified by the dual luciferase report assay. The co-localization of miR-148a-3p and QKI was observed not in intestinal tracts but in rumen tissues by in situ hybridization. Moreover, the expression of miR-148a-3p in the epithelium was significantly higher than that in the other layers, suggesting that miR-148a-3p involve in the development of rumen epithelial cells by targeting QKI. Subsequently, miR-148a-3p inhibitor was found to induce the proliferation of GES-1 cells.Conclusions: Taken together, these results identified the DEMs involved in the development of rumen and provided an insight into the regulation mechanism of goat rumens during development.

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