scholarly journals Evolutionary Analyses of RNA Editing and Amino Acid Recoding in Cephalopods

2019 ◽  
Author(s):  
Mingye (Christina) Wang ◽  
Erik Mohlhenrich
Keyword(s):  
Amino Acid ◽  
Candidate Genes ◽  
Rna Editing ◽  
Amino Acid Level ◽  
Nucleotide Composition ◽  
Model Organisms ◽  
Future Research ◽  
Amino Acid Substitutions ◽  
Behavioral Complexity ◽  
Fitness Advantage

AbstractRNA editing is a post-transcriptional modification process that alters nucleotides of mRNA and consequently the amino acids of the translated protein without changing the original DNA sequence. In human and other mammals, amino acid recoding from RNA editing is rare, and most edits are non-adaptive and provide no fitness advantage (1). However, recently it was discovered that in soft-bodied cephalopods, which are exceptionally intelligent and include squid, octopus, and cuttlefish, RNA editing is widespread and positively selected (2). To examine the effects of RNA editing on individual genes, we developed a “diversity score” system that quantitatively assesses the amount of diversity generated in each gene, incorporating combinatorial diversity and the radicalness of amino acid changes. Using this metric, we compiled a list of top 100 genes across the cephalopod species that are most diversified by RNA editing. This list of candidate genes provides directions for future research into the specific functional impact of RNA editing in terms of protein structure and cellular function on individual proteins. Additionally, considering the connection of RNA editing to the nervous system, and the exceptional intelligence of cephalopod, the candidate genes may shed light to the molecular development of behavioral complexity and intelligence. To further investigate global influences of RNA editing on the transcriptome, we investigated changes in nucleotide composition and codon usage biases in edited genes and coleoid transcriptome in general. Results show that these features indeed correlate with editing and may correspond to causes or effects of RNA editing. In addition, we characterized the unusual RNA editing in cephalopods by analyzing ratio of radical to conservative amino acid substitutions (R/C) and distribution of amino acid recoding from editing. Our results show that compared to model organisms, editing in cephalopods have significantly decreased R/C ratio and distinct distribution of amino acid substitutions that favor conservative over radical changes, indicating selection at the amino acid level and providing a potential mechanism for the evolution of widespread RNA editing in cephalopods.

Viral fitness and antigenic determinants of porcine parvovirus at the amino acid level of the capsid protein

2021 ◽  
Author(s):  
André Felipe Streck ◽  
Cláudio Wageck Canal ◽  
Uwe Truyen
Keyword(s):  
Amino Acid ◽  
Capsid Protein ◽  
Immune Escape ◽  
Amino Acid Level ◽  
Binding Activity ◽  
Viral Fitness ◽  
Antigenic Determinants ◽  
Amino Acid Substitutions ◽  
Porcine Parvovirus ◽  
Predominant Factor

Since 2001, strains of porcine parvovirus (PPV), designated 27a -like strains, were observed in Europe, suggesting a predominance of these viruses over older strains. The reasons for the obvious evolutionary advantage are unknown. Here, a series of mutants containing amino acid replacements found in the predominant field strains were generated in a PPV-NADL2 background and their impact on replication efficiency and antibody binding activity was determined. Some amino acid substitutions observed in the 27a- like strains significantly increased viral fitness and decreased neutralization activity of sera raised against commercial vaccines and old virus strains (e.g. NADL2). These mutant viruses and a monoclonal antibody raised against a classical PPV strain defined an 27a-specific neutralizing epitope around amino acid 228 of the capsid protein VP2. Based on the analysis of the mutant viruses, it is hypothesized that the predominant factor for the global spread of the PPV-27a strain substitutions is an increased viral fitness of the 27a- like viruses, possibly supported by a partial immune selection. This is reminiscent to the evolution of canine parvovirus and worldwide replacement of the original virus by the so-called new antigenic types. Importance Porcine parvovirus is one of the most important causes of reproductive failure in swine. Recently, despite the continuous use of vaccines, “new” strains emerged, leading to the hypothesis that the emergence of new amino acid substitutions could be a viral adaptation to the immune response against the commercial vaccines. Our results indicate the amino acid substitutions observed in the 27a -like strains can modify viral fitness and antigenicity. However, an absolute immune escape was not evident.

scholarly journals CRISPR-RT: A web service for designing CRISPR-C2c2 crRNA with improved target specificity

2017 ◽  
Author(s):  
Houxiang Zhu ◽  
Emily Richmond ◽  
Chun Liang
Keyword(s):  
Web Service ◽  
Genome Editing ◽  
Rna Editing ◽  
Model Organisms ◽  
Future Research ◽  
Target Specificity ◽  
Link Type ◽  
Wide Range ◽  
Set Up

AbstractCRISPR-Cas systems have been successfully applied in genome editing. Recently, the CRISPR-C2c2 system has been reported as a tool for RNA editing. Here we describe CRISPR-RT (CRISPR RNA-Targeting), the first web service to help biologists design the crRNA with improved target specificity for the CRISPR-C2c2 system. CRISPR-RT allows users to set up a wide range of parameters, making it highly flexible for current and future research in CRISPR-based RNA editing. CRISPR-RT covers major model organisms and can be easily extended to cover other species. CRISPR-RT will empower researchers in RNA editing. It is available at http://bioinfolab.miamioh.edu/CRISPR-RT.

scholarly journals Nucleotide Polymorphism and Natural Selection at the Pantophysin (Pan I) Locus in the Atlantic Cod, Gadus morhua (L.)

Genetics ◽  
2001 ◽  
Vol 157 (1) ◽  
pp. 317-330 ◽  
Author(s):  
Grant H Pogson
Keyword(s):  
Natural Selection ◽  
Amino Acid ◽  
Gadus Morhua ◽  
Atlantic Cod ◽  
Amino Acid Level ◽  
Amino Acid Substitutions ◽  
Significant Heterogeneity ◽  
Nucleotide Sequence Variation ◽  
Spatially Varying ◽  
Spatially Varying Selection

Abstract Molecular studies of nucleotide sequence variation have rarely attempted to test hypotheses related to geographically varying patterns of natural selection. The present study tested the role of spatially varying selection in producing significant linkage disequilibrium and large differences in the frequencies of two common alleles at the pantophysin (Pan I) locus among five populations of the Atlantic cod, Gadus morhua. Nucleotide sequences of 124 Pan I alleles showed strong evidence for an unusual mix of balancing and directional selection but no evidence of stable geographically varying selection. The alleles were highly divergent at both the nucleotide level (differing on average by 19 mutations) and at amino acid level (each having experienced three amino acid substitutions since diverging from a common ancestral allele). All six amino acid substitutions occurred in a 56-residue intravesicular loop (IV1 domain) of the vesicle protein and each involved a radical change. An analysis of molecular variation revealed significant heterogeneity in the frequencies of recently derived mutations segregating within both allelic classes, suggesting that two selective sweeps may be presently occurring among populations. The dynamic nature of the Pan I polymorphism in G. morhua and clear departure from equilibrium conditions invalidate a simple model of spatially varying selection.

scholarly journals Coding palindromes in mitochondrial genes of Nematomorpha

2019 ◽  
Vol 47 (13) ◽  
pp. 6858-6870 ◽  
Author(s):  
Kirill V Mikhailov ◽  
Boris D Efeykin ◽  
Alexander Y Panchin ◽  
Dmitry A Knorre ◽  
Maria D Logacheva ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Function ◽  
Inverted Repeat ◽  
Amino Acid Level ◽  
Nucleotide Composition ◽  
Mitochondrial Genomes ◽  
Inverted Repeats ◽  
Protein Coding ◽  
Dna Elements ◽  
And Function

Abstract Inverted repeats are common DNA elements, but they rarely overlap with protein-coding sequences due to the ensuing conflict with the structure and function of the encoded protein. We discovered numerous perfect inverted repeats of considerable length (up to 284 bp) embedded within the protein-coding genes in mitochondrial genomes of four Nematomorpha species. Strikingly, both arms of the inverted repeats encode conserved regions of the amino acid sequence. We confirmed enzymatic activity of the respiratory complex I encoded by inverted repeat-containing genes. The nucleotide composition of inverted repeats suggests strong selection at the amino acid level in these regions. We conclude that the inverted repeat-containing genes are transcribed and translated into functional proteins. The survey of available mitochondrial genomes reveals that several other organisms possess similar albeit shorter embedded repeats. Mitochondrial genomes of Nematomorpha demonstrate an extraordinary evolutionary compromise where protein function and stringent secondary structure elements within the coding regions are preserved simultaneously.

scholarly journals Identification of Genetic Alterations Associated with Acquired Colistin Resistance in Klebsiella pneumoniae Isogenic Strains by Whole-Genome Sequencing

Antibiotics ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 374
Author(s):  
Myeongjin Choi ◽  
Kwan Soo Ko
Keyword(s):  
Amino Acid ◽  
Klebsiella Pneumoniae ◽  
Whole Genome Sequencing ◽  
Candidate Genes ◽  
Genome Sequencing ◽  
Parental Strain ◽  
Genetic Alterations ◽  
Amino Acid Substitutions ◽  
Whole Genome ◽  
Colistin Resistance

The present study was undertaken to find novel genes associated with colistin resistance in Klebsiella pneumoniae. Five colistin-resistant mutants were derived from four colistin-susceptible parental K. pneumoniae strains belonging to different clones. Whole-genome sequencing was performed for the nine K. pneumoniae strains to screen altered candidate genes. Expression levels of genes with amino acid alterations in derivative strains were determined using quantitative real-time Polymerase chain reaction (PCR). Colistin susceptibility was examined in a parental strain complemented with altered candidate genes. Overall, 13 genetic alterations were identified in five pairs of isogenic K. pneumoniae strains. Genetic alterations related to KP1_3468, including the insertion of an IS5-like element in an intergenic or coding region and amino acid substitutions, were identified in three separate derivative strains. Amino acid substitutions and deletion of PhoQ were determined in one derivative strain. With inactivation of CrrA and substituted CrrB, amino acid substitutions and deletion were identified in a repressor of galETK operon (KP1_0061) and hypothetical protein (KP1_3620), respectively. Decreased colistin susceptibility was observed in a parental strain complemented with KP1-0061, but not a KP1-3620 gene. This study demonstrated diverse genetic paths to colistin resistance in K. pneumoniae. Our results suggest that a repressor of galETK operon may play an important role in colistin resistance in K. pneumoniae.

scholarly journals Possible changes in fidelity of DNA polymerase δ in ancestral mammals

2020 ◽  
Author(s):  
Kazutaka Katoh ◽  
Naoyuki Iwabe ◽  
Takashi Miyata
Keyword(s):  
Amino Acid ◽  
Dna Polymerase ◽  
Phylogenetic Analyses ◽  
Amino Acid Level ◽  
Amino Acid Substitutions ◽  
Dna Polymerase Δ ◽  
Time Period ◽  
Mammalian Lineage ◽  
Exonuclease Domain

AbstractDNA polymerase δ (polδ) is one of the major DNA polymerases that replicate chromosomal genomes in eukaryotes. Given the essential role of this protein, its phylogenetic tree was expected to reflect the relationship between taxa, like many other essential proteins. However, the tree of the catalytic subunit of polδ showed an unexpectedly strong heterogeneity among vertebrate lineages in evolutionary rate at the amino acid level, suggesting unusual amino acid substitutions specifically in the ancestral mammalian lineage. Structural and phylogenetic analyses were used to pinpoint where and when these amino acid substitutions occurred: around the 3′-5′ exonuclease domain in later mammal ancestry, after the split between monotremes and therians. The 3′-5′ exonuclease domain of this protein is known to have an impact on the fidelity of replication. Based on these observations, we explored the possibility that the amino acid substitutions we identified in polδ affected the mutation rate of entire chromosomal genomes in this time period.

scholarly journals DescribePROT: database of amino acid-level protein structure and function predictions

2020 ◽  
Vol 49 (D1) ◽  
pp. D298-D308 ◽  
Author(s):  
Bi Zhao ◽  
Akila Katuwawala ◽  
Christopher J Oldfield ◽  
A Keith Dunker ◽  
Eshel Faraggi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Function ◽  
Acid Level ◽  
Solvent Accessibility ◽  
Amino Acid Level ◽  
Structure And Function ◽  
Model Organisms ◽  
Comprehensive Collection ◽  
Uniprot Accession ◽  
And Function

Abstract We present DescribePROT, the database of predicted amino acid-level descriptors of structure and function of proteins. DescribePROT delivers a comprehensive collection of 13 complementary descriptors predicted using 10 popular and accurate algorithms for 83 complete proteomes that cover key model organisms. The current version includes 7.8 billion predictions for close to 600 million amino acids in 1.4 million proteins. The descriptors encompass sequence conservation, position specific scoring matrix, secondary structure, solvent accessibility, intrinsic disorder, disordered linkers, signal peptides, MoRFs and interactions with proteins, DNA and RNAs. Users can search DescribePROT by the amino acid sequence and the UniProt accession number and entry name. The pre-computed results are made available instantaneously. The predictions can be accesses via an interactive graphical interface that allows simultaneous analysis of multiple descriptors and can be also downloaded in structured formats at the protein, proteome and whole database scale. The putative annotations included by DescriPROT are useful for a broad range of studies, including: investigations of protein function, applied projects focusing on therapeutics and diseases, and in the development of predictors for other protein sequence descriptors. Future releases will expand the coverage of DescribePROT. DescribePROT can be accessed at http://biomine.cs.vcu.edu/servers/DESCRIBEPROT/.

scholarly journals Do aye-ayes echolocate? Studying convergent genomic evolution in a primate auditory specialist

2016 ◽  
Author(s):  
Richard J. Bankoff ◽  
Michael Jerjos ◽  
Baily Hohman ◽  
M Elise Lauterbur ◽  
Logan Kistler ◽  
...  
Keyword(s):  
Amino Acid ◽  
Behavioral Ecology ◽  
Auditory Processing ◽  
De Novo ◽  
Amino Acid Level ◽  
Processing System ◽  
Model Organisms ◽  
Sequencing Data ◽  
Coding Region ◽  
Insect Larvae

AbstractSeveral taxonomically distinct mammalian groups – certain microbats and cetaceans (e.g. dolphins) – share both morphological adaptations related to echolocation behavior and strong signatures of convergent evolution at the amino acid level across seven genes related to auditory processing. Aye-ayes (Daubentonia madagascariensis) are nocturnal lemurs with a derived auditory processing system. Aye-ayes tap rapidly along the surfaces of dead trees, listening to reverberations to identify the mines of wood-boring insect larvae; this behavior has been hypothesized to functionally mimic echolocation. Here we investigated whether there are signals of genomic convergence between aye-ayes and known mammalian echolocators. We developed a computational pipeline (BEAT: Basic Exon Assembly Tool) that produces consensus sequences for regions of interest from shotgun genomic sequencing data for non-model organisms without requiring de novo genome assembly. We reconstructed complete coding region sequences for the seven convergent echolocating bat-dolphin genes for aye-ayes and another lemur. Sequences were compared in a phylogenetic framework to those of bat and dolphin echolocators and appropriate non-echolocating outgroups. Our analysis reaffirms the existence of amino acid convergence at these loci among echolocating bats and dolphins; we also detected unexpected signals of convergence between echolocating bats and both mice and elephants. However, we observed no significant signal of amino acid convergence between aye-ayes and echolocating bats and dolphins; our results thus suggest that aye-aye tap-foraging auditory adaptations represent distinct evolutionary innovations. These results are also consistent with a developing consensus that convergent behavioral ecology is not necessarily a reliable guide to convergent molecular evolution.

scholarly journals ADAR-Independent A-to-I RNA Editing is Generally Adaptive for Sexual Reproduction in Fungi

2016 ◽  
Author(s):  
Qinhu Wang ◽  
Cong Jiang ◽  
Huiquan Liu ◽  
Jin-Rong Xu
Keyword(s):  
Amino Acid ◽  
Sexual Reproduction ◽  
Rna Editing ◽  
Protein Structures ◽  
Biological Significance ◽  
Chemical Properties ◽  
Rna Modification ◽  
Amino Acid Substitutions ◽  
Protein Functions ◽  
Conserved Genes

ABSTRACTADAR-mediated A-to-I RNA editing is a well-known RNA modification mechanism in metazoans that can cause nonsynonymous changes leading to amino acid substitutions. Despite a few cases that are clearly functionally important, the biological significance of most nonsynonymous editing sites in animals remains largely unknown. Recently, genome-wide A-to-I editing was found to occur mainly in the coding regions and specifically during sexual reproduction in the wheat scab fungus Fusarium graminearum that lacks ADAR orthologs. In this study, we found that both the frequency and editing level of nonsynonymous editing is significantly higher than those of synonymous editing, suggesting that nonsynonymous editing is generally beneficial and under positive selection in F. graminearum. We also showed that nonsynonymous editing favorably targets functionally more important and more conserved genes, but at less-conserved sites, indicating that the RNA editing system is adapted to fine turn protein functions by avoiding potentially deleterious editing events. Furthermore, nonsynonymous editing in F. graminearum was found to be under codon-specific selection and most types of codon changes tend to cause amino acid substitutions with distinct physical-chemical properties and smaller molecular weights, which likely have more profound impact on protein structures and functions. In addition, we found that the most abundant synonymous editing of leucine codons is adapted to fine turn the protein expression by increasing codon usage bias. These results clearly show that A-to-I RNA editing in fungi is generally adaptive and recoding RNA editing may play an important role in sexual development in filamentous ascomycetes.

Recombinant Variants of Tissue-Type Plasminogen Activator Containing Amino Acid Substitutions in the Finger Domain

1992 ◽  
Vol 68 (06) ◽  
pp. 672-677 ◽  
Author(s):  
Hitoshi Yahara ◽  
Keiji Matsumoto ◽  
Hiroyuki Maruyama ◽  
Tetsuya Nagaoka ◽  
Yasuhiro Ikenaka ◽  
...  
Keyword(s):  
Amino Acid ◽  
Plasminogen Activator ◽  
Half Life ◽  
Tissue Type ◽  
Clot Lysis ◽  
Amino Acid Substitutions ◽  
Wild Type ◽  
Plasma Clot ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator

SummaryTissue-type plasminogen activator (t-PA) is a fibrin-specific agent which has been used to treat acute myocardial infarction. In an attempt to clarify the determinants for its rapid clearance in vivo and high affinity for fibrin clots, we produced five variants containing amino acid substitutions in the finger domain, at amino acid residues 7–9, 10–14, 15–19, 28–33, and 37–42. All the variants had a prolonged half-life and a decreased affinity for fibrin of various degrees. The 37–42 variant demonstrated about a 6-fold longer half-life with a lower affinity for fibrin. Human plasma clot lysis assay estimated the fibrinolytic activity of the 37–42 variant to be 1.4-fold less effective than that of the wild-type rt-PA. In a rabbit jugular vein clot lysis model, doses of 1.0 and 0.15 mg/kg were required for about 70% lysis in the wild-type and 37–42 variant, respectively. Fibrinogen was degraded only when the wild-type rt-PA was administered at a dose of 1.0 mg/kg. These findings suggest that the 37–42 variant can be employed at a lower dosage and that it is a more fibrin-specific thrombolytic agent than the wild-type rt-PA.

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