Insertions and deletions trigger adaptive walks in
            Drosophila
            proteins

Maps that relate all possible genotypes or phenotypes to fitness—fitness landscapes—are central to the evolution of life, but remain poorly known. An insertion or a deletion (indel) of one or several amino acids constitutes a substantial leap of a protein within the space of amino acid sequences, and it is unlikely that after such a leap the new sequence corresponds precisely to a fitness peak. Thus, one can expect an indel in the protein-coding sequence that gets fixed in a population to be followed by some number of adaptive amino acid substitutions, which move the new sequence towards a nearby fitness peak. Here, we study substitutions that occur after a frame-preserving indel in evolving proteins of Drosophila . An insertion triggers 1.03 ± 0.75 amino acid substitutions within the protein region centred at the site of insertion, and a deletion triggers 4.77 ± 1.03 substitutions within such a region. The difference between these values is probably owing to a higher fraction of effectively neutral insertions. Almost all of the triggered amino acid substitutions can be attributed to positive selection, and most of them occur relatively soon after the triggering indel and take place upstream of its site. A high fraction of substitutions that follow an indel occur at previously conserved sites, suggesting that an indel substantially changes selection that shapes the protein region around it. Thus, an indel is often followed by an adaptive walk of length that is in agreement with the theory of molecular adaptation.

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Comprehensive mutagenesis to identify amino acid residues contributing to the difference in thermostability between two originally thermostable ancestral proteins

PLoS ONE ◽

10.1371/journal.pone.0258821 ◽

2021 ◽

Vol 16 (10) ◽

pp. e0258821

Author(s):

Satoshi Akanuma ◽

Minako Yamaguchi ◽

Akihiko Yamagishi

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Rational Design ◽

Synergistic Effects ◽

Amino Acid Sequences ◽

Amino Acid Substitutions ◽

Amino Acid Residues ◽

Identify Amino Acid ◽

The Difference ◽

The Stability

Further improvement of the thermostability of inherently thermostable proteins is an attractive challenge because more thermostable proteins are industrially more useful and serve as better scaffolds for protein engineering. To establish guidelines that can be applied for the rational design of hyperthermostable proteins, we compared the amino acid sequences of two ancestral nucleoside diphosphate kinases, Arc1 and Bac1, reconstructed in our previous study. Although Bac1 is a thermostable protein whose unfolding temperature is around 100°C, Arc1 is much more thermostable with an unfolding temperature of 114°C. However, only 12 out of 139 amino acids are different between the two sequences. In this study, one or a combination of amino acid(s) in Bac1 was/were substituted by a residue(s) found in Arc1 at the same position(s). The best mutant, which contained three amino acid substitutions (S108D, G116A and L120P substitutions), showed an unfolding temperature more than 10°C higher than that of Bac1. Furthermore, a combination of the other nine amino acid substitutions also led to improved thermostability of Bac1, although the effects of individual substitutions were small. Therefore, not only the sum of the contributions of individual amino acids, but also the synergistic effects of multiple amino acids are deeply involved in the stability of a hyperthermostable protein. Such insights will be helpful for future rational design of hyperthermostable proteins.

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Evolution and Adaptation of the Avian H7N9 Virus into the Human Host

Microorganisms ◽

10.3390/microorganisms8050778 ◽

2020 ◽

Vol 8 (5) ◽

pp. 778

Author(s):

Andrew T. Bisset ◽

Gerard F. Hoyne

Keyword(s):

Amino Acid ◽

Avian Influenza ◽

Influenza A ◽

Amino Acid Sequences ◽

Influenza Viruses ◽

Amino Acid Substitutions ◽

Upper Respiratory Tract ◽

Viral Polymerase ◽

Evolutionary Changes ◽

Avian Origin

Influenza viruses arise from animal reservoirs, and have the potential to cause pandemics. In 2013, low pathogenic novel avian influenza A(H7N9) viruses emerged in China, resulting from the reassortment of avian-origin viruses. Following evolutionary changes, highly pathogenic strains of avian influenza A(H7N9) viruses emerged in late 2016. Changes in pathogenicity and virulence of H7N9 viruses have been linked to potential mutations in the viral glycoproteins hemagglutinin (HA) and neuraminidase (NA), as well as the viral polymerase basic protein 2 (PB2). Recognizing that effective viral transmission of the influenza A virus (IAV) between humans requires efficient attachment to the upper respiratory tract and replication through the viral polymerase complex, experimental evidence demonstrates the potential H7N9 has for increased binding affinity and replication, following specific amino acid substitutions in HA and PB2. Additionally, the deletion of extended amino acid sequences in the NA stalk length was shown to produce a significant increase in pathogenicity in mice. Research shows that significant changes in transmissibility, pathogenicity and virulence are possible after one or a few amino acid substitutions. This review aims to summarise key findings from that research. To date, all strains of H7N9 viruses remain restricted to avian reservoirs, with no evidence of sustained human-to-human transmission, although mutations in specific viral proteins reveal the efficacy with which these viruses could evolve into a highly virulent and infectious, human-to-human transmitted virus.

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Non-Penicillin-Susceptible Streptococcus suis Isolated from Humans

Pathogens ◽

10.3390/pathogens10091178 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1178

Author(s):

Nichari Bamphensin ◽

Peechanika Chopjitt ◽

Rujirat Hatrongjit ◽

Parichart Boueroy ◽

Nahuel Fittipaldi ◽

...

Keyword(s):

Amino Acid ◽

Antimicrobial Resistance ◽

Resistance Genes ◽

Streptococcus Suis ◽

Amino Acid Substitutions ◽

Continuous Control ◽

Antimicrobial Resistance Genes ◽

Genes Encoding ◽

Invasive Infections ◽

Almost All

Streptococcus suis is a pathogen that causes invasive infections in humans and pigs. In this study, 448 S. suis isolates recovered from human infections in Thailand were characterized with regard to their antimicrobial susceptibility and antimicrobial resistance genes, including, for non-penicillin-susceptible isolates, sequence analyses of five genes encoding penicillin-binding proteins (pbp1a, pbp1b, pbp2a, pbp2b, and pbp2x). All 448 isolates were susceptible to cefepime and ceftriaxone, whereas 99.6%, 91.7%, and 72.9% of the isolates were susceptible to levofloxacin, penicillin, and chloramphenicol, respectively. Almost all isolates were resistant to tetracycline (98.2%), clindamycin (94%), erythromycin (92.4%), and azithromycin (82.6%). Genes tet(O) and ermB were the predominant resistance genes detected among macrolide- and tetracycline-resistant isolates. A total of 37 out of 448 isolates (8.2%) showed intermediately resistance to penicillin. Most of these isolates (59.5%) belonged to serotype 2-ST233. Comparison of the predicted translated sequences of five PBP proteins of a penicillin-susceptible isolate (strain P1/7) to the respective PBP sequences of ten non-penicillin-susceptible isolates revealed multiple amino acid substitutions. Isolates of CC221/234 showed highly variable amino acid substitutions in all PBP proteins. An ST104 isolate had a higher number of amino acid substitutions in PBP2X. Isolates belonging to CC233/379 had numerous substitutions in PBP2B and PBP2X. ST25 isolates exhibited fewer amino acid substitutions than isolates of other STs in all five PBPs. The antimicrobial resistance of S. suis is increasing worldwide; therefore, restrictions on antimicrobial use, continuous control, and the surveillance of this bacterium throughout the pork supply chain are crucial for ensuring public health and must be a priority concern.

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Single Passage of Human Metapneumovirus in LLC-MK2 Cells Does Not Affect Viral Protein-Coding Capacity

Genome Announcements ◽

10.1128/genomea.00440-18 ◽

2018 ◽

Vol 6 (21) ◽

Author(s):

Simon Loevenich ◽

Aleksandr Ianevski ◽

Eneli Oitmaa ◽

Denis E. Kainov ◽

Marit W. Anthonsen

Keyword(s):

Amino Acid ◽

Viral Protein ◽

Complete Genome ◽

Human Metapneumovirus ◽

Amino Acid Sequences ◽

Paired Comparisons ◽

Genome Sequences ◽

Protein Coding ◽

Single Passage ◽

Coding Capacity

ABSTRACT Here, we report the complete genome sequences of human metapneumovirus (HMPV) prior to and after passaging in LLC-MK2 cells. Paired comparisons of the 13,335-nucleotide genomes revealed that the virus acquired the T10736C transition in its genome, which did not affect the amino acid sequences of HMPV proteins.

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The cDNA and protein sequences of human lactate dehydrogenase B

Biochemical Journal ◽

10.1042/bj2480933 ◽

1987 ◽

Vol 248 (3) ◽

pp. 933-936 ◽

Cited By ~ 31

Author(s):

I Sakai ◽

F S Sharief ◽

Y C Pan ◽

S S Li

Keyword(s):

Amino Acid ◽

Lactate Dehydrogenase ◽

Amino Acid Composition ◽

Acid Composition ◽

Amino Acid Sequences ◽

British Library ◽

Amino Acid Residues ◽

Coding Region ◽

Cdna Insert ◽

Protein Coding

Human lactate dehydrogenase B (LDH-B) cDNA was isolated and sequenced. The LDH-B cDNA insert consists of the protein-coding sequence (999 bp), the 5′ (54 bp) and 3′ (203 bp) non-coding regions, and the poly(A) tail (50 bp). The predicted sequence of 333 amino acid residues was confirmed by amino acid composition and/or sequence analyses of a total of 185 (56%) residues from tryptic peptides of human LDH-B protein. The nucleotide and amino acid sequences of the human LDH-B coding region show 68% and 75% homologies respectively with those of the human LDH-A. The peptide map and amino acid composition data have been deposited as Supplementary Publication SUP 50139 (7 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies are available on prepayment [see Biochem. J. (1987) 241, 5].

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Supervised learning of protein thermal stability using sequence mining and distribution statistics of network centrality

10.1101/777177 ◽

2019 ◽

Author(s):

Ankit Sharma ◽

Ganesh Bagler ◽

Debajyoti Bera

Keyword(s):

Thermal Stability ◽

Amino Acid ◽

Amino Acid Sequences ◽

Molecular Structures ◽

Network Centrality ◽

Learning Approaches ◽

Peptide Bonds ◽

The Difference ◽

Structural Networks ◽

Feature Selection Techniques

AbstractMotivationIt is expected that the difference in the thermal stability of mesophilic and thermophilic proteins arises, in part at least, from the differences in their molecular structures and amino acid compositions. Existing machine learning approaches for supervised classification of proteins rely on the features derived from the structural networks and the amino acid sequences. However, the network features used leave out several important network centrality values, the statistic used is a simple average and the sequence features used are hand-picked leading to an accuracy of 90%.ResultsWe show that discriminating sub-sequences of the amino acid sequences can significantly improve classification accuracy compared to the existing approaches of counting amino acids, di-peptide or even tri-peptide bonds. We identify notions of network centrality, specifically that depends on the distances between Cα atoms, that appears to correlate better with thermal stability compared to the existing network features. We also show how to generate better statistics from the node- and edge-wise centrality values that more accurately captures the variations in their values for different types of proteins. These improved feature selection techniques make it possible to classify between thermophilic and mesophilic proteins with 96% accuracy and 99% area under ROC.AvailabilityThe dataset and source code used are available at https://github.com/ankits0207/[email protected].

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Mitochondrial genomes of twelve species of hyperdiverse Trigonopterus weevils

PeerJ ◽

10.7717/peerj.10017 ◽

2020 ◽

Vol 8 ◽

pp. e10017

Author(s):

Raden Pramesa Narakusumo ◽

Alexander Riedel ◽

Joan Pons

Keyword(s):

Amino Acid ◽

Phylogenetic Signal ◽

Mitochondrial Protein ◽

Amino Acid Sequences ◽

Mitochondrial Genomes ◽

Length Variation ◽

Codon Site ◽

Protein Coding ◽

Large Variability ◽

Molecular Features

Mitochondrial genomes of twelve species of Trigonopterus weevils are presented, ten of them complete. We describe their gene order and molecular features and test their potential for reconstructing the phylogeny of this hyperdiverse genus comprising > 1,000 species. The complete mitochondrial genomes examined herein ranged from 16,501 bp to 21,007 bp in length, with an average AT content of 64.2% to 69.7%. Composition frequencies and skews were generally lower across species for atp6, cox1-3, and cob genes, while atp8 and genes coded on the minus strand showed much higher divergence at both nucleotide and amino acid levels. Most variation within genes was found at the codon level with high variation at third codon sites across species, and with lesser degree at the coding strand level. Two large non-coding regions were found, CR1 (between rrnS and trnI genes) and CR2 (between trnI and trnQ), but both with large variability in length; this peculiar structure of the non-coding region may be a derived character of Curculionoidea. The nad1 and cob genes exhibited an unusually high interspecific length variation of up to 24 bp near the 3′ end. This pattern was probably caused by a single evolutionary event since both genes are only separated by trnS2 and length variation is extremely rare in mitochondrial protein coding genes. We inferred phylogenetic trees using protein coding gene sequences implementing both maximum likelihood and Bayesian approaches, each for both nucleotide and amino acid sequences. While some clades could be retrieved from all reconstructions with high confidence, there were also a number of differences and relatively low support for some basal nodes. The best partition scheme of the 13 protein coding sequences obtained by IQTREE suggested that phylogenetic signal is more accurate by splitting sequence variation at the codon site level as well as coding strand, rather than at the gene level. This result corroborated the different patterns found in Trigonopterus regarding to A+T frequencies and AT and GC skews that also greatly diverge at the codon site and coding strand levels.

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Investigation of Two Evolutionarily Unrelated Halocarboxylic Acid Dehalogenase Gene Families

Journal of Bacteriology ◽

10.1128/jb.181.8.2535-2547.1999 ◽

1999 ◽

Vol 181 (8) ◽

pp. 2535-2547 ◽

Cited By ~ 72

Author(s):

Katja E. Hill ◽

Julian R. Marchesi ◽

Andrew J. Weightman

Keyword(s):

Amino Acid ◽

Molecular Analysis ◽

Phylogenetic Trees ◽

Gene Families ◽

Amino Acid Sequences ◽

Group I ◽

Silent Genes ◽

Degrading Bacteria ◽

Group Ii ◽

Almost All

ABSTRACT Dehalogenases are key enzymes in the metabolism of halo-organic compounds. This paper describes a systematic approach to the isolation and molecular analysis of two families of bacterial α-halocarboxylic acid (αHA) dehalogenase genes, called group I and group II deh genes. The two families are evolutionarily unrelated and together represent almost all of the αHAdeh genes described to date. We report the design and evaluation of degenerate PCR primer pairs for the separate amplification and isolation of group I and II dehgenes. Amino acid sequences derived from 10 of 11 group Ideh partial gene products of new and previously reported bacterial isolates showed conservation of five residues previously identified as essential for activity. The exception, DehD from a Rhizobium sp., had only two of these five residues. Group II deh gene sequences were amplified from 54 newly isolated strains, and seven of these sequences were cloned and fully characterized. Group II dehalogenases were stereoselective, dechlorinating l- but not d-2-chloropropionic acid, and derived amino acid sequences for all of the genes exceptdehII°P11 showed conservation of previously identified essential residues. Molecular analysis of the twodeh families highlighted four subdivisions in each, which were supported by high bootstrap values in phylogenetic trees and by enzyme structure-function considerations. Group Ideh genes included two putative cryptic or silent genes, dehI°PP3 anddehI°17a, produced by different organisms. Group II deh genes included two cryptic genes and an active gene, dehII PP3, that can be switched off and on. All αHA-degrading bacteria so far described were Proteobacteria, a result that may be explained by limitations either in the host range fordeh genes or in isolation methods.

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