Codon number shapes peptide redundancy in the universal proteome composition

Kusalik, Anthony; Trost, Brett; Bickis, Mik; Fasano, Candida; Capone, Giovanni; Kanduc, Darja

doi:10.1016/j.peptides.2009.06.035

Cited by 18 publications

(15 citation statements)

References 15 publications

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“…One group of scientists also introduced non-occurring peptide sequences into native proteins and observed little impact on overall protein expression, folding, and stability [25]. Another report suggested that the heat of formation of rare and non-occurring 5-mer peptides is not significantly different than more commonly occurring sequences [26]. The rate of energy expenditure appears to be restricted to a smaller range, indicating that natural peptide synthesis and assembly are not limiting factors and that there must be other biological reason that explain why certain 5-mer peptides do not occur in living organisms.…”

Section: Discussionmentioning

confidence: 99%

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Pentamers Not Found in the Universal Proteome Can Enhance Antigen Specific Immune Responses and Adjuvant Vaccines

et al. 2012

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Certain short peptides do not occur in humans and are rare or non-existent in the universal proteome. Antigens that contain rare amino acid sequences are in general highly immunogenic and may activate different arms of the immune system. We first generated a list of rare, semi-common, and common 5-mer peptides using bioinformatics tools to analyze the UniProtKB database. Experimental observations indicated that rare and semi-common 5-mers generated stronger cellular responses in comparison with common-occurring sequences. We hypothesized that the biological process responsible for this enhanced immunogenicity could be used to positively modulate immune responses with potential application for vaccine development. Initially, twelve rare 5-mers, 9-mers, and 13-mers were incorporated in frame at the end of an H5N1 hemagglutinin (HA) antigen and expressed from a DNA vaccine. The presence of some 5-mer peptides induced improved immune responses. Adding one 5-mer peptide exogenously also offered improved clinical outcome and/or survival against a lethal H5N1 or H1N1 influenza virus challenge in BALB/c mice and ferrets, respectively. Interestingly, enhanced anti-HBsAg antibody production by up to 25-fold in combination with a commercial Hepatitis B vaccine (Engerix-B, GSK) was also observed in BALB/c mice. Mechanistically, NK cell activation and dependency was observed with enhancing peptides ex vivo and in NK-depleted mice. Overall, the data suggest that rare or non-existent oligopeptides can be developed as immunomodulators and supports the further evaluation of some 5-mer peptides as potential vaccine adjuvants.

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Section: Discussionmentioning

confidence: 99%

“…At the start of this study, 1705 non-existing 5-mer peptides were identified from the universal proteome; however, this number decreased to 417 just recently [26]. All six of the 5-mer peptides initially selected for this study are now encoded in the proteome of one or more organisms (Table S1).…”

Section: Discussionmentioning

confidence: 99%

Pentamers Not Found in the Universal Proteome Can Enhance Antigen Specific Immune Responses and Adjuvant Vaccines

et al. 2012

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“…The origin of this bias is not entirely apparent, but it is likely to be evolutionary [ 14 ]. One study states that the codon number is related to this bias [ 27 ].…”

Section: Simple Frequency-based Approachmentioning

confidence: 99%

A Frequency-Based Linguistic Approach to Protein Decoding and Design: Simple Concepts, Diverse Applications, and the SCS Package

Motomura

Nakamura

Otaki

2013

Computational and Structural Biotechnology Journal

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Protein structure and function information is coded in amino acid sequences. However, the relationship between primary sequences and three-dimensional structures and functions remains enigmatic. Our approach to this fundamental biochemistry problem is based on the frequencies of short constituent sequences (SCSs) or words. A protein amino acid sequence is considered analogous to an English sentence, where SCSs are equivalent to words. Availability scores, which are defined as real SCS frequencies in the non-redundant amino acid database relative to their probabilistically expected frequencies, demonstrate the biological usage bias of SCSs. As a result, this frequency-based linguistic approach is expected to have diverse applications, such as secondary structure specifications by structure-specific SCSs and immunological adjuvants with rare or non-existent SCSs. Linguistic similarities (e.g., wide ranges of scale-free distributions) and dissimilarities (e.g., behaviors of low-rank samples) between proteins and the natural English language have been revealed in the rank-frequency relationships of SCSs or words. We have developed a web server, the SCS Package, which contains five applications for analyzing protein sequences based on the linguistic concept. These tools have the potential to assist researchers in deciphering structurally and functionally important protein sites, species-specific sequences, and functional relationships between SCSs. The SCS Package also provides researchers with a tool to construct amino acid sequences de novo based on the idiomatic usage of SCSs.

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“…Here, we define nullpeptides as sequences that are up to seven amino acids (aa) in length that are absent from the proteome. Previous work carried out in 2009 identified 417 five amino acid primes that are not present in the universal proteome (over 6 million proteins analyzed at that time) 6 . Functional characterization of a 5-mer peptide (KWCEC) that is extremely rare within the universal proteome and absent from the human proteome, showed that it could potentially enhance immunogenicity when administered alongside an antigen 7 .…”

Section: Introductionmentioning

confidence: 99%

Absent from DNA and protein: genomic characterization of nullomers and nullpeptides across functional categories and evolution

Georgakopoulos-Soares

Yizhar-Barnea

Mouratidis

et al. 2020

Preprint

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Nullomers and nullpeptides are short DNA or amino acid sequences that are absent from a genome or proteome, respectively. One potential cause for their absence could be that they have a detrimental impact on an organism. Here, we identified all possible nullomers and nullpeptides in the genomes and proteomes of over thirty species and show that a significant proportion of these sequences are under negative selection. We assign nullomers to different functional categories (coding sequences, exons, introns, 5'UTR, 3'UTR and promoters) and show that nullomers from coding sequences and promoters are most likely to be selected against. Utilizing variants in the human population, we annotate variant-associated nullomers, highlighting their potential use as DNA 'fingerprints'. Phylogenetic analyses of nullomers and nullpeptides across evolution shows that they could be used to build phylogenetic trees. Our work provides a catalog of genomic and proteome derived absent k-mers, together with a novel scoring function to determine their potential functional importance. In addition, it shows how these unique sequences could be used as DNA 'fingerprints' or for phylogenetic analyses.

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Codon number shapes peptide redundancy in the universal proteome composition

Cited by 18 publications

References 15 publications

Pentamers Not Found in the Universal Proteome Can Enhance Antigen Specific Immune Responses and Adjuvant Vaccines

Pentamers Not Found in the Universal Proteome Can Enhance Antigen Specific Immune Responses and Adjuvant Vaccines

A Frequency-Based Linguistic Approach to Protein Decoding and Design: Simple Concepts, Diverse Applications, and the SCS Package

Absent from DNA and protein: genomic characterization of nullomers and nullpeptides across functional categories and evolution

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