Amino Acid Metabolism Conflicts with Protein Diversity

Krick, Teresa; Verstraete, Nina; Alonso, Leonardo G.; Shub, David A.; Ferreiro, Diego U.; Shub, Michael; Sánchez, Ignacio E.

doi:10.1093/molbev/msu228

Cited by 47 publications

(63 citation statements)

References 31 publications

(65 reference statements)

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“…Set 1 contains eight basic physicochemical descriptors of the amino acids: volume , log(solubility) , hydrophobicity , isoelectric point , helix propensity , steric hindrance , flexibility and sheet propensity. Set 2 contains two metrics related to the metabolic cost of the amino acids both having larger values for metabolically more expensive amino acids [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

Detection and sequence/structure mapping of biophysical constraints to protein variation in saturated mutational libraries and protein sequence alignments with a dedicated server

2016

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BackgroundProtein variability can now be studied by measuring high-resolution tolerance-to-substitution maps and fitness landscapes in saturated mutational libraries. But these rich and expensive datasets are typically interpreted coarsely, restricting detailed analyses to positions of extremely high or low variability or dubbed important beforehand based on existing knowledge about active sites, interaction surfaces, (de)stabilizing mutations, etc.ResultsOur new webserver PsychoProt (freely available without registration at http://psychoprot.epfl.ch or at http://lucianoabriata.altervista.org/psychoprot/index.html) helps to detect, quantify, and sequence/structure map the biophysical and biochemical traits that shape amino acid preferences throughout a protein as determined by deep-sequencing of saturated mutational libraries or from large alignments of naturally occurring variants.DiscussionWe exemplify how PsychoProt helps to (i) unveil protein structure-function relationships from experiments and from alignments that are consistent with structures according to coevolution analysis, (ii) recall global information about structural and functional features and identify hitherto unknown constraints to variation in alignments, and (iii) point at different sources of variation among related experimental datasets or between experimental and alignment-based data. Remarkably, metabolic costs of the amino acids pose strong constraints to variability at protein surfaces in nature but not in the laboratory. This and other differences call for caution when extrapolating results from in vitro experiments to natural scenarios in, for example, studies of protein evolution.ConclusionWe show through examples how PsychoProt can be a useful tool for the broad communities of structural biology and molecular evolution, particularly for studies about protein modeling, evolution and design.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1124-4) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Detection and sequence/structure mapping of biophysical constraints to protein variation in saturated mutational libraries and protein sequence alignments with a dedicated server

2016

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“…This allows insights in protein abundance evolution, such as abundance conservation in the eukaryotic core proteome [21,25,26], cost-diversity tradeoffs during evolution [27], or the fate of paralogs during evolutionary network rewiring [28]. Orthology relationships in PaxDb are precomputed, through the eggNOG mechanism [29], and can be browsed at various levels of phylogenetic depth (e.g.…”

Section: Stoichiometries and Abundances On The Tree Of Lifementioning

confidence: 99%

Version 4.0 of PaxDb: Protein abundance data, integrated across model organisms, tissues, and cell‐lines

et al. 2015

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Protein quantification at proteome-wide scale is an important aim, enabling insights into fundamental cellular biology and serving to constrain experiments and theoretical models. While proteome-wide quantification is not yet fully routine, many datasets approaching proteomewide coverage are becoming available through biophysical and MS techniques. Data of this type can be accessed via a variety of sources, including publication supplements and online data repositories. However, access to the data is still fragmentary, and comparisons across experiments and organisms are not straightforward. Here, we describe recent updates to our database resource "PaxDb" (Protein Abundances Across Organisms). PaxDb focuses on protein abundance information at proteome-wide scope, irrespective of the underlying measurement technique. Quantification data is reprocessed, unified, and quality-scored, and then integrated to build a meta-resource. PaxDb also allows evolutionary comparisons through precomputed gene orthology relations. Recently, we have expanded the scope of the database to include cell-line samples, and more systematically scan the literature for suitable datasets. We report that a significant fraction of published experiments cannot readily be accessed and/or parsed for quantitative information, requiring additional steps and efforts. The current update brings PaxDb to 414 datasets in 53 organisms, with (semi-) quantitative abundance information covering more than 300 000 proteins.

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“…Hence avoidance of metabolic costs (Akashi and Gojobori, 2002; Seligmann, 2003, 2012b; Brocchieri and Karlin, 2005; Warringer and Blomberg, 2006; Heizer et al, 2011; Chen and Bundschuh, 2012; Raiford et al, 2012; Krick et al, 2014; Chen W.-H. et al, 2016) should favor evolution of linear consensus signals. Consequently, linear signals presumably evolved more recently to become punctuation marks with higher accuracy, specialization, and metabolic efficiency than structural signals.…”

Section: Introductionmentioning

confidence: 99%

Evolution of Nucleotide Punctuation Marks: From Structural to Linear Signals

Houmami

Seligmann

2017

Front. Genet.

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We present an evolutionary hypothesis assuming that signals marking nucleotide synthesis (DNA replication and RNA transcription) evolved from multi- to unidimensional structures, and were carried over from transcription to translation. This evolutionary scenario presumes that signals combining secondary and primary nucleotide structures are evolutionary transitions. Mitochondrial replication initiation fits this scenario. Some observations reported in the literature corroborate that several signals for nucleotide synthesis function in translation, and vice versa. (a) Polymerase-induced frameshift mutations occur preferentially at translational termination signals (nucleotide deletion is interpreted as termination of nucleotide polymerization, paralleling the role of stop codons in translation). (b) Stem-loop hairpin presence/absence modulates codon-amino acid assignments, showing that translational signals sometimes combine primary and secondary nucleotide structures (here codon and stem-loop). (c) Homopolymer nucleotide triplets (AAA, CCC, GGG, TTT) cause transcriptional and ribosomal frameshifts. Here we find in recently described human mitochondrial RNAs that systematically lack mono-, dinucleotides after each trinucleotide (delRNAs) that delRNA triplets include 2x more homopolymers than mitogenome regions not covered by delRNA. Further analyses of delRNAs show that the natural circular code X (a little-known group of 20 translational signals enabling ribosomal frame retrieval consisting of 20 codons {AAC, AAT, ACC, ATC, ATT, CAG, CTC, CTG, GAA, GAC, GAG, GAT, GCC, GGC, GGT, GTA, GTC, GTT, TAC, TTC} universally overrepresented in coding versus other frames of gene sequences), regulates frameshift in transcription and translation. This dual transcription and translation role confirms for X the hypothesis that translational signals were carried over from transcriptional signals.

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Amino Acid Metabolism Conflicts with Protein Diversity

Cited by 47 publications

References 31 publications

Detection and sequence/structure mapping of biophysical constraints to protein variation in saturated mutational libraries and protein sequence alignments with a dedicated server

Detection and sequence/structure mapping of biophysical constraints to protein variation in saturated mutational libraries and protein sequence alignments with a dedicated server

Version 4.0 of PaxDb: Protein abundance data, integrated across model organisms, tissues, and cell‐lines

Evolution of Nucleotide Punctuation Marks: From Structural to Linear Signals

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