The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Accurate Detection of Convergent Mutations in Large Protein Alignments With ConDor
Published version of a preprint
Abstract
Evolutionary convergences are observed at all levels, from phenotype to DNA and protein sequences, and changes at these different levels tend to be correlated. Notably, convergent mutations can lead to convergent changes in phenotype, such as changes in metabolism, drug resistance, and other adaptations to changing environments. We propose a two-component approach to detect mutations subject to convergent evolution in protein alignments. The “Emergence” component selects mutations that emerge more often than expected, while the “Correlation” component selects mutations that correlate with the convergent phenotype under study. With regard to Emergence, a phylogeny deduced from the alignment is provided by the user and is used to simulate the evolution of each alignment position. These simulations allow us to estimate the expected number of mutations in a neutral model, which is compared to the observed number of mutations in the data studied. In Correlation, a comparative phylogenetic approach, is used to measure whether the presence of each of the observed mutations is correlated with the convergent phenotype. Each component can be used on its own, for example Emergence when no phenotype is available. Our method is implemented in a standalone workflow and a webserver, called ConDor. We evaluate the properties of ConDor using simulated data, and we apply it to three real datasets: sedge PEPC proteins, HIV reverse transcriptase, and fish rhodopsin. The results show that the two components of ConDor complement each other, with an overall accuracy that compares favorably to other available tools, especially on large datasets.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Computational accessibility can also be provided through publicly available web applications.
“Computational accessibility can also be provided through publicly available web applications (Ribeiro et al. 2023; Dong et al. 2024; Morel et al. 2024).”
From From Trees to Traits: A Review of Advances in PhyloG2P Methods and Future Directions (2025) · cites this paper as Morel et al. 2024
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Detecting Individual Sites Subject to Episodic Diversifying Selection
Murrell, B., Wertheim, J. O., Moola, S., Weighill, T., Scheffler, K., & Kosakovsky Pond, S. L. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002764 · Cited by 1,811
Spread of a SARS-CoV-2 variant through Europe in the summer of 2020
Hodcroft, E. B., Zuber, M., Nadeau, S., Vaughan, T. G., Crawford, K. H. D., Althaus, C. L., Reichmuth, M. L., Bowen, J. E., Walls, A. C., Corti, D., et al. (2021) · Nature · doi:10.1038/s41586-021-03677-y · Cited by 425
Martin, D. P., Weaver, S., Tegally, H., San, E. J., Shank, S. D., Wilkinson, E., Lucaci, A. G., Giandhari, J., Naidoo, S., Pillay, Y., et al. (2021) · doi:10.1101/2021.02.23.21252268 · Cited by 291 · cited 2×
“…where one first identified mutations in the Spike protein, which were spreading within the viral population and appeared multiple times independently, before being demonstrated to be evolutionarily advantageous for the virus (van Dorp et al. 2020; Korber et al. 2020; Martin et al. 2021).”
BackgroundFukushima, K., & Pollock, D. D. (2023) · Nature Ecology & Evolution · doi:10.1038/s41559-022-01932-7 · Cited by 55
Flagged first, then by citations
Research works printed but not linked: 102
- Arendt, 2008, Convergence and parallelism reconsidered: what have we learned about the genetics of adaptation?, Trends Ecol. Evol, 23, 26, 10.1016/j.tree.2007.09.011 · DOI
- Barker, 2005, Predicting functional gene links from phylogenetic—statistical analyses of whole genomes, PLoS Comput Biol., 1, e3, 10.1371/journal.pcbi.0010003 · DOI
- Besnard, 2009, Phylogenomics of C4 photosynthesis in sedges (Cyperaceae): multiple appearances and genetic convergence, Mol Biol Evol., 26, 1909, 10.1093/molbev/msp103 · DOI
- Bhattacharya, 2007, Founder effects in the assessment of HIV polymorphisms and HLA allele associations, Science, 315, 1583, 10.1126/science.1131528 · DOI
- Bläsing, 2000, Evolution of C4 phosphoenolpyruvate carboxylase in Flaveria, a conserved serine residue in the carboxyl-terminal part of the enzyme is a major determinant for C4-specific characteristics, J Biol Chem., 275, 27917, 10.1074/jbc.M909832199 · DOI
- Blassel, 2021, Using machine learning and big data to explore the drug resistance landscape in HIV, PLoS Comput Biol., 17, e1008873, 10.1371/journal.pcbi.1008873 · DOI
- Blassel, 2021, Drug resistance mutations in HIV: new bioinformatics approaches and challenges, Curr Opin Virol., 51, 56, 10.1016/j.coviro.2021.09.009 · DOI
- Bruhl, 2007, Towards a comprehensive survey of C3 and C4 photosynthetic pathways in Cyperaceae, Aliso, 23, 99, 10.5642/aliso.20072301.11 · DOI
- Castoe, 2009, Evidence for an ancient adaptive episode of convergent molecular evolution, Proc Natl Acad Sci, 106, 8986, 10.1073/pnas.0900233106 · DOI
- Chabrol, 2018, Detecting the molecular basis of phenotypic convergence, Methods Ecol Evol, 9, 2170, 10.1111/2041-210X.13071 · DOI
- Chai, 2020, Evidence of echolocation in the common shrew from molecular convergence with other echolocating mammals, Zool Stud, 59, e4
- Chang, 2014, TCS: a new multiple sequence alignment reliability measure to estimate alignment accuracy and improve phylogenetic tree reconstruction, Mol Biol Evol., 31, 1625, 10.1093/molbev/msu117 · DOI
- Christin, 2007, C4 photosynthesis evolved in grasses via parallel adaptive genetic changes, Curr Biol., 17, 1241, 10.1016/j.cub.2007.06.036 · DOI
- Cock, 2009, Biopython: freely available Python tools for computational molecular biology and bioinformatics, Bioinformatics, 25, 1422, 10.1093/bioinformatics/btp163 · DOI · Paper page
- Crandall, 1999, Parallel evolution of drug resistance in HIV: failure of nonsynonymous/synonymous substitution rate ratio to detect selection, Mol Biol Evol., 16, 372, 10.1093/oxfordjournals.molbev.a026118 · DOI
- Cuevas, 2002, Molecular basis of adaptive convergence in experimental populations of RNA viruses, Genetics, 162, 533, 10.1093/genetics/162.2.533 · DOI
- Davies, 2012, Parallel signatures of sequence evolution among hearing genes in echolocating mammals: an emerging model of genetic convergence, Heredity (Edinb)., 108, 480, 10.1038/hdy.2011.119 · DOI · Paper page
- Duchemin, 2023, Evaluation of methods to detect shifts in directional selection at the genome scale, Mol Biol Evol., 40, msac247, 10.1093/molbev/msac247 · DOI
- Ehleringer, 1997, C4 photosynthesis, atmospheric CO2, and climate, Oecologia, 112, 285, 10.1007/s004420050311 · DOI
- Escalera-Zamudio, 2020, Parallel evolution in the emergence of highly pathogenic avian influenza A viruses, Nat Commun., 11, 5511, 10.1038/s41467-020-19364-x · DOI
- Fitch, 1971, Toward defining the course of evolution: minimum change for a specific tree topology, Syst Biol., 20, 406, 10.1093/sysbio/20.4.406 · DOI
- Foll, 2014, Widespread signals of convergent adaptation to high altitude in Asia and America, Am J Hum Genet., 95, 394, 10.1016/j.ajhg.2014.09.002 · DOI
- Foote, 2015, Convergent evolution of the genomes of marine mammals, Nat Genet., 47, 272, 10.1038/ng.3198 · DOI
- Gascuel, 2014, Predicting the ancestral character changes in a tree is typically easier than predicting the root state, Syst Biol., 63, 421, 10.1093/sysbio/syu010 · DOI
- Goldman, 1994, A codon-based model of nucleotide substitution for protein-coding DNA sequences, Mol Biol Evol., 11, 725
- Goldstein, 2015, Nonadaptive amino acid convergence rates decrease over time, Mol Biol Evol., 32, 1373, 10.1093/molbev/msv041 · DOI
- Gutierrez, 2019, Parallel molecular evolution and adaptation in viruses, Curr Opin Virol., 34, 90, 10.1016/j.coviro.2018.12.006 · DOI
- Harris, 2020, Array programming with NumPy, Nature, 585, 357, 10.1038/s41586-020-2649-2 · DOI · Paper page
- Hill, 2019, Recurrent convergent evolution at amino acid residue 261 in fish rhodopsin, Proc. Natl. Acad. Sci, 116, 18473, 10.1073/pnas.1908332116 · DOI
- Hoang, 2018, UFBoot2: improving the ultrafast bootstrap approximation, Mol Biol Evol., 35, 518, 10.1093/molbev/msx281 · DOI · Paper page
- Holm, 1979, A simple sequentially rejective multiple test procedure, Scand. J. Stat, 6, 65
- Holmes, 1992, Convergent and divergent sequence evolution in the surface envelope glycoprotein of human immunodeficiency virus type 1 within a single infected patient, Proc Natl Acad Sci U S A., 89, 4835, 10.1073/pnas.89.11.4835 · DOI
- Hu, 2017, Comparative genomics reveals convergent evolution between the bamboo-eating giant and red pandas, Proc Natl Acad Sci U S A, 114, 1081, 10.1073/pnas.1613870114 · DOI
- Huerta-Cepas, 2016, ETE 3: reconstruction, analysis, and visualization of phylogenomic data, Mol Biol Evol., 33, 1635, 10.1093/molbev/msw046 · DOI
- Hunter, 2007, Matplotlib: a 2D graphics environment, Comput Sci Eng., 9, 90, 10.1109/MCSE.2007.55 · DOI · Paper page
- Ishikawa, 2019, A fast likelihood method to reconstruct and visualize ancestral scenarios, Mol Biol Evol., 36, 2069, 10.1093/molbev/msz131 · DOI
- Jones, 1992, The rapid generation of mutation data matrices from protein sequences, Bioinformatics, 8, 275, 10.1093/bioinformatics/8.3.275 · DOI
- Kalyaanamoorthy, 2017, ModelFinder: fast model selection for accurate phylogenetic estimates, Nat Methods., 14, 587, 10.1038/nmeth.4285 · DOI · Paper page
- Kass, 1995, Bayes factors, J Am Stat Assoc., 90, 773, 10.1080/01621459.1995.10476572 · DOI · Paper page
- Korber, 2020, Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus, Cell, 182, 812, 10.1016/j.cell.2020.06.043 · DOI · Paper page
- Kusagawa, 2001, Isolation and characterization of a full-length molecular DNA clone of Ghanaian HIV type 1 intersubtype A/G recombinant CRF02_AG, which is replication competent in a restricted host range, AIDS Res Hum Retroviruses, 17, 649, 10.1089/088922201300119761 · DOI
- Larter, 2018, Convergent evolution at the pathway level: predictable regulatory changes during flower color transitions, Mol Biol Evol., 35, 2159, 10.1093/molbev/msy117 · DOI
- Lartillot, 2004, A Bayesian mixture model for across-site heterogeneities in the amino-acid replacement process, Mol Biol Evol., 21, 1095, 10.1093/molbev/msh112 · DOI · Paper page
- Le, 2012, Modeling protein evolution with several amino acid replacement matrices depending on site rates, Mol Biol Evol., 29, 2921, 10.1093/molbev/mss112 · DOI
- Le, 2008, Empirical profile mixture models for phylogenetic reconstruction, Bioinformatics, 24, 2317, 10.1093/bioinformatics/btn445 · DOI
- Le, 2008, Phylogenetic mixture models for proteins, Philos. Trans. R. Soc. B Biol. Sci, 363, 3965, 10.1098/rstb.2008.0180 · DOI
- Lemey, 2005, Molecular footprint of drug-selective pressure in a human immunodeficiency virus transmission chain, J Virol., 79, 11981, 10.1128/JVI.79.18.11981-11989.2005 · DOI
- Lemoine, 2021, Gotree/Goalign: toolkit and Go API to facilitate the development of phylogenetic workflows, NAR Genom Bioinform, 3, lqab07
- Longdon, 2018, Host shifts result in parallel genetic changes when viruses evolve in closely related species, PLoS Pathog, 14, e1006951, 10.1371/journal.ppat.1006951 · DOI
- Losos, 2011, Convergence, adaptation, and constraint, Evolution, 65, 1827, 10.1111/j.1558-5646.2011.01289.x · DOI
- Lu, 2020, Molecular convergent and parallel evolution among four high-elevation anuran species from the Tibetan region, BMC Genomics, 21, 839, 10.1186/s12864-020-07269-4 · DOI
- Malinsky, 2015, Genomic islands of speciation separate cichlid ecomorphs in an east African crater lake, Science, 350, 1493, 10.1126/science.aac9927 · DOI
- Marcovitz, 2019, A functional enrichment test for molecular convergent evolution finds a clear protein-coding signal in echolocating bats and whales, Proc Natl Acad Sci U S A., 116, 21094, 10.1073/pnas.1818532116 · DOI
- Martin, 2021, The emergence and ongoing convergent evolution of the SARS-CoV-2 N501Y lineages, Cell, 184, 5189, 10.1016/j.cell.2021.09.003 · DOI
- Murrell, 2012, Modeling HIV-1 drug resistance as episodic directional selection, PLoS Comput Biol., 8, e1002507, 10.1371/journal.pcbi.1002507 · DOI
- Murrell, 2013, FUBAR: a fast, unconstrained Bayesian AppRoximation for inferring selection, Mol Biol Evol., 30, 1196, 10.1093/molbev/mst030 · DOI
- Muschick, 2012, Convergent evolution within an adaptive radiation of cichlid fishes, Curr Biol., 22, 2362, 10.1016/j.cub.2012.10.048 · DOI
- Nguyen, 2015, IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies, Mol Biol Evol., 32, 268, 10.1093/molbev/msu300 · DOI · Paper page
- Nickle, 2007, HIV-Specific Probabilistic models of protein evolution, PLoS One, 2, e503, 10.1371/journal.pone.0000503 · DOI
- O’Reilly, 2016, Bayesian methods outperform parsimony but at the expense of precision in the estimation of phylogeny from discrete morphological data, Biol Lett., 12, 20160081, 10.1098/rsbl.2016.0081 · DOI · Paper page
- Pagel, 1994, Detecting correlated evolution on phylogenies: a general method for the comparative analysis of discrete characters, Proc R Soc Lond B Biol Sci, 255, 37, 10.1098/rspb.1994.0006 · DOI · Paper page
- Pagel, 2006, Bayesian analysis of correlated evolution of discrete characters by reversible-jump Markov chain Monte Carlo, Am Nat., 167, 808, 10.1086/503444 · DOI · Paper page
- Paradis, 2004, APE: analyses of phylogenetics and evolution in R language, Bioinformatics, 20, 289, 10.1093/bioinformatics/btg412 · DOI · Paper page
- Parker, 2013, Genome-wide signatures of convergent evolution in echolocating mammals, Nature, 502, 228, 10.1038/nature12511 · DOI
- Parto, 2017, Detecting consistent patterns of directional adaptation using differential selection codon models, BMC Evol Biol, 17, 147, 10.1186/s12862-017-0979-y · DOI
- Parto, 2018, Molecular adaptation in Rubisco: discriminating between convergent evolution and positive selection using mechanistic and classical codon models, PLoS One, 13, e0192697, 10.1371/journal.pone.0192697 · DOI
- Pond, 2005, Hyphy: hypothesis testing using phylogenies, Bioinformatics, 21, 676, 10.1093/bioinformatics/bti079 · DOI · Paper page
- Pond, 2012, Evolution of viral genomes: interplay between selection, recombination, and other forces, Methods Mol Biol, 856, 239, 10.1007/978-1-61779-585-5_10 · DOI
- Price, 2009, FastTree: computing large minimum evolution trees with profiles instead of a distance matrix, Mol Biol Evol., 26, 1641, 10.1093/molbev/msp077 · DOI · Paper page
- Rey, 2018, Accurate detection of convergent amino-acid evolution with PCOC, Mol Biol Evol., 35, 2296, 10.1093/molbev/msy114 · DOI · Paper page
- Rey, 2019, Detecting adaptive convergent amino acid evolution, Philos Trans R Soc B Biol Sci, 374, 20180234, 10.1098/rstb.2018.0234 · DOI
- Rhee, 2003, Human immunodeficiency virus reverse transcriptase and protease sequence database, Nucleic Acids Res, 31, 298, 10.1093/nar/gkg100 · DOI
- Rokas, 2008, Frequent and widespread parallel evolution of protein sequences, Mol Biol Evol., 25, 1943, 10.1093/molbev/msn143 · DOI
- Rosenblum, 2014, The molecular basis of phenotypic convergence, Annu Rev Ecol Evol Syst., 45, 203, 10.1146/annurev-ecolsys-120213-091851 · DOI · Paper page
- Schultz, 2012, jpHMM: recombination analysis in viruses with circular genomes such as the hepatitis B virus, Nucleic Acids Res, 40, W193, 10.1093/nar/gks414 · DOI
- Sluis-Cremer, 2014, E138a in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings, Antiviral Res, 107, 31, 10.1016/j.antiviral.2014.04.001 · DOI
- Soubrier, 2012, The influence of rate heterogeneity among sites on the time dependence of molecular rates, Mol Biol Evol., 29, 3345, 10.1093/molbev/mss140 · DOI
- Spady, 2005, Adaptive molecular evolution in the opsin genes of rapidly speciating cichlid species, Mol Biol Evol., 22, 1412, 10.1093/molbev/msi137 · DOI
- Starr, 2020, Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding, Cell, 182, 1295, 10.1016/j.cell.2020.08.012 · DOI · Paper page
- Stern, 2013, The genetic causes of convergent evolution, Nat Rev Genet., 14, 751, 10.1038/nrg3483 · DOI · Paper page
- Stoltzfus, 2017, Mutational biases influence parallel adaptation, Mol Biol Evol., 34, 2163, 10.1093/molbev/msx180 · DOI
- Storz, 2016, Causes of molecular convergence and parallelism in protein evolution, Nat Rev Genet., 17, 239, 10.1038/nrg.2016.11 · DOI
- Susko, 2003, Estimation of rates-across-sites distributions in phylogenetic substitution models, Syst Biol., 52, 594, 10.1080/10635150390235395 · DOI
- Svensson, 2003, Evolution of C4 phosphoenolpyruvate carboxylase, Arch Biochem Biophys., 414, 180, 10.1016/S0003-9861(03)00165-6 · DOI
- Tamuri, 2009, Identifying changes in selective constraints: host shifts in influenza, PLoS Comput Biol., 5, e1000564, 10.1371/journal.pcbi.1000564 · DOI
- Thomas, 2015, Determining the null model for detecting adaptive convergence from genomic data: a case study using echolocating mammals, Mol Biol Evol., 32, 1232, 10.1093/molbev/msv013 · DOI
- Tommaso, 2017, Nextflow enables reproducible computational workflows, Nat Biotechnol., 35, 316, 10.1038/nbt.3820 · DOI · Paper page
- Tsetsarkin, 2007, A single mutation in chikungunya virus affects vector specificity and epidemic potential, PLoS Pathog, 3, e201, 10.1371/journal.ppat.0030201 · DOI
- Ujvari, 2015, Widespread convergence in toxin resistance by predictable molecular evolution, Proc Natl Acad Sci U S A, 112, 11911, 10.1073/pnas.1511706112 · DOI
- van Ditmarsch, 2013, Convergent evolution of hyperswarming leads to impaired biofilm formation in pathogenic bacteria, Cell Rep, 4, 697, 10.1016/j.celrep.2013.07.026 · DOI
- van Dorp, 2020, Emergence of genomic diversity and recurrent mutations in SARS-CoV-2, Infect Genet Evol., 83, 104351, 10.1016/j.meegid.2020.104351 · DOI
- Villabona-Arenas, 2016, In-depth analysis of HIV-1 drug resistance mutations in HIV-infected individuals failing first-line regimens in West and Central Africa, AIDS, 30, 2577, 10.1097/QAD.0000000000001233 · DOI
- Virtanen, 2020, Scipy 1.0: fundamental algorithms for scientific computing in Python, Nat Methods., 17, 261, 10.1038/s41592-019-0686-2 · DOI · Paper page
- Waskom, 2021, Seaborn: statistical data visualization, J. Open Source Softw, 6, 3021, 10.21105/joss.03021 · DOI · Paper page
- Wensing, 2019, 2019 update of the drug resistance mutations in HIV-1, Top Antivir Med., 27, 111
- Xu, 2020, Genomic convergence in the adaptation to extreme environments, Plant Commun, 1, 100117, 10.1016/j.xplc.2020.100117 · DOI
- Yokoyama, 2008, Evolution of dim-light and color vision pigments, Annu Rev Genom Hum Genet, 9, 259, 10.1146/annurev.genom.9.081307.164228 · DOI
- Zhang, 2006, Parallel adaptive origins of digestive RNases in Asian and African leaf monkeys, Nat Genet., 38, 819, 10.1038/ng1812 · DOI
- Zhang, 1997, Detection of convergent and parallel evolution at the amino acid sequence level, Mol Biol Evol., 14, 527, 10.1093/oxfordjournals.molbev.a025789 · DOI
- Zhen, 2012, Parallel molecular evolution in an herbivore community, Science, 337, 1634, 10.1126/science.1226630 · DOI · Paper page
- Zou, 2015, Are convergent and parallel amino acid substitutions in protein evolution more prevalent than neutral expectations?, Mol Biol Evol., 32, 2085, 10.1093/molbev/msv091 · DOI · Paper page
- Zou, 2015, No genome-wide protein sequence convergence for echolocation, Mol Biol Evol., 32, 1237, 10.1093/molbev/msv014 · DOI
Cited by
Sorted by citations
From Trees to Traits: A Review of Advances in PhyloG2P Methods and Future Directions
Macdonald, A. R., James, M. E., Mitchell, J. D., & Holland, B. R. (2025) · Genome Biology and Evolution · doi:10.1093/gbe/evaf150 · Cited by 5
Metadata
- Authors
- Morel, M., Zhukova, A., Lemoine, F., & Gascuel, O.
- Affiliations
- Institut Pasteur, Université Paris Cité, Unité Bioinformatique Evolutive , Paris , France
- Venue
- Genome Biology and Evolution
- Publisher
- Oxford University Press (OUP)
- Published
- 2024-03-07
- Volume
- 16
- Issue
- 4
- ISSN
- 1759-6653
- PMC
- PMC10986858
- Cited by
- 3
- References
- 4
- Language
- en
- Funders
- INCEPTION (ANR-16-CONV-0005)
- PRAIRIE (ANR-19-P3IA-0001)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review