{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T09:05:25Z","timestamp":1775639125950,"version":"3.50.1"},"reference-count":96,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T00:00:00Z","timestamp":1659830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG)","doi-asserted-by":"publisher","award":["STA 850\/51-2"],"award-info":[{"award-number":["STA 850\/51-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG)","doi-asserted-by":"publisher","award":["031A538B"],"award-info":[{"award-number":["031A538B"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"German Federal Ministry for Education and Research","doi-asserted-by":"publisher","award":["STA 850\/51-2"],"award-info":[{"award-number":["STA 850\/51-2"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"German Federal Ministry for Education and Research","doi-asserted-by":"publisher","award":["031A538B"],"award-info":[{"award-number":["031A538B"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Software"],"abstract":"<jats:p>AsymmeTree is a flexible and easy-to-use Python package for the simulation of gene family histories. It simulates species trees and considers the joint action of gene duplication, loss, conversion, and horizontal transfer to evolve gene families along the species tree. To generate realistic scenarios, evolution rate heterogeneity from various sources is modeled. Finally, nucleotide or amino acid sequences (optionally with indels, among-site rate heterogeneity, and invariant sites) can be simulated along the gene phylogenies. For all steps, users can choose from a spectrum of alternative methods and parameters. These choices include most options that are commonly used in comparable tools but also some that are usually not found, such as the innovation model for species evolution. While output files for each individual step can be generated, AsymmeTree is primarily intended to be integrated in complex Python pipelines designed to assess the performance of data analysis methods. It allows the user to interact with, analyze, and possibly manipulate the simulated scenarios. AsymmeTree is freely available on GitHub.<\/jats:p>","DOI":"10.3390\/software1030013","type":"journal-article","created":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T21:03:50Z","timestamp":1659906230000},"page":"276-298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["AsymmeTree: A Flexible Python Package for the Simulation of Complex Gene Family Histories"],"prefix":"10.3390","volume":"1","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0025-3097","authenticated-orcid":false,"given":"David","family":"Schaller","sequence":"first","affiliation":[{"name":"Bioinformatics Group, Department of Computer Science & Interdisciplinary Center for Bioinformatics, Leipzig University, H\u00e4rtelstra\u00dfe 16\u201318, D-04107 Leipzig, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1620-5508","authenticated-orcid":false,"given":"Marc","family":"Hellmuth","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Faculty of Science, Stockholm University, Roslagsv\u00e4gen 101, SE-10691 Stockholm, Sweden"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5016-5191","authenticated-orcid":false,"given":"Peter F.","family":"Stadler","sequence":"additional","affiliation":[{"name":"Bioinformatics Group, Department of Computer Science & Interdisciplinary Center for Bioinformatics, Leipzig University, H\u00e4rtelstra\u00dfe 16\u201318, D-04107 Leipzig, Germany"},{"name":"Max Planck Institute for Mathematics in the Sciences, Inselstra\u00dfe 22, D-04103 Leipzig, Germany"},{"name":"Department of Theoretical Chemistry, University of Vienna, W\u00e4hringerstra\u00dfe 17, A-1090 Wien, Austria"},{"name":"Facultad de Ciencias, Universidad National de Colombia, Bogot\u00e1 111321, Colombia"},{"name":"Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, NM 87501, USA"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ohno, S. (1970). Evolution by Gene Duplication, Springer.","DOI":"10.1007\/978-3-642-86659-3"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1093\/genetics\/151.4.1531","article-title":"Preservation of duplicate genes by complementary, degenerative mutations","volume":"151","author":"Force","year":"1999","journal-title":"Genetics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1126\/science.290.5494.1151","article-title":"The evolutionary fate and consequences of duplicate genes","volume":"290","author":"Lynch","year":"2000","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1093\/plcell\/koac076","article-title":"The multiple fates of gene duplications: Deletion, hypofunctionalization, subfunctionalization, neofunctionalization, dosage balance constraints, and neutral variation","volume":"34","author":"Birchler","year":"2022","journal-title":"Plant Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1126\/science.278.5338.631","article-title":"A genomic perspective on protein families","volume":"278","author":"Tatusov","year":"1997","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"27","DOI":"10.12688\/f1000research.21508.1","article-title":"Identifying orthologs with OMA: A primer","volume":"9","author":"Dessimoz","year":"2020","journal-title":"F1000Research"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"99","DOI":"10.2307\/2412448","article-title":"Distinguishing homologous from analogous proteins","volume":"19","author":"Fitch","year":"1970","journal-title":"Syst. Zool."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Roth, A.C.J., Gonnet, G.H., and Dessimoz, C. (2008). Algorithm of OMA for large-scale orthology inference. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-518"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s00285-012-0525-x","article-title":"Orthology Relations, Symbolic Ultrametrics, and Cographs","volume":"66","author":"Hellmuth","year":"2013","journal-title":"J. Math. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/nrg3456","article-title":"Functional and evolutionary implications of gene orthology","volume":"14","author":"Koonin","year":"2013","journal-title":"Nat. Rev. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/nmeth.3830","article-title":"Standardized benchmarking in the quest for orthologs","volume":"13","author":"Altenhoff","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3389\/fgene.2017.00165","article-title":"New Tools in Orthology Analysis: A Brief Review of Promising Perspectives","volume":"8","author":"Nichio","year":"2017","journal-title":"Front. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-7463-4_1","article-title":"Gene Phyologenies and Orthologous Groups","volume":"Volume 1704","author":"Setubal","year":"2018","journal-title":"Comparative Genomics"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Pascual-Anaya, J., D\u2019Aniello, S., Kuratani, S., and Garcia-Fern\u00e0ndez, J. (2013). Evolution of Hox gene clusters in deuterostomes. BMC Dev. Biol., 13.","DOI":"10.1186\/1471-213X-13-26"},{"key":"ref_15","first-page":"5","article-title":"From pairs of most similar sequences to phylogenetic best matches","volume":"15","author":"Stadler","year":"2020","journal-title":"Alg. Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s00285-021-01564-8","article-title":"Complete Characterization of Incorrect Orthology Assignments in Best Match Graphs","volume":"82","author":"Schaller","year":"2021","journal-title":"J. Math. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Talevich, E., Invergo, B.M., Cock, P.J., and Chapman, B.A. (2012). Bio.Phylo: A unified toolkit for processing, analyzing and visualizing phylogenetic trees in Biopython. BMC Bioinform., 13.","DOI":"10.1186\/1471-2105-13-209"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1093\/molbev\/msw046","article-title":"ETE 3: Reconstruction, Analysis, and Visualization of Phylogenomic Data","volume":"33","author":"Serra","year":"2016","journal-title":"Mol. Biol. Evol."},{"key":"ref_19","first-page":"23","article-title":"A simpler linear-time algorithm for the common refinement of rooted phylogenetic trees on a common leaf set","volume":"16","author":"Schaller","year":"2021","journal-title":"Alg. Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1137\/0210030","article-title":"Inferring a tree from lowest common ancestors with an application to the optimization of relational expressions","volume":"10","author":"Aho","year":"1981","journal-title":"SIAM J. Comput."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1007\/s00453-017-0330-4","article-title":"Fast Compatibility Testing for Rooted Phylogenetic Trees","volume":"80","author":"Deng","year":"2018","journal-title":"Algorithmica"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1250043","DOI":"10.1142\/S0219525912500439","article-title":"A model of macroevolution as a branching process based on innovations","volume":"15","author":"Klemm","year":"2012","journal-title":"Adv. Complex Syst."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1093\/sysbio\/syr029","article-title":"Simulating trees with a fixed number of extant species","volume":"60","author":"Stadler","year":"2011","journal-title":"Syst. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1534\/genetics.106.066951","article-title":"Consistent Patterns of Rate Asymmetry and Gene Loss Indicate Widespread Neofunctionalization of Yeast Genes After Whole-Genome Duplication","volume":"175","author":"Byrne","year":"2007","journal-title":"Genetics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1093\/sysbio\/syv082","article-title":"SimPhy: Phylogenomic Simulation of Gene, Locus, and Species Trees","volume":"65","author":"Mallo","year":"2016","journal-title":"Syst. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3496","DOI":"10.1093\/bioinformatics\/btz081","article-title":"SaGePhy: An improved phylogenetic simulation framework for gene and subgene evolution","volume":"35","author":"Kundu","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1214\/aoms\/1177730285","article-title":"On the Generalized \u201cBirth-and-Death\u201d Process","volume":"19","author":"Kendall","year":"1948","journal-title":"Ann. Math. Statist."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1111\/2041-210X.12917","article-title":"TreeSimGM: Simulating phylogenetic trees under general Bellman\u2013Harris models with lineage-specific shifts of speciation and extinction in R","volume":"9","author":"Hagen","year":"2018","journal-title":"Methods Ecol. Evol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1093\/bioinformatics\/btv651","article-title":"TESS: An R package for efficiently simulating phylogenetic trees and performing Bayesian inference of lineage diversification rates","volume":"32","author":"May","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1093\/bioinformatics\/btaa031","article-title":"Simulating trees with millions of species","volume":"36","author":"Louca","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_31","unstructured":"Felsenstein, J. (2004). Inferring Phylogenies, Sinauer Associates."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Yang, Z. (2006). Computational Molecular Evolution, Oxford University Press.","DOI":"10.1093\/acprof:oso\/9780198567028.001.0001"},{"key":"ref_33","first-page":"235","article-title":"Seq-Gen: An application for the Monte Carlo simulation of DNA sequence evolution along phylogenetic trees","volume":"13","author":"Rambaut","year":"1997","journal-title":"Comput. Appl. Biosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"iii31","DOI":"10.1093\/bioinformatics\/bti1200","article-title":"DNA assembly with gaps (Dawg): Simulating sequence evolution","volume":"21","author":"Cartwright","year":"2005","journal-title":"Bioinformatics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1093\/molbev\/msp098","article-title":"INDELible: A Flexible Simulator of Biological Sequence Evolution","volume":"26","author":"Fletcher","year":"2009","journal-title":"Mol. Biol. Evol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"msac092","DOI":"10.1093\/molbev\/msac092","article-title":"AliSim: A Fast and Versatile Phylogenetic Sequence Simulator for the Genomic Era","volume":"39","author":"Lanfear","year":"2022","journal-title":"Mol. Biol. Evol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Spielman, S.J., and Wilke, C.O. (2015). Pyvolve: A Flexible Python Module for Simulating Sequences along Phylogenies. PLoS ONE, 10.","DOI":"10.1101\/020214"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"642089","DOI":"10.1155\/2014\/642089","article-title":"Reconciliation of gene and species trees","volume":"2014","author":"Rusin","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/978-1-4939-9074-0_5","article-title":"Inferring Orthology and Paralogy","volume":"Volume 1910","author":"Anisimova","year":"2019","journal-title":"Evolutionary Genomics"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Sj\u00f6strand, J., Arvestad, L., Lagergren, J., and Sennblad, B. (2013). GenPhyloData: Realistic simulation of gene family evolution. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-209"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1093\/bioinformatics\/btz710","article-title":"Zombi: A phylogenetic simulator of trees, genomes and sequences that accounts for dead linages","volume":"36","author":"Tricou","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1093\/molbev\/msr268","article-title":"ALF\u2014A Simulation Framework for Genome Evolution","volume":"29","author":"Dalquen","year":"2012","journal-title":"Mol. Biol. Evol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1093\/bioinformatics\/16.2.101","article-title":"Darwin v. 2.0: An interpreted computer language for the biosciences","volume":"16","author":"Gonnet","year":"2000","journal-title":"Bioinformatics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4442","DOI":"10.1093\/bioinformatics\/btz424","article-title":"simuG: A general-purpose genome simulator","volume":"35","author":"Yue","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1093\/bioinformatics\/btx091","article-title":"Simulome: A genome sequence and variant simulator","volume":"33","author":"Price","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Pattnaik, S., Gupta, S., Rao, A.A., and Panda, B. (2014). SInC: An accurate and fast error-model based simulator for SNPs, Indels and CNVs coupled with a read generator for short-read sequence data. BMC Bioinform., 15.","DOI":"10.1186\/1471-2105-15-40"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Xu, Q., Jin, L., Leebens-Mack, J.H., and Sankoff, D. (2021). Validation of Automated Chromosome Recovery in the Reconstruction of Ancestral Gene Order. Algorithms, 14.","DOI":"10.3390\/a14060160"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1101\/gr.123901.111","article-title":"Unified modeling of gene duplication, loss, and coalescence using a locus tree","volume":"22","author":"Rasmussen","year":"2012","journal-title":"Genome Res."},{"key":"ref_49","first-page":"21","article-title":"A mathematical theory of evolution, based on the conclusions of Dr. J. C. Willis, F. R. S","volume":"213","author":"Yule","year":"1924","journal-title":"Phil. Trans. R. Soc. Lond. B"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/j.1096-0031.1989.tb00569.x","article-title":"Reconstructing character evolution on polytomous cladograms","volume":"5","author":"Maddison","year":"1989","journal-title":"Cladistics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/0169-5347(94)90034-5","article-title":"Speciation and phylogenetic resolution","volume":"9","author":"DeSalle","year":"1994","journal-title":"Trends Ecol. Evol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"932","DOI":"10.2307\/2640732","article-title":"Polytomies and the power of phylogenetic inference","volume":"53","author":"Walsh","year":"1999","journal-title":"Evolution"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"i519","DOI":"10.1093\/bioinformatics\/btu463","article-title":"Polytomy refinement for the correction of dubious duplications in gene trees","volume":"30","author":"Lafond","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.3389\/fpls.2019.01655","article-title":"Tackling Rapid Radiations with Targeted Sequencing","volume":"10","author":"Larridon","year":"2020","journal-title":"Front. Plant Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1093\/genetics\/156.4.1913","article-title":"The population genetics of the origin and divergence of the Drosophila simulans complex species","volume":"156","author":"Kliman","year":"2000","journal-title":"Genetics"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1093\/oxfordjournals.molbev.a003747","article-title":"Phylogenetic relationships and ancient incomplete lineage sorting among cichlid fishes in Lake Tanganyika as revealed by analysis of the insertion of retroposons","volume":"18","author":"Takahashi","year":"2001","journal-title":"Mol. Biol. Evol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Sayyari, E., and Mirarab, S. (2018). Testing for Polytomies in Phylogenetic Species Trees Using Quartet Frequencies. Genes, 9.","DOI":"10.3390\/genes9030132"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1086\/302221","article-title":"Concerted Evolution: Molecular Mechanisms and Biological Implications","volume":"64","author":"Liao","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1093\/dnares\/dsy005","article-title":"Functional divergence of duplicate genes several million years after gene duplication in Arabidopsis","volume":"25","author":"Hanada","year":"2018","journal-title":"DNA Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1146\/annurev.genom.1.1.99","article-title":"How Many Genes Can Make a Cell: The Minimal-Gene-Set Concept","volume":"1","author":"Koonin","year":"2000","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nrg.2017.74","article-title":"Emerging and evolving concepts in gene essentiality","volume":"19","author":"Rancati","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/nrmicro1234","article-title":"Mechanisms of, and barriers to, horizontal gene transfer between bacteria","volume":"3","author":"Thomas","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3309","DOI":"10.1093\/molbev\/mss138","article-title":"Replacing and Additive Horizontal Gene Transfer in Streptococcus","volume":"29","author":"Choi","year":"2012","journal-title":"Mol. Biol. Evol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Khayi, S., Blin, P., P\u00e9dron, J., Chong, T.M., Chan, K.G., Moumni, M., H\u00e9lias, V., Van Gijsegem, F., and Faure, D. (2015). Population genomics reveals additive and replacing horizontal gene transfers in the emerging pathogen Dickeya solani. BMC Genom., 16.","DOI":"10.1186\/s12864-015-1997-z"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Kordi, M., Kundu, S., and Bansal, M.S. (2019, January 7\u201310). On Inferring Additive and Replacing Horizontal Gene Transfers Through Phylogenetic Reconciliation. Proceedings of the 10th ACM International Conference on Bioinformatics, Computational Biology and Health Informatics, Niagara Falls, NY, USA.","DOI":"10.1145\/3307339.3342168"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1534\/genetics.107.072892","article-title":"Genetic exchange across a species boundary in the archaeal genus ferroplasma","volume":"177","author":"Eppley","year":"2007","journal-title":"Genetics"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1093\/gbe\/evs098","article-title":"Quantifying homologous replacement of loci between haloarchaeal species","volume":"4","author":"Williams","year":"2012","journal-title":"Genome Biol. Evol."},{"key":"ref_68","unstructured":"Kasha, M., and Pullman, B. (1962). Molecular disease, evolution, and genic heterogeneity. Horizons in Biochemistry, Academic Press."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Kawahara, Y., and Imanishi, T. (2007). A genome-wide survey of changes in protein evolutionary rates across four closely related species of Saccharomyces sensu stricto group. BMC Evol. Biol., 7.","DOI":"10.1186\/1471-2148-7-9"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4087","DOI":"10.1073\/pnas.90.9.4087","article-title":"Body size, metabolic rate, generation time, and the molecular clock","volume":"90","author":"Martin","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1073\/pnas.0407735101","article-title":"The Rate of DNA Evolution: Effects of Body Size and Temperature on the Molecular Clock","volume":"102","author":"Gillooly","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nrg2689","article-title":"The evolution of gene duplications: Classifying and distinguishing between models","volume":"11","author":"Innan","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1093\/molbev\/msm193","article-title":"A General Comparison of Relaxed Molecular Clock Models","volume":"24","author":"Lepage","year":"2007","journal-title":"Mol. Biol. Evol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1093\/oxfordjournals.molbev.a003811","article-title":"Performance of a Divergence Time Estimation Method under a Probabilistic Model of Rate Evolution","volume":"18","author":"Kishino","year":"2001","journal-title":"Mol. Biol. Evol."},{"key":"ref_75","unstructured":"Yang, Z. (2014). Molecular Evolution: A Statistical Approach, Oxford University Press. [1st ed.]."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","article-title":"SciPy 1.0: Fundamental Algorithms for Scientific Computing in Python","volume":"17","author":"Virtanen","year":"2020","journal-title":"Nat. Methods"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1021\/j100540a008","article-title":"Exact stochastic simulation of coupled chemical reactions","volume":"81","author":"Gillespie","year":"1977","journal-title":"J. Phys. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Jukes, T.H., and Cantor, C.R. (1969). Evolution of Protein Molecules. Mammalian Protein Metabolism, Elsevier.","DOI":"10.1016\/B978-1-4832-3211-9.50009-7"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/BF01731581","article-title":"A Simple Method for Estimating Evolutionary Rates of Base Substitutions through Comparative Studies of Nucleotide Sequences","volume":"16","author":"Kimura","year":"1980","journal-title":"J. Mol. Evol."},{"key":"ref_80","first-page":"57","article-title":"Some Probabilistic and Statistical Problems in the Analysis of DNA Sequences","volume":"17","year":"1986","journal-title":"Lect. Math. Life Sci."},{"key":"ref_81","unstructured":"Dayhoff, M., and Schwartz, R. (1978). A Model for Evolutionary Change in Proteins. Atlas of Protein Sequence and Structure, National Biomedical Research Foundation."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"10915","DOI":"10.1073\/pnas.89.22.10915","article-title":"Amino Acid Substitution Matrices from Protein Blocks","volume":"89","author":"Henikoff","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1093\/bioinformatics\/8.3.275","article-title":"The Rapid Generation of Mutation Data Matrices from Protein Sequences","volume":"8","author":"Jones","year":"1992","journal-title":"Bioinformatics"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1093\/oxfordjournals.molbev.a003851","article-title":"A General Empirical Model of Protein Evolution Derived from Multiple Protein Families Using a Maximum-Likelihood Approach","volume":"18","author":"Whelan","year":"2001","journal-title":"Mol. Biol. Evol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1093\/molbev\/msn067","article-title":"An Improved General Amino Acid Replacement Matrix","volume":"25","author":"Le","year":"2008","journal-title":"Mol. Biol. Evol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"319","DOI":"10.3389\/fgene.2015.00319","article-title":"Trends in substitution models of molecular evolution","volume":"6","author":"Arenas","year":"2015","journal-title":"Front. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"msac144","DOI":"10.1093\/molbev\/msac144","article-title":"Consequences of Substitution Model Selection on Protein Ancestral Sequence Reconstruction","volume":"39","author":"Arenas","year":"2022","journal-title":"Mol. Biol. Evol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1093\/bioinformatics\/13.5.555","article-title":"PAML: A Program Package for Phylogenetic Analysis by Maximum Likelihood","volume":"13","author":"Yang","year":"1997","journal-title":"Bioinformatics"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.jmb.2004.05.045","article-title":"Empirical Analysis of Protein Insertions and Deletions Determining Parameters for the Correct Placement of Gaps in Protein Sequence Alignments","volume":"341","author":"Chang","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_90","first-page":"1396","article-title":"Maximum-likelihood estimation of phylogeny from DNA sequences when substitution rates differ over sites","volume":"10","author":"Yang","year":"1993","journal-title":"Mol. Biol. Evol."},{"key":"ref_91","first-page":"546","article-title":"Maximum likelihood estimation of the heterogeneity of substitution rate among nucleotide sites","volume":"12","author":"Gu","year":"1995","journal-title":"Mol. Biol. Evol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1093\/bioinformatics\/18.3.502","article-title":"TREE-PUZZLE: Maximum likelihood phylogenetic analysis using quartets and parallel computing","volume":"18","author":"Schmidt","year":"2002","journal-title":"Bioinformatics"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s00285-021-01631-0","article-title":"Indirect Identification of Horizontal Gene Transfer","volume":"83","author":"Schaller","year":"2021","journal-title":"J. Math. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1093\/bioinformatics\/bti045","article-title":"Using shared genomic synteny and shared protein functions to enhance the identification of orthologous gene pairs","volume":"21","author":"Zheng","year":"2005","journal-title":"Bioinformatics"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Lechner, M., Hernandez-Rosales, M., Doerr, D., Wieseke, N., Th\u00e9venin, A., Stoye, J., Hartmann, R.K., Prohaska, S.J., and Stadler, P.F. (2014). Orthology Detection Combining Clustering and Synteny for Very Large Datasets. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105015"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Dohmen, E., Klasberg, S., Bornberg-Bauer, E., Perry, S., and Kemena, C. (2020). The modular nature of protein evolution: Domain rearrangement rates across eukaryotic life. BMC Evol. Biol., 20.","DOI":"10.1186\/s12862-020-1591-0"}],"container-title":["Software"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2674-113X\/1\/3\/13\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:05:21Z","timestamp":1760141121000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2674-113X\/1\/3\/13"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,7]]},"references-count":96,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["software1030013"],"URL":"https:\/\/doi.org\/10.3390\/software1030013","relation":{},"ISSN":["2674-113X"],"issn-type":[{"value":"2674-113X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,7]]}}}