Integrating Molecular Evolution and Computational Biology: Bridging Disciplines for Future Research
DOI:
https://doi.org/10.63635/mrj.v1i3.109Keywords:
Molecular evolution, Single Nuelcotide Variations, Selection, Codon Usage Bias, Computational BiologyAbstract
Molecular evolution, conventionally rooted in classical evolutionary theory and comparative biology, has entered a transformative era driven by advances in genomics, bioinformatics, and computational modeling. This review traces the conceptual foundations of molecular evolution, beginning with the central dogma and codon degeneracy, and explores how variations such as single nucleotide variants (SNVs) shape protein structure and function. It highlights the evolutionary implications of codon usage bias, substitution models, and the mutation and selection balance in across genomes. Recent advances in artificial intelligence (AI), machine learning, biostatistics, and mathematical modeling have revolutionized our understanding of molecular evolution. AI-driven approaches and mathematical algorithms enhance analyses of genetic variation, protein evolution, and evolutionary dynamics. Updated computational platforms such as IQ-TREE 2, RAxML-NG, BEAST 2, PAML, and HyPhy, along with R and Python-based pipelines, have revolutionized evolutionary studies by enabling accurate modeling of mutation dynamics, phylogenetic reconstructions, and selection analyses.Additionally, the chemistry of amino acid exchangeability introduces new perspectives in evolutionary studies. This convergence of computational biology with mathematics, chemistry, and data science has transformed evolutionary biology into a multidisciplinary and collaborative research area to solve long standing biological queries. This opens up opportunities for a successful career in multidisciplinary research in evolutionary biology.
Downloads
References
[1] Nirenberg, M. W.; The genetic code; Scientific American1963, 208(3), 80-95.
[2] Crick, F.; Francis Crick. The Double Helix; acta crystallographia 1951, 2-3.
[3] Watson, J. D.; Crick, F. H. C.; On protein synthesis; The Symposia of the Society for Experimental Biology1958, 12, 138-163.
[4] Crick, F.; Central dogma of molecular biology; Nature1970, 227(5258), 561-563; https://doi.org/10.1038/227561a0
[5] Gadgil, M.; Bossert, W. H.; Life historical consequences of natural selection; The American Naturalist1970, 104(935), 1-24; https://doi.org/10.1086/282638
[6] Gibbs, H. L.; Grant, P. R.; Oscillating selection on Darwin's finches; Nature1987, 327(6122), 511-513; https://doi.org/10.1038/327511a0
[7] Fisher, R. A.; XV. —The correlation between relatives on the supposition of Mendelian inheritance; Earth and Environmental Science Transactions of the Royal Society of Edinburgh1919, 52(2), 399-433; https://doi.org/10.1017/S0080456800012163
[8] Berry, A.; Browne, J.; Mendel and Darwin; Proceedings of the National Academy of Sciences2022, 119(30), e2122144119; https://doi.org/10.1073/pnas.2122144119
[9] Dawkins, R.; The Blind Watchmaker Norton & Company: New York, NY, USA, 1986 ISBN: 978-0393351491.
[10] Esposito, M.; From human science to biology: The second synthesis of Ronald Fisher; History of the Human Sciences 2016, 29(3), 44-62; https://doi.org/10.1177/0952695116645958
[11] Hardy, G. H.; Mendelian proportions in a mixed population; Science; 1908 28(706), 49-50; https://doi.org/10.1126/science.28.706.49
[12] Stern, C.; The Hardy-Weinberg law; Science 1943, 97(2510), 137-138; https://doi.org/10.1126/science.97.2510.137
[13] Mayr, E.; Animal Species and Evolution; Harvard University Press: Cambridge, MA, USA, 1963
[14] Chandler, A. C.; The effect of extent of distribution on speciation; The American Naturalist1914, 48(567), 129-160; https://doi.org/10.1086/279445
[15] Simpson, G. G.; The Major Features of Evolution; Columbia University Press: New York, NY, USA, 1953.
[16] Stanley, S. M.; A theory of evolution above the species level; Proceedings of the National Academy of Sciences1975, 72(2), 646-650; https://doi.org/10.1073/pnas.72.2.646
[17] Boyden, A.; Homology and analogy: A critical review of the meanings and implications of these concepts in biology; American Midland Naturalist1947, 648-669; https://doi.org/10.2307/2421727
[18] Zangerl, R.; The methods of comparative anatomy and its contribution to the study of evolution; Evolution1948, 351-374; https://doi.org/10.2307/2405743
[19] Goodhart, C. B.; The Sewall Wright Effect; The American Naturalist1963, 97(897), 407-409; https://doi.org/10.1086/282295
[20] Watson, J. D.; Crick, F. H. C.; The structure of DNA; Cold Spring Harbor Symposia on Quantitative Biology1953, 18, 123-131; https://doi.org/10.1101/SQB.1953.018.01.020
[21] Jumper, J.; Evans, R.; Pritzel, A.; Green, T.; Figurnov, M.; Ronneberger, O.; Hassabis, D.; Highly accurate protein structure prediction with AlphaFold; Nature2021, 596(7873), 583-589; https://doi.org/10.1038/s41586-021-03819-2
[22] Crick, F.; Chapter 8: The genetic code; In What Mad Pursuit: A Personal View of Scientific Discovery Basic Books: New York, NY, USA, 1988; pp. 89-101.
[23] Ikemura, T.; Codon usage and tRNA content in unicellular and multicellular organisms; Molecular Biology and Evolution1985, 2(1), 13-34; https://doi.org/10.1093/oxfordjournals.molbev.a040343
[24] Gouy, M.; Gautier, C.; Codon usage in bacteria: Correlation with gene expressivity; Nucleic Acids Research1982, 10(22), 7055-7074; https://doi.org/10.1093/nar/10.22.7055
[25] McInerney, J. O.; Replicational and transcriptional selection on codon usage in Borrelia burgdorferi; Proceedings of the National Academy of Sciences1998, 95(18), 10698-10703; https://doi.org/10.1073/pnas.95.18.10698
[26] Seward, E. A.; Kelly, S.; Dietary nitrogen alters codon bias and genome composition in parasitic microorganisms; Genome Biology2016, 17, 1-15; https://doi.org/10.1186/s13059-016-0930-7
[27] Sen, P.; Kurmi, A.; Ray, S. K.; Satapathy, S. S.; Machine learning approach identifies prominent codons from different degenerate groups influencing gene expression in bacteria; Genes to Cells2022, 27(10), 591-601; https://doi.org/10.1111/gtc.12985
[28] Collins, D. W.; Jukes, T. H.; Rates of transition and transversion in coding sequences since the human-rodent divergence; Genomics1994, 20(3), 386-396; https://doi.org/10.1006/geno.1994.1188
[29] Beura, P. K.; Sen, P.; Aziz, R.; Satapathy, S. S.; Ray, S. K.; Transcribed intergenic regions exhibit a lower frequency of nucleotide polymorphism than the untranscribed intergenic regions in the genomes of Escherichia coli and Salmonella enterica; Journal of Genetics2023, 102(1), 22; https://doi.org/10.1007/s12041-023-01397-7
[30] Seplyarskiy, V. B.; Kharchenko, P.; Kondrashov, A. S.; Bazykin, G. A.; Heterogeneity of the transition/transversion ratio in Drosophila and Hominidae genomes; Molecular Biology and Evolution 2012, 29(8), 1943-1955; https://doi.org/10.1093/molbev/mss066
[31] Sen, P.; Aziz, R.; Deka, R. C.; Feil, E. J.; Ray, S. K.; Satapathy, S. S.; Stem region of tRNA genes favors transition substitution towards keto bases in bacteria; Journal of Molecular Evolution2022, 90(1), 114-123; https://doi.org/10.1007/s00239-022-10055-0.
[32] Osawa, S.; Jukes, T. H.; Codon reassignment (codon capture) in evolution; Journal of Molecular Evolution1989, 28(4), 271-278; https://doi.org/10.1007/BF02103414.
[33] Holmes, E. C.; Patterns of intra-and interhost nonsynonymous variation reveal strong purifying selection in dengue virus; Journal of Virology2003, 77(20), 11296-11298; https://doi.org/10.1128/JVI.77.20.11296-11298.2003.
[34] Nei, M.; Gojobori, T.; Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions; Molecular Biology and Evolution1986, 3(5), 418-426; https://doi.org/10.1093/oxfordjournals.molbev.a040410.
[35] Subramanian, S.; Significance of population size on the fixation of nonsynonymous mutations in genes under varying levels of selection pressure; Genetics2013, 193(3), 995-1002; https://doi.org/10.1534/genetics.112.147074.
[36] Teng, S.; Michonova-Alexova, E.; Alexov, E.; Approaches and resources for prediction of the effects of non-synonymous single nucleotide polymorphism on protein function and interactions; Current Pharmaceutical Biotechnology2008, 9(2), 123-133; https://doi.org/10.2174/138920108783955173.
[37] Gojobori, T.; Li, W. H.; Graur, D.; Patterns of nucleotide substitution in pseudogenes and functional genes; Journal of Molecular Evolution1982, 18(5), 360-369; https://doi.org/10.1007/BF02101694.
[38] Graur, D.; Li, W. H.; Molecular Evolution; Sinauer Associates: Sunderland, MA, USA, 2000.
[39] Wahl, M. C.; Sundaralingam, M.; Crystal structures of A‐DNA duplexes; Biopolymers: Original Research on Biomolecules1997, 44(1), 45-63
[40] Jukes, T. H.; Cantor, C. R.; Evolution of protein molecules; In Mammalian Protein Metabolism; Munro, H. N., Ed.; Academic Press: New York, NY, USA, 1969, Volume 3, 21-132. [No DOI available]
[41] Kimura, M.; A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences; Journal of Molecular Evolution1980, 16(2), 111-120; https://doi.org/10.1007/BF01731581.
[42] Muse, S. V.; Gaut, B. S.; A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to the chloroplast genome; Molecular Biology and Evolution1994, 11(5), 715-724; https://doi.org/10.1093/oxfordjournals.molbev.a040152.
[43] Griffiths, A. J. F.; An Introduction to Genetic Analysis, 7th ed.; W. H. Freeman: New York, NY, USA, 2000.
[44] Shendure, J.; Aiden, E. L.; The expanding scope of DNA sequencing; Nature Biotechnology2012, 30(11), 1084-1094; https://doi.org/10.1038/nbt.2421.
[45] Hershberg, R.; Mutation—the engine of evolution: studying mutation and its role in the evolution of bacteria; Cold Spring Harbor Perspectives in Biology2015, 7(9), a018077; https://doi.org/10.1101/cshperspect.a018077.
[46] Prehn, R. T.; The role of mutation in the new cancer paradigm; Cancer Cell International 2005, 5(1), 9; https://doi.org/10.1186/1475-2867-5-9.
[47] Sukhodolets, V. V.; The role of natural selection in evolution; Genetika1986, 22(2), 181-193.
[48] Gregory, T. R.; Understanding natural selection: Essential concepts and common misconceptions; Evolution: Education and Outreach2009, 2, 156-175; https://doi.org/10.1007/s12052-009-0114-3.
[49] Gulisija, D.; Crow, J. F.; Inferring purging from pedigree data; Evolution2007, 61(5), 1043-1051; https://doi.org/10.1111/j.1558-5646.2007.00088.x.
[50] Sarkar, S.; Haldane as biochemist: The Cambridge decade, 1923–1932; In The Founders of Evolutionary Genetics Boston Studies in the Philosophy of Science; Springer: Dordrecht, Netherlands, 1992; Volume 142, 53-81; https://doi.org/10.1007/978-94-011-2864-0_4.
[51] Nachman, M. W.; Haldane and the first estimates of the human mutation rate; Journal of Genetics2004, 83(3), 231-233; https://doi.org/10.1007/BF02717955.
[52] Kimura, M.; The Neutral Theory of Molecular Evolution Cambridge University Press: Cambridge, UK, 1983. [No DOI available]
[53] Hurst, L. D.; Genetics and the understanding of selection; Nature Reviews Genetics2009, 10, 83-93; https://doi.org/10.1038/nrg2506.
[54] Eyre-Walker, A.; Keightley, P. D.; The distribution of fitness effects of new mutations; Nature Reviews Genetics2007, 8(8), 610-618; https://doi.org/10.1038/nrg2146.
[55] Schmidt, S.; Gerasimova, A.; Kondrashov, F. A.; Adzhubei, I. A.; Kondrashov, A. S.; Sunyaev, S.; Hypermutable non-synonymous sites are under stronger negative selection; PLoS Genetics2008, 4(11), e1000281; https://doi.org/10.1371/journal.pgen.1000281.
[56] Rodrigue, N.; Philippe, H.; Lartillot, N.; Mutation-selection models of coding sequence evolution with site-heterogeneous amino acid fitness profiles; Proceedings of the National Academy of Sciences2010, 107(10), 4629-4634; https://doi.org/10.1073/pnas.0908092107.
[57] Shabalina, S. A.; Spiridonov, N. A.; Kashina, A.; Sounds of silence: Synonymous nucleotides as a key to biological regulation and complexity; Nucleic Acids Research2013, 41(4), 2073-2094; https://doi.org/10.1093/nar/gks1205.
[58] Liu, Y.; Yang, Q.; Zhao, F.; Synonymous but not silent: The codon usage code for gene expression and protein folding; Annual Review of Biochemistry2021, 90, 375-401; https://doi.org/10.1146/annurev-biochem-052820-105656.
[59] Elson, D.; Chargaff, E.; On the deoxyribonucleic acid content of sea urchin gametes; Experientia1952, 8(4), 143-145; https://doi.org/10.1007/BF02154632.
[60] Forsdyke, D. R.; Mortimer, J. R.; Chargaff's legacy; Gene2000, 261(1), 127-137; https://doi.org/10.1016/S0378-1119(00)00479-2.
[61] Lobry, J. R.; Properties of a general model of DNA evolution under no-strand-bias conditions; Journal of Molecular Evolution; 1995, 40(3), 326-330; https://doi.org/10.1007/BF00163239.
[62] Sueoka, N.; Intrastrand parity rules of DNA base composition and usage biases of synonymous codons; Journal of Molecular Evolution1995, 40(3), 318-325; https://doi.org/10.1007/BF00163238.
[63] Francino, M. P.; Ochman, H.; Strand asymmetries in DNA evolution; Trends in Genetics1997, 13(6), 240-245; https://doi.org/10.1016/S0168-9525(97)01119-4.
[64] Kornberg, A.; DNA replication; Trends in Biochemical Sciences; 1984, 9(4), 122-124; https://doi.org/10.1016/0968-0004(84)90110-5.
[65] Powdel, B. R.; Satapathy, S. S.; Kumar, A.; Jha, P. K.; Buragohain, A. K.; Borah, M.; Ray, S. K.; A study in entire chromosomes of violations of the intra-strand parity of complementary nucleotides (Chargaff's second parity rule); DNA Research2009, 16(6), 325-343; https://doi.org/10.1093/dnares/dsp019.
[66] Lindahl, T.; Nyberg, B.; Heat-induced deamination of cytosine residues in deoxyribonucleic acid; Biochemistry1974, 13(16), 3405-3410; https://doi.org/10.1021/bi00713a035.
[67] Lobry, J. R.; Sueoka, N.; Asymmetric directional mutation pressures in bacteria; Genome Biology; 2002, 3(10), 1-14; https://doi.org/10.1186/gb-2002-3-10-research0058.
[68] Kino, K.; Sugiyama, H.; Possible cause of G•C→C•G transversion mutation by guanine oxidation product, imidazolone; Chemistry & Biology2001, 8(4), 369-378; https://doi.org/10.1016/S1074-5521(01)00020-6.
[69] Bhagwat, A. S.; Hao, W.; Townes, J. P.; Lee, H.; Tang, H.; Foster, P. L.; Strand-biased cytosine deamination at the replication fork causes cytosine to thymine mutations in Escherichia coli; Proceedings of the National Academy of Sciences2016, 113(8), 2176-2181; https://doi.org/10.1073/pnas.1525329113.
[70] Francino, M. P.; Ochman, H.; Strand asymmetries in DNA evolution; Trends in Genetics1997, 13(6), 240-245; https://doi.org/10.1016/S0168-9525(97)01119-4.
[71] Mugal, C. F.; von Grünberg, H. H.; Peifer, M.; Transcription-induced mutational strand bias and its effect on substitution rates in human genes; Molecular Biology and Evolution2009, 26(1), 131-142; https://doi.org/10.1093/molbev/msn241.
[72] Zhao, X.; Zhang, Z.; Yan, J.; Yu, J.; GC content variability of eubacteria is governed by the pol III α subunit; Biochemical and Biophysical Research Communications2007, 356(1), 20-25; https://doi.org/10.1016/j.bbrc.2007.02.086.
[73] Muto, A.; Osawa, S.; The guanine and cytosine content of genomic DNA and bacterial evolution; Proceedings of the National Academy of Sciences1987, 84(1), 166-169; https://doi.org/10.1073/pnas.84.1.166.
[74] Brocchieri, L.; The GC content of bacterial genomes; Journal of Phylogenetics & Evolutionary Biology2014, 2, 1000133; https://doi.org/10.4172/2329-9002.1000133.
[75] Revell, L. J.; Mahler, D. L.; Peres-Neto, P. R.; Redelings, B. D.; A new phylogenetic method for identifying exceptional phenotypic diversification; Evolution2012, 66(1), 135-146; https://doi.org/10.1111/j.1558-5646.2011.01435.x.
[76] Brooks, S.; Markov chain Monte Carlo method and its application; Journal of the Royal Statistical Society: Series D (The Statistician)1998, 47(1), 69-100; https://doi.org/10.1111/1467-9884.00114.
[77] Heath, T. A.; Hedtke, S. M.; Hillis, D. M.; Taxon sampling and the accuracy of phylogenetic analyses; Journal of Systematics and Evolution2008, 46(3), 239-257; https://doi.org/10.3724/SP.J.1002.2008.08016.
[78] Hershberg, R.; Mutation the engine of evolution: Studying mutation and its role in the evolution of bacteria; Cold Spring Harbor Perspectives in Biology2015, 7(9), a018077; https://doi.org/10.1101/cshperspect.a018077.
[79] Mashima, J.; Kodama, Y.; Fujisawa, T.; Katayama, T.; Okuda, Y.; Kaminuma, E.; Takagi, T.; DNA data bank of Japan; Nucleic Acids Research2017, 45(D1), D25-D31; https://doi.org/10.1093/nar/gkw1001.
[80] NCBI Resource Coordinators; Database resources of the National Center for Biotechnology Information; Nucleic Acids Research2016, 44(D1), D7-D19; https://doi.org/10.1093/nar/gkv1290.
[81] Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., ... & Bourne, P. E.; The protein data bank; Nucleic acids research2000, 28(1), 235-242. https://doi.org/10.1093/nar/28.1.235
[82] Zardecki, C., Dutta, S., Goodsell, D. S., Lowe, R., Voigt, M., & Burley, S. K.; Educational resources supporting molecular explorations through biology and medicine. Protein Science2022, 31(1), 129-140. https://doi.org/10.1002/pro.4200
[83] The UniProt Consortium , UniProt: the Universal Protein Knowledgebase in 2025, Nucleic Acids Research, Volume 53, Issue D1, 6 January 2025, Pages D609–D617,. https://doi.org/10.1093/nar/gkae1010
[84] Benson, D. A.; Cavanaugh, M.; Clark, K.; Karsch-Mizrachi, I.; Ostell, J.; Pruitt, K. D.; Sayers, E. W.; GenBank. Nucleic Acids Research2018, 46(D1), D41–D47; https://doi.org/10.1093/nar/gkx1094
[85] Steane, D. A. et al.; Phylogenomic insights using IQ-TREE 2 and BEAST 2; Molecular Phylogenetics and Evolution2023, 184, 107781; https://doi.org/10.1016/j.ympev.2023.107781
[86] Kozlov, A. M. et al.; RAxML-NG: a fast, scalable and user-friendly tool for maximum likelihood phylogenetic inference; Bioinformatics2020, 36(5), 2672–2674; https://doi.org/10.1093/bioinformatics/btaa093
[87] Suchard, M. A. et al.; Bayesian phylogenetic and phylodynamic data integration using BEAST 2.6; Virus Evolution2020, 6(1), veaa042; https://doi.org/10.1093/ve/veaa042
[88] Kosakovsky Pond, S. L. et al.; HyPhy 2.5—A customizable platform for evolutionary hypothesis testing using phylogenies; Molecular Biology and Evolution2020, 37(1), 295–299; https://doi.org/10.1093/molbev/msz197
[89] Kumar, S.; Stecher, G., Suleski.; M., Sanderford.; M., Sharma, S.; & Tamura, K.; MEGA12: Molecular Evolutionary Genetic Analysis version 12 for adaptive and green computing. Molecular Biology and Evolution 2024, 41(12), msae263.https://doi.org/10.1093/molbev/msae263
[90] Yang, Z.; PAML 4: Phylogenetic analysis by maximum likelihood; Molecular Biology and Evolution; 2007, 24(8), 1586–1591; https://doi.org/10.1093/molbev/msm088
[91] R Core Team. R: A Language and Environment for Statistical Computing; R Foundation for Statistical Computing: Vienna, Austria, 2024; https://www.R-project.org/
[92] Langa, Ł. Python 3.9.13 is now available. Python Insider, 2022, May 17. Archived from the original on May 17, 2022. Retrieved May 21, 2022. Available at: https://blog.python.org/2022/05/python-3913-is-now-available.html
[93] Maeshiro, T.; Kimura, M.; The role of robustness and changeability on the origin and evolution of genetic codes; Proceedings of the National Academy of Sciences1998, 95(9), 5088-5093; https://doi.org/10.1073/pnas.95.9.5088.
[94] Franklin, I.; Lewontin, R. C.; Is the gene the unit of selection?; Genetics1970, 65(4), 707-734. [No DOI available]
[95] Sung, W.; Ackerman, M. S.; Gout, J. F.; Miller, S. F.; Williams, E.; Foster, P. L.; Lynch, M.; Asymmetric context-dependent mutation patterns revealed through mutation–accumulation experiments; Molecular Biology and Evolution2015, 32(7), 1672-1683; https://doi.org/10.1093/molbev/msv055.
[96] Zhu, Y.; Neeman, T.; Yap, V. B.; Huttley, G. A.; Statistical methods for identifying sequence motifs affecting point mutations; Genetics; 2017, 205(2), 843-856; https://doi.org/10.1534/genetics.116.193029.
[97] Beura, P. K..; A Study on Single Nucleotide Variations in Different Regions of Escherichia coli Genome Sequences, 2024,(Doctoral dissertation, Tezpur University).
Downloads
Abstract Display: 421 
PDF Downloads: 125 Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright © Author(s) retain the copyright of this article.
