{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:07:30Z","timestamp":1760242050583,"version":"build-2065373602"},"reference-count":66,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T00:00:00Z","timestamp":1544572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The family of Chlamydiaceae contains a group of obligate intracellular bacteria that can infect a wide range of hosts. The evolutionary trend of members in this family is a hot topic, which benefits our understanding of the cross-infection of these pathogens. In this study, 14 whole genomes of 12 Chlamydia species were used to investigate the nucleotide, codon, and amino acid usage bias by synonymous codon usage value and information entropy method. The results showed that all the studied Chlamydia spp. had A\/T rich genes with over-represented A or T at the third positions and G or C under-represented at these positions, suggesting that nucleotide usages influenced synonymous codon usages. The overall codon usage trend from synonymous codon usage variations divides the Chlamydia spp. into four separate clusters, while amino acid usage divides the Chlamydia spp. into two clusters with some exceptions, which reflected the genetic diversity of the Chlamydiaceae family members. The overall codon usage pattern represented by the effective number of codons (ENC) was significantly positively correlated to gene GC3 content. A negative correlation exists between ENC and the codon adaptation index for some Chlamydia species. These results suggested that mutation pressure caused by nucleotide composition constraint played an important role in shaping synonymous codon usage patterns. Furthermore, codon usage of T3ss and Pmps gene families adapted to that of the corresponding genome. Taken together, analyses help our understanding of evolutionary interactions between nucleotide, synonymous codon, and amino acid usages in genes of Chlamydiaceae family members.<\/jats:p>","DOI":"10.3390\/ijms19124010","type":"journal-article","created":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T10:54:26Z","timestamp":1544612066000},"page":"4010","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synonymous Codon Usages as an Evolutionary Dynamic for Chlamydiaceae"],"prefix":"10.3390","volume":"19","author":[{"given":"Zhaocai","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China"},{"name":"Gansu Police Vocational College, Lanzhou 730046, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoan","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China"},{"name":"Biomedical Research Center, Northwest Minzu University, Lanzhou 730030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youjun","family":"Shang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jizhang","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.meegid.2014.01.029","article-title":"Evolution, phylogeny, and molecular epidemiology of Chlamydia","volume":"23","author":"Nunes","year":"2014","journal-title":"Infect. Genet. Evolut."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.syapm.2014.12.004","article-title":"Emendation of the family Chlamydiaceae: Proposal of a single genus, Chlamydia, to include all currently recognized species","volume":"38","author":"Sachse","year":"2015","journal-title":"Syst. Appl. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Vorimore, F., Hsia, R.C., Huot-Creasy, H., Bastian, S., Deruyter, L., Passet, A., Sachse, K., Bavoil, P., Myers, G., and Laroucau, K. (2013). Isolation of a New Chlamydia species from the Feral Sacred Ibis (Threskiornis aethiopicus): Chlamydia ibidis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074823"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.vetmic.2009.03.014","article-title":"Zoonotic potential of Chlamydophila","volume":"140","author":"Rodolakis","year":"2010","journal-title":"Vet. Microbiol."},{"key":"ref_5","first-page":"207","article-title":"Survey, Culture, and Genome Analysis of Ocular Chlamydia trachomatis in Tibetan Boarding Primary Schools in Qinghai Province, China","volume":"6","author":"Feng","year":"2016","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ajog.2016.08.008","article-title":"Sexually transmitted diseases and infertility","volume":"216","author":"Tsevat","year":"2017","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5327","DOI":"10.1128\/IAI.02576-14","article-title":"Plasmid-encoded Pgp3 is a major virulence factor for Chlamydia muridarum to induce hydrosalpinx in mice","volume":"82","author":"Liu","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1128\/CMR.8.4.451","article-title":"Chlamydia pneumoniae (TWAR)","volume":"8","author":"Kuo","year":"1995","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.vetmic.2008.09.046","article-title":"Chlamydophila psittaci infections in birds: A review with emphasis on zoonotic consequences","volume":"135","author":"Harkinezhad","year":"2009","journal-title":"Vet Microbiol."},{"key":"ref_10","first-page":"658519","article-title":"Identification and characterization of Chlamydia abortus isolates from yaks in Qinghai, China","volume":"2015","author":"Li","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0378-1135(00)00213-3","article-title":"Chlamydia and Chlamydiales: More than meets the eye","volume":"75","author":"Everett","year":"2000","journal-title":"Vet Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1111\/j.1462-2920.2012.02800.x","article-title":"Molecular characterization of atypical Chlamydia and evidence of their dissemination in different European and Asian chicken flocks by specific real-time PCR","volume":"14","author":"Zocevic","year":"2012","journal-title":"Environ. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zocevic, A., Vorimore, F., Vicari, N., Gasparini, J., Jacquin, L., Sachse, K., Magnino, S., and Laroucau, K. (2013). A real-time PCR assay for the detection of atypical strains of Chlamydiaceae from pigeons. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058741"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.femsre.2005.03.002","article-title":"The chlamydial developmental cycle","volume":"29","author":"Abdelrahman","year":"2005","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1111\/j.1365-2958.2010.07386.x","article-title":"Members of the Pmp protein family of Chlamydia pneumoniae mediate adhesion to human cells via short repetitive peptide motifs","volume":"78","author":"Molleken","year":"2010","journal-title":"Mol. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1128\/JB.188.1.275-286.2006","article-title":"Polymorphisms in the nine polymorphic membrane proteins of Chlamydia trachomatis across all serovars: Evidence for serovar Da recombination and correlation with tissue tropism","volume":"188","author":"Gomes","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5473","DOI":"10.1128\/IAI.68.10.5473-5479.2000","article-title":"Genome sequencing and our understanding of chlamydiae","volume":"68","author":"Rockey","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1128\/IAI.00917-13","article-title":"New frontiers in type III secretion biology: The Chlamydia perspective","volume":"82","author":"Mueller","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.micinf.2015.10.006","article-title":"A working model for the type III secretion mechanism in Chlamydia","volume":"18","author":"Ferrell","year":"2016","journal-title":"Microb. Infect."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1128\/MMBR.62.2.379-433.1998","article-title":"Type III protein secretion systems in bacterial pathogens of animals and plants","volume":"62","author":"Hueck","year":"1998","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.mib.2008.11.009","article-title":"Effector protein modulation of host cells: Examples in the Chlamydia spp. arsenal","volume":"12","author":"Betts","year":"2009","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1016\/j.celrep.2017.04.058","article-title":"Absence of Specific Chlamydia trachomatis Inclusion Membrane Proteins Triggers Premature Inclusion Membrane Lysis and Host Cell Death","volume":"19","author":"Weber","year":"2017","journal-title":"Cell Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1128\/IAI.03140-14","article-title":"Comparative genome sequencing of Rickettsia rickettsii strains that differ in virulence","volume":"83","author":"Clark","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1126\/science.282.5389.754","article-title":"Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis","volume":"282","author":"Stephens","year":"1998","journal-title":"Science (New York, N.Y.)"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/nrmicro.2016.30","article-title":"Chlamydia cell biology and pathogenesis","volume":"14","author":"Elwell","year":"2016","journal-title":"Nature Rev. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1101\/gr.200931.115","article-title":"A novel nuclear genetic code alteration in yeasts and the evolution of codon reassignment in eukaryotes","volume":"26","author":"Muhlhausen","year":"2016","journal-title":"Genome Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/nrmicro3568","article-title":"Genetic code flexibility in microorganisms: Novel mechanisms and impact on physiology","volume":"13","author":"Ling","year":"2015","journal-title":"Nature Rev. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1093\/dnares\/dsv027","article-title":"New insights into the interplay between codon bias determinants in plants","volume":"22","author":"Camiolo","year":"2015","journal-title":"DNA Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1098\/rstb.2009.0305","article-title":"Forces that influence the evolution of codon bias","volume":"365","author":"Sharp","year":"2010","journal-title":"Phil. Trans. R. Soc. Lond. B"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s12304-010-9087-8","article-title":"Towards an Evolutionary Biosemiotics: Semiotic Selection and Semiotic Co-option","volume":"3","author":"Maran","year":"2010","journal-title":"Biosemiotics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1002\/jobm.201700652","article-title":"Adaptation of Borrelia burgdorferi to its natural hosts by synonymous codon and amino acid usage","volume":"58","author":"Ma","year":"2018","journal-title":"J. Basic Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biosystems.2017.12.008","article-title":"Unique features of nucleotide and codon usage patterns in mycoplasmas revealed by information entropy","volume":"165","author":"Wang","year":"2018","journal-title":"Biosystems"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.gene.2017.09.045","article-title":"Analyses of nucleotide, codon and amino acids usages between peste des petits ruminants virus and rinderpest virus","volume":"637","author":"Ma","year":"2017","journal-title":"Gene"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mioduser, O., Goz, E., and Tuller, T. (2017). Significant differences in terms of codon usage bias between bacteriophage early and late genes: A comparative genomics analysis. BMC Genom., 18.","DOI":"10.1186\/s12864-017-4248-7"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"770","DOI":"10.15252\/msb.20145524","article-title":"Causal signals between codon bias, mRNA structure, and the efficiency of translation and elongation","volume":"10","author":"Pop","year":"2014","journal-title":"Mol. Syst. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.molcel.2015.07.018","article-title":"Codon Usage Influences the Local Rate of Translation Elongation to Regulate Co-translational Protein Folding","volume":"59","author":"Yu","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1073\/pnas.95.7.3720","article-title":"Strand compositional asymmetry in bacterial and large viral genomes","volume":"95","author":"Mrazek","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Guo, F.B., and Yu, X.J. (2007). Separate base usages of genes located on the leading and lagging strands in Chlamydia muridarum revealed by the Z curve method. BMC Genom., 8.","DOI":"10.1186\/1471-2164-8-366"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.gene.2005.10.035","article-title":"Synonymous codon usage in environmental chlamydia UWE25 reflects an evolutional divergence from pathogenic chlamydiae","volume":"368","author":"Zhou","year":"2006","journal-title":"Gene"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.gene.2018.03.065","article-title":"The analyses of relationships among nucleotide, synonymous codon and amino acid usages for E2 gene of bovine viral diarrhea virus","volume":"660","author":"Ma","year":"2018","journal-title":"Gene"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1002\/jobm.201700490","article-title":"Comparative genomic analysis for nucleotide, codon, and amino acid usage patterns of mycoplasmas","volume":"58","author":"Ma","year":"2018","journal-title":"J. Basic Microbiol."},{"key":"ref_42","first-page":"91","article-title":"Synonymous codon usage in bacteria","volume":"3","author":"Ermolaeva","year":"2001","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Nasrullah, I., Butt, A.M., Tahir, S., Idrees, M., and Tong, Y. (2015). Genomic analysis of codon usage shows influence of mutation pressure, natural selection, and host features on Marburg virus evolution. BMC Evolut. Biol., 15.","DOI":"10.1186\/s12862-015-0456-4"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e107","DOI":"10.1038\/emi.2016.106","article-title":"Evolution of codon usage in Zika virus genomes is host and vector specific","volume":"5","author":"Butt","year":"2016","journal-title":"Emerg. Microbes. Infect."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1093\/molbev\/msl097","article-title":"The evolution of biased codon and amino acid usage in nematode genomes","volume":"23","author":"Cutter","year":"2006","journal-title":"Mol. Biol. Evolut."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2870","DOI":"10.1128\/IAI.00106-15","article-title":"Mutational Analysis of the Chlamydia muridarum Plasticity Zone","volume":"83","author":"Rajaram","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_47","first-page":"11334","article-title":"Energy efficiency trade-offs drive nucleotide usage in transcribed regions","volume":"7","author":"Chen","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1534\/genetics.109.101782","article-title":"Estimating selection intensity on synonymous codon usage in a nonequilibrium population","volume":"183","author":"Zeng","year":"2009","journal-title":"Genetics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2480","DOI":"10.1111\/j.1365-294X.2012.05529.x","article-title":"Protein elemental sparing and codon usage bias are correlated among bacteria","volume":"21","author":"Bragg","year":"2012","journal-title":"Mol. Ecol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Buckland, R.J., Watt, D.L., Chittoor, B., Nilsson, A.K., Kunkel, T.A., and Chabes, A. (2014). Increased and imbalanced dNTP pools symmetrically promote both leading and lagging strand replication infidelity. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004846"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1186\/s13059-016-1087-9","article-title":"Dietary nitrogen alters codon bias and genome composition in parasitic microorganisms","volume":"17","author":"Seward","year":"2016","journal-title":"Genome Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.tig.2003.12.009","article-title":"Driving change: The evolution of alternative genetic codes","volume":"20","author":"Santos","year":"2004","journal-title":"Trends Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1073\/pnas.88.3.921","article-title":"CGG: An unassigned or nonsense codon in Mycoplasma capricolum","volume":"88","author":"Oba","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/BF02103422","article-title":"Codon reassignment (codon capture) in evolution","volume":"28","author":"Osawa","year":"1989","journal-title":"J. Mol. Evolut."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.meegid.2018.08.004","article-title":"Analyses of nucleotide, synonymous codon and amino acid usages at gene levels of Brucella melitensis strain QY1","volume":"65","author":"Cao","year":"2018","journal-title":"Infect. Genet. Evolut."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1159\/000495172","article-title":"Type III Interferons in Viral Infection and Antiviral Immunity","volume":"51","author":"Zhou","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tim.2014.04.013","article-title":"Chlamydia genomics: Providing novel insights into chlamydial biology","volume":"22","author":"Bachmann","year":"2014","journal-title":"Trends Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kim, H., Kwak, W., Yoon, S.H., Kang, D.K., and Kim, H. (2018). Horizontal gene transfer of Chlamydia: Novel insights from tree reconciliation. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0195139"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Jewett, T.J., Miller, N.J., Dooley, C.A., and Hackstadt, T. (2010). The conserved Tarp actin binding domain is important for chlamydial invasion. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000997"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"362104","DOI":"10.1155\/2012\/362104","article-title":"Evolution and conservation of predicted inclusion membrane proteins in chlamydiae","volume":"2012","author":"Lutter","year":"2012","journal-title":"Comp. Funct. Genom."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.gene.2009.04.022","article-title":"Analyzing gene expression from relative codon usage bias in Yeast genome: A statistical significance and biological relevance","volume":"443","author":"Das","year":"2009","journal-title":"Gene"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0168-9525(02)02690-2","article-title":"Base composition bias might result from competition for metabolic resources","volume":"18","author":"Rocha","year":"2002","journal-title":"Trends Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"7737","DOI":"10.1093\/nar\/14.19.7737","article-title":"Codon usage in regulatory genes in Escherichia coli does not reflect selection for \u2018rare\u2019 codons","volume":"14","author":"Sharp","year":"1986","journal-title":"Nucleic Acids Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.meegid.2012.09.020","article-title":"The analysis of codon bias of foot-and-mouth disease virus and the adaptation of this virus to the hosts","volume":"14","author":"Zhou","year":"2013","journal-title":"Infect. Genet. Evolut."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0378-1119(90)90491-9","article-title":"The \u2018effective number of codons\u2019 used in a gene","volume":"87","author":"Wright","year":"1990","journal-title":"Gene"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Zhou, J.H., Zhang, J., Sun, D.J., Ma, Q., Chen, H.T., Ma, L.N., Ding, Y.Z., and Liu, Y.S. (2013). The distribution of synonymous codon choice in the translation initiation region of dengue virus. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077239"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/12\/4010\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:33:31Z","timestamp":1760196811000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/12\/4010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,12]]},"references-count":66,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["ijms19124010"],"URL":"https:\/\/doi.org\/10.3390\/ijms19124010","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2018,12,12]]}}}