{"doi":"10.7287/peerj.preprints.806v1","title":"The shiftability of protein coding genes: the genetic code was optimized for frameshift tolerating","abstract":"<jats:p>\n                  The genetic code defines the relationship between a protein and its coding DNA sequence. It was presumed that most frameshifts would yield non-functional, truncated or cytotoxic products. In this study, we report that in\n                  <jats:italic>E. coli</jats:italic>\n                  , a frameshift β-lactamase (bla) gene is still functional if all of the inner stop codons were readthrough or replaced by a sense codon. By analyzing a large dataset including all available protein coding genes in major model organisms, it is demonstrated that in any species, and in any protein-coding genes, the three translational products from the three different reading frames, are always similar to each other and with constant ~50% similarities and ~100% coverages, and the similarities is predefined by the genetic code rather than the sequences themselves. It is likely that a coding gene can be translated into three isoforms from each of the three reading frames, we propose a new gene expression paradigm, “\n                  <jats:italic>one transcript, three translations</jats:italic>\n                  ”, which is an amendment to the traditional “\n                  <jats:italic>one gene, one/multiple peptides</jats:italic>\n                  ” hypotheses. Finally, we concluded that the genetic code was optimized for frameshift tolerating in the early evolution, which endows every protein coding gene a character of\n                  <jats:italic>shiftability</jats:italic>\n                  , an inherent and everlasting ability to tolerate frameshift mutations, and serves as an innate mechanism for cells to deal with the frameshift problem.\n                </jats:p>","journal":null,"year":null,"id":34081,"datarank":0.565412161507612,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.18066975788838135,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.18066975788838135,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":10,"citers_with_citation_signal":9,"citers_with_endowment":9,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":177123,"name":"Xuxiang Wang","orcid":null,"position":1,"is_corresponding":false},{"id":105505,"name":"Gang Chen","orcid":null,"position":2,"is_corresponding":false},{"id":177124,"name":"Jianye Zhang","orcid":null,"position":3,"is_corresponding":false},{"id":177125,"name":"Yongqiang Liu","orcid":null,"position":4,"is_corresponding":false},{"id":42720,"name":"Chao Yang","orcid":"0000-0001-7909-1707","position":5,"is_corresponding":false},{"id":84458,"name":"Xiaolong Wang","orcid":"0000-0002-5061-2529","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18998881","pmcid":null,"openalex_id":"https://openalex.org/W2099973031","authors":[],"funders":[],"total_grants":0,"fwci":0.6024,"citation_percentile":0.69219854,"influential_citations":1,"citation_trend":[{"year":2016,"count":1},{"year":2017,"count":1},{"year":2018,"count":2},{"year":2019,"count":3},{"year":2020,"count":3},{"year":2022,"count":1},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.7287/peerj.preprints.806v1","host_type":""},{"url":"https://doi.org/10.7287/peerj.preprints.806v1","host_type":"GREEN"},{"url":"https://doi.org/10.7287/peerj.preprints.806v1","host_type":""},{"url":"https://peerj.com/preprints/806v1.pdf","host_type":"publisher"},{"url":"https://peerj.com/preprints/806v1.xml","host_type":"publisher"},{"url":"https://peerj.com/preprints/806v1.html","host_type":"publisher"}],"fields_of_study":["RNA and protein synthesis mechanisms","Bacterial Genetics and Biotechnology","Genomics and Phylogenetic Studies","Biology"],"mesh_terms":[],"keywords":["Frameshift mutation","Gene","Reading frame","Genetic code","Open reading frame","Coding region","Genetics","Stop codon","Biology","Codon usage bias","Computational biology","Mutation","Genome","Peptide sequence"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Quality Education"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-09T17:36:16.009800Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}