{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:33:45Z","timestamp":1784543625452,"version":"3.55.0"},"reference-count":118,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T00:00:00Z","timestamp":1611273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Spanish Ministry of Economy and Competitiveness","award":["RYC-2015-18241"],"award-info":[{"award-number":["RYC-2015-18241"]}]},{"name":"Spanish Ministry of Economy and Competitiveness","award":["IJCI-2016-29550"],"award-info":[{"award-number":["IJCI-2016-29550"]}]},{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["ED431F 2018\/08"],"award-info":[{"award-number":["ED431F 2018\/08"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/143607\/2019"],"award-info":[{"award-number":["SFRH\/BD\/143607\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The evolution of protein-coding genes is usually driven by selective processes, which favor some evolutionary trajectories over others, optimizing the subsequent protein stability and activity. The analysis of selection in this type of genetic data is broadly performed with the metric nonsynonymous\/synonymous substitution rate ratio (dN\/dS). However, most of the well-established methodologies to estimate this metric make crucial assumptions, such as lack of recombination or invariable codon frequencies along genes, which can bias the estimation. Here, we review the most relevant biases in the dN\/dS estimation and provide a detailed guide to estimate this metric using state-of-the-art procedures that account for such biases, along with illustrative practical examples and recommendations. We also discuss the traditional interpretation of the estimated dN\/dS emphasizing the importance of considering complementary biological information such as the role of the observed substitutions on the stability and function of proteins. This review is oriented to help evolutionary biologists that aim to accurately estimate selection in protein-coding sequences.<\/jats:p>","DOI":"10.1093\/bib\/bbaa431","type":"journal-article","created":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T12:33:05Z","timestamp":1608726785000},"source":"Crossref","is-referenced-by-count":31,"title":["Analysis of selection in protein-coding sequences accounting for common biases"],"prefix":"10.1093","volume":"22","author":[{"given":"Roberto","family":"Del Amparo","sequence":"first","affiliation":[{"name":"CINBIO (Biomedical Research Center), University of Vigo, 36310 Vigo, Spain"},{"name":"Department of Biochemistry, Genetics and Immunology, University of Vigo, 36310 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Branco","sequence":"additional","affiliation":[{"name":"CINBIO (Biomedical Research Center), University of Vigo, 36310 Vigo, Spain"},{"name":"Department of Biochemistry, Genetics and Immunology, University of Vigo, 36310 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Arenas","sequence":"additional","affiliation":[{"name":"Unit of Microbiology and Immunology, University of Zaragoza, 50013 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Vicens","sequence":"additional","affiliation":[{"name":"CINBIO (Biomedical Research Center), University of Vigo, 36310 Vigo, Spain"},{"name":"Department of Biochemistry, Genetics and Immunology, University of Vigo, 36310 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0516-2717","authenticated-orcid":false,"given":"Miguel","family":"Arenas","sequence":"additional","affiliation":[{"name":"CINBIO (Biomedical Research Center), University of Vigo, 36310 Vigo, Spain"},{"name":"Department of Biochemistry, Genetics and Immunology, University of Vigo, 36310 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,1,22]]},"reference":[{"issue":"2","key":"2021090812524268100_ref1","first-page":"150","article-title":"A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes","volume":"2","author":"Li","year":"1985","journal-title":"Mol Biol Evol"},{"issue":"5","key":"2021090812524268100_ref2","first-page":"715","article-title":"A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to the chloroplast genome","volume":"11","author":"Muse","year":"1994","journal-title":"Mol Biol Evol"},{"issue":"5","key":"2021090812524268100_ref3","first-page":"725","article-title":"A codon-based model of nucleotide substitution for protein-coding DNA sequences","volume":"11","author":"Goldman","year":"1994","journal-title":"Mol Biol 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