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Insertions and deletions make up to 25% of genomic variants in humans and are involved in complex evolutionary processes including genomic rearrangements, adaptation, and speciation. Recent advances in long-read sequencing technologies allow detailed inference of insertions and deletion variation in species and populations. Yet, despite their importance, evolutionary studies have traditionally ignored or mishandled insertions and deletions due to a lack of comprehensive methodologies and statistical models of insertions and deletion dynamics. Here, we discuss methods for describing insertions and deletion variation and modeling insertions and deletions over evolutionary time. We provide practical advice for tackling insertions and deletions in genomic sequences and illustrate our discussion with examples of insertions and deletion-induced effects in human and other natural populations and their contribution to evolutionary processes. We outline promising directions for future developments in statistical methodologies that would allow researchers to analyze insertions and deletion variation and their effects in large genomic data sets and to incorporate insertions and deletions in evolutionary inference.<\/jats:p>","DOI":"10.1093\/molbev\/msae177","type":"journal-article","created":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T04:18:12Z","timestamp":1724386692000},"source":"Crossref","is-referenced-by-count":37,"title":["Insertions and Deletions: Computational Methods, Evolutionary Dynamics, and Biological Applications"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3278-4343","authenticated-orcid":false,"given":"Benjamin D","family":"Redelings","sequence":"first","affiliation":[{"name":"Department of Mathematics, Tulane University , New Orleans, LA 70118 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7639-5369","authenticated-orcid":false,"given":"Ian","family":"Holmes","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of California , Berkeley, CA 94720 ,","place":["USA"]},{"name":"Calico Life Sciences LLC , South San Francisco, CA 94080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3798-2058","authenticated-orcid":false,"given":"Gerton","family":"Lunter","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University Medical Center Groningen, University of Groningen , Groningen 9713 GZ ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9463-2575","authenticated-orcid":false,"given":"Tal","family":"Pupko","sequence":"additional","affiliation":[{"name":"The Shmunis School of Biomedicine and Cancer Research, George S. 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