{"id":"https://openalex.org/W4399979255","doi":"https://doi.org/10.3389/fbinf.2024.1381540","title":"The evolution of mammalian Rem2: unraveling the impact of purifying selection and coevolution on protein function, and implications for human disorders","display_name":"The evolution of mammalian Rem2: unraveling the impact of purifying selection and coevolution on protein function, and implications for human disorders","publication_year":2024,"publication_date":"2024-06-24","ids":{"openalex":"https://openalex.org/W4399979255","doi":"https://doi.org/10.3389/fbinf.2024.1381540","pmid":"https://pubmed.ncbi.nlm.nih.gov/38978817"},"language":"en","primary_location":{"id":"doi:10.3389/fbinf.2024.1381540","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fbinf.2024.1381540","pdf_url":"https://www.frontiersin.org/journals/bioinformatics/articles/10.3389/fbinf.2024.1381540/pdf","source":{"id":"https://openalex.org/S4210219554","display_name":"Frontiers in Bioinformatics","issn_l":"2673-7647","issn":["2673-7647"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Bioinformatics","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.frontiersin.org/journals/bioinformatics/articles/10.3389/fbinf.2024.1381540/pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5043759447","display_name":"Alexander G. Lucaci","orcid":"https://orcid.org/0000-0002-4896-6088"},"institutions":[{"id":"https://openalex.org/I4387153466","display_name":"Weill Cornell Medicine","ror":"https://ror.org/02r109517","country_code":"US","type":"education","lineage":["https://openalex.org/I205783295","https://openalex.org/I4387153466"]},{"id":"https://openalex.org/I205783295","display_name":"Cornell University","ror":"https://ror.org/05bnh6r87","country_code":"US","type":"education","lineage":["https://openalex.org/I205783295"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Alexander G. Lucaci","raw_affiliation_strings":["Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, United States","Weill Cornell Medicine, The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, United States"],"affiliations":[{"raw_affiliation_string":"Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, United States","institution_ids":["https://openalex.org/I205783295","https://openalex.org/I4387153466"]},{"raw_affiliation_string":"Weill Cornell Medicine, The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, United States","institution_ids":["https://openalex.org/I205783295","https://openalex.org/I4387153466"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5097249631","display_name":"William E. Brew","orcid":null},"institutions":[{"id":"https://openalex.org/I84392919","display_name":"Temple University","ror":"https://ror.org/00kx1jb78","country_code":"US","type":"education","lineage":["https://openalex.org/I84392919"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"William E. Brew","raw_affiliation_strings":["Department of Biology, Temple University, Philadelphia, PA, United States"],"affiliations":[{"raw_affiliation_string":"Department of Biology, Temple University, Philadelphia, PA, United States","institution_ids":["https://openalex.org/I84392919"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5076384273","display_name":"Jason J. Lamanna","orcid":"https://orcid.org/0000-0002-1357-6901"},"institutions":[{"id":"https://openalex.org/I84392919","display_name":"Temple University","ror":"https://ror.org/00kx1jb78","country_code":"US","type":"education","lineage":["https://openalex.org/I84392919"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jason Lamanna","raw_affiliation_strings":["Department of Biology, Temple University, Philadelphia, PA, United States","Institute for Computational Molecular Science, Temple University, Philadelphia, PA, United States"],"affiliations":[{"raw_affiliation_string":"Department of Biology, Temple University, Philadelphia, PA, United States","institution_ids":["https://openalex.org/I84392919"]},{"raw_affiliation_string":"Institute for Computational Molecular Science, Temple University, Philadelphia, PA, United States","institution_ids":["https://openalex.org/I84392919"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5034572150","display_name":"Avery Selberg","orcid":"https://orcid.org/0000-0002-6568-0583"},"institutions":[{"id":"https://openalex.org/I84392919","display_name":"Temple University","ror":"https://ror.org/00kx1jb78","country_code":"US","type":"education","lineage":["https://openalex.org/I84392919"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Avery Selberg","raw_affiliation_strings":["Department of Biology, Temple University, Philadelphia, PA, United States","Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA, United States"],"affiliations":[{"raw_affiliation_string":"Department of Biology, Temple University, Philadelphia, PA, United States","institution_ids":["https://openalex.org/I84392919"]},{"raw_affiliation_string":"Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA, United States","institution_ids":["https://openalex.org/I84392919"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5103020066","display_name":"Vincenzo Carnevale","orcid":"https://orcid.org/0000-0002-1918-8280"},"institutions":[{"id":"https://openalex.org/I84392919","display_name":"Temple University","ror":"https://ror.org/00kx1jb78","country_code":"US","type":"education","lineage":["https://openalex.org/I84392919"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Vincenzo Carnevale","raw_affiliation_strings":["Department of Biology, Temple University, Philadelphia, PA, United States","Institute for Computational Molecular Science, Temple University, Philadelphia, PA, United States"],"affiliations":[{"raw_affiliation_string":"Department of Biology, Temple University, Philadelphia, PA, United States","institution_ids":["https://openalex.org/I84392919"]},{"raw_affiliation_string":"Institute for Computational Molecular Science, Temple University, Philadelphia, PA, United States","institution_ids":["https://openalex.org/I84392919"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5071546456","display_name":"Anna R. Moore","orcid":"https://orcid.org/0000-0001-6183-906X"},"institutions":[{"id":"https://openalex.org/I84392919","display_name":"Temple University","ror":"https://ror.org/00kx1jb78","country_code":"US","type":"education","lineage":["https://openalex.org/I84392919"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Anna R. Moore","raw_affiliation_strings":["Department of Biology, Temple University, Philadelphia, PA, United States"],"affiliations":[{"raw_affiliation_string":"Department of Biology, Temple University, Philadelphia, PA, United States","institution_ids":["https://openalex.org/I84392919"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5011410563","display_name":"Sergei L. Kosakovsky Pond","orcid":"https://orcid.org/0000-0003-4817-4029"},"institutions":[{"id":"https://openalex.org/I84392919","display_name":"Temple University","ror":"https://ror.org/00kx1jb78","country_code":"US","type":"education","lineage":["https://openalex.org/I84392919"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Sergei L. Kosakovsky Pond","raw_affiliation_strings":["Department of Biology, Temple University, Philadelphia, PA, United States","Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA, United States"],"affiliations":[{"raw_affiliation_string":"Department of Biology, Temple University, Philadelphia, PA, United States","institution_ids":["https://openalex.org/I84392919"]},{"raw_affiliation_string":"Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA, United States","institution_ids":["https://openalex.org/I84392919"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":7,"corresponding_author_ids":["https://openalex.org/A5011410563","https://openalex.org/A5043759447"],"corresponding_institution_ids":["https://openalex.org/I205783295","https://openalex.org/I4387153466","https://openalex.org/I84392919"],"apc_list":{"value":1900,"currency":"USD","value_usd":1900},"apc_paid":{"value":1900,"currency":"USD","value_usd":1900},"fwci":0.2243,"has_fulltext":true,"cited_by_count":1,"citation_normalized_percentile":{"value":0.55318722,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":91,"max":95},"biblio":{"volume":"4","issue":null,"first_page":"1381540","last_page":"1381540"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10521","display_name":"RNA and protein synthesis mechanisms","score":0.9997000098228455,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10521","display_name":"RNA and protein synthesis mechanisms","score":0.9997000098228455,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10949","display_name":"Genetic Neurodegenerative Diseases","score":0.9980999827384949,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10301","display_name":"Mitochondrial Function and Pathology","score":0.996399998664856,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.8281146287918091},{"id":"https://openalex.org/keywords/gene","display_name":"Gene","score":0.580878734588623},{"id":"https://openalex.org/keywords/negative-selection","display_name":"Negative selection","score":0.5453913807868958},{"id":"https://openalex.org/keywords/genetics","display_name":"Genetics","score":0.5204294323921204},{"id":"https://openalex.org/keywords/coevolution","display_name":"Coevolution","score":0.4861835837364197},{"id":"https://openalex.org/keywords/evolutionary-biology","display_name":"Evolutionary biology","score":0.3883609175682068},{"id":"https://openalex.org/keywords/computational-biology","display_name":"Computational biology","score":0.3698301315307617},{"id":"https://openalex.org/keywords/genome","display_name":"Genome","score":0.19030454754829407}],"concepts":[{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.8281146287918091},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.580878734588623},{"id":"https://openalex.org/C7386963","wikidata":"https://www.wikidata.org/wiki/Q3954859","display_name":"Negative selection","level":4,"score":0.5453913807868958},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.5204294323921204},{"id":"https://openalex.org/C33009525","wikidata":"https://www.wikidata.org/wiki/Q208841","display_name":"Coevolution","level":2,"score":0.4861835837364197},{"id":"https://openalex.org/C78458016","wikidata":"https://www.wikidata.org/wiki/Q840400","display_name":"Evolutionary biology","level":1,"score":0.3883609175682068},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3698301315307617},{"id":"https://openalex.org/C141231307","wikidata":"https://www.wikidata.org/wiki/Q7020","display_name":"Genome","level":3,"score":0.19030454754829407}],"mesh":[],"locations_count":4,"locations":[{"id":"doi:10.3389/fbinf.2024.1381540","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fbinf.2024.1381540","pdf_url":"https://www.frontiersin.org/journals/bioinformatics/articles/10.3389/fbinf.2024.1381540/pdf","source":{"id":"https://openalex.org/S4210219554","display_name":"Frontiers in Bioinformatics","issn_l":"2673-7647","issn":["2673-7647"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Bioinformatics","raw_type":"journal-article"},{"id":"pmid:38978817","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/38978817","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in bioinformatics","raw_type":null},{"id":"pmh:oai:pubmedcentral.nih.gov:11228553","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11228553","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11228553/pdf/fbinf-04-1381540.pdf","source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Front Bioinform","raw_type":"Text"},{"id":"pmh:oai:doaj.org/article:1ddb041bf17341888a1691d77053b84d","is_oa":true,"landing_page_url":"https://doaj.org/article/1ddb041bf17341888a1691d77053b84d","pdf_url":null,"source":{"id":"https://openalex.org/S112646816","display_name":"SHILAP Revista de lepidopterolog\u00eda","issn_l":"0300-5267","issn":["0300-5267","2340-4078"],"is_oa":true,"is_in_doaj":true,"is_core":false,"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Frontiers in Bioinformatics, Vol 4 (2024)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.3389/fbinf.2024.1381540","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fbinf.2024.1381540","pdf_url":"https://www.frontiersin.org/journals/bioinformatics/articles/10.3389/fbinf.2024.1381540/pdf","source":{"id":"https://openalex.org/S4210219554","display_name":"Frontiers in Bioinformatics","issn_l":"2673-7647","issn":["2673-7647"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Bioinformatics","raw_type":"journal-article"},"sustainable_development_goals":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":false},"content_urls":{"pdf":"https://content.openalex.org/works/W4399979255.pdf"},"referenced_works_count":68,"referenced_works":["https://openalex.org/W1543942926","https://openalex.org/W1881807356","https://openalex.org/W1968371014","https://openalex.org/W1978107420","https://openalex.org/W1988209474","https://openalex.org/W1989110366","https://openalex.org/W1992485999","https://openalex.org/W1997914204","https://openalex.org/W2000761817","https://openalex.org/W2001466574","https://openalex.org/W2008397827","https://openalex.org/W2015572208","https://openalex.org/W2044044562","https://openalex.org/W2053599146","https://openalex.org/W2071484587","https://openalex.org/W2073737366","https://openalex.org/W2076617993","https://openalex.org/W2076806908","https://openalex.org/W2087962285","https://openalex.org/W2092119575","https://openalex.org/W2092888475","https://openalex.org/W2102245393","https://openalex.org/W2117681000","https://openalex.org/W2118982822","https://openalex.org/W2131203559","https://openalex.org/W2135509505","https://openalex.org/W2136847298","https://openalex.org/W2138533227","https://openalex.org/W2139695427","https://openalex.org/W2142377896","https://openalex.org/W2144775551","https://openalex.org/W2145429287","https://openalex.org/W2160378127","https://openalex.org/W2232479414","https://openalex.org/W2256016639","https://openalex.org/W2344050784","https://openalex.org/W2531904292","https://openalex.org/W2805904149","https://openalex.org/W2883315617","https://openalex.org/W2887044863","https://openalex.org/W2939703746","https://openalex.org/W2970147901","https://openalex.org/W3005235420","https://openalex.org/W3008085605","https://openalex.org/W3008295930","https://openalex.org/W3029661147","https://openalex.org/W3091933852","https://openalex.org/W3094188375","https://openalex.org/W3122109253","https://openalex.org/W3124450908","https://openalex.org/W3133659861","https://openalex.org/W3157508175","https://openalex.org/W3162509249","https://openalex.org/W3177828909","https://openalex.org/W4200447364","https://openalex.org/W4210644165","https://openalex.org/W4210871949","https://openalex.org/W4238944581","https://openalex.org/W4243391877","https://openalex.org/W4249248728","https://openalex.org/W4281653840","https://openalex.org/W4281790889","https://openalex.org/W4283263493","https://openalex.org/W4317634074","https://openalex.org/W4321789549","https://openalex.org/W4366482837","https://openalex.org/W4379533981","https://openalex.org/W4382919415"],"related_works":["https://openalex.org/W3144412313","https://openalex.org/W2634235285","https://openalex.org/W2492504662","https://openalex.org/W2142431990","https://openalex.org/W1597399711","https://openalex.org/W2139846551","https://openalex.org/W2125107234","https://openalex.org/W2171695241","https://openalex.org/W2964733764","https://openalex.org/W2159595936"],"abstract_inverted_index":{"Rad":[0],"And":[1],"Gem-Like":[2],"GTP-Binding":[3],"Protein":[4],"2":[5],"(Rem2),":[6],"a":[7,204],"member":[8],"of":[9,13,40,51,66,81,88,107,119,125,143,150,159,167,198,207],"the":[10,30,37,49,105,139,157,164,183,194,199],"RGK":[11],"family":[12],"Ras-like":[14],"GTPases,":[15],"is":[16,26,86,99],"implicated":[17],"in":[18,29,43,56,79,95,104,116,122,173],"Huntington's":[19],"disease":[20],"and":[21,25,32,54,60,98,110,152,187,196,210],"Long":[22],"QT":[23],"Syndrome":[24],"highly":[27],"expressed":[28],"brain":[31],"endocrine":[33],"cells.":[34],"We":[35,112],"examine":[36],"evolutionary":[38,141],"history":[39,142],"Rem2":[41,67,145,168,200],"identified":[42],"various":[44],"mammalian":[45,71,144],"species,":[46],"focusing":[47],"on":[48,133],"role":[50,103],"purifying":[52,77],"selection":[53,78],"coevolution":[55],"shaping":[57],"its":[58,208],"sequence":[59,166,195],"protein":[61,147,171],"structural":[62],"constraints.":[63,212],"Our":[64],"analysis":[65],"sequences":[68,154],"across":[69],"175":[70],"species":[72],"found":[73],"evidence":[74],"for":[75],"strong":[76],"70%":[80],"non-invariant":[82],"codon":[83,120],"sites":[84,121],"which":[85,126,155],"characteristic":[87],"essential":[89],"proteins":[90],"that":[91,162,191],"play":[92],"critical":[93],"roles":[94],"biological":[96,209],"processes":[97],"consistent":[100],"with":[101],"Rem2's":[102],"regulation":[106],"neuronal":[108],"development":[109],"function.":[111],"inferred":[113],"epistatic":[114],"effects":[115,132],"50":[117],"pairs":[118],"Rem2,":[123],"some":[124],"are":[127],"predicted":[128],"to":[129],"have":[130,192],"deleterious":[131],"human":[134],"health.":[135],"Additionally,":[136],"we":[137,202],"reconstructed":[138],"ancestral":[140],"using":[146],"structure":[148,172,197],"prediction":[149],"extinct":[151],"extant":[153],"revealed":[156],"dynamics":[158],"how":[160],"substitutions":[161],"change":[163],"gene":[165,188],"can":[169],"impact":[170],"variable":[174],"regions":[175],"while":[176],"maintaining":[177],"core":[178],"functional":[179,211],"mechanisms.":[180],"By":[181],"understanding":[182,206],"selective":[184],"pressures,":[185],"protein-":[186],"-":[189],"interactions":[190],"shaped":[193],"protein,":[201],"gain":[203],"stronger":[205]},"counts_by_year":[{"year":2025,"cited_by_count":1}],"updated_date":"2026-04-21T08:09:41.155169","created_date":"2025-10-10T00:00:00"}