{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:53:19Z","timestamp":1791582799734,"version":"4.3.4"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Large-scale comparative genomics studies offer valuable resources for understanding both functional and evolutionary rate constraints. It is suggested that constraint aligns with the topology of genomic networks, increasing toward the center, with intermediate nodes combining relaxed constraint with higher contributions to the phenotype due to pleiotropy. However, this pattern has yet to be demonstrated in vertebrates. This study shows that constraint intensifies toward the network's center in placental mammals. Genes with rate changes associated with emergence of hibernation cluster mostly toward intermediate positions, with higher constraint in faster-evolving genes, which is indicative of a \u201csweet spot\u201d for adaptation. If this trend holds universally, network node metrics could predict high-constraint regions even in clades lacking empirical constraint data.<\/jats:p>","DOI":"10.1093\/molbev\/msae033","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T06:56:19Z","timestamp":1707980179000},"source":"Crossref","is-referenced-by-count":5,"title":["Brief Communication: The Predictable Network Topology of Evolutionary Genomic Constraint"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8858-1804","authenticated-orcid":false,"given":"Katharina C","family":"Wollenberg Valero","sequence":"first","affiliation":[{"name":"School of Biology and Environmental Science, University College Dublin , Belfield , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,16]]},"reference":[{"issue":"7993","key":"2024032920255669400_msae033-B1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41586-023-06045-0","article-title":"A genomic mutational constraint map using variation in 76,156 human genomes","volume":"625","author":"Chen","year":"2023","journal-title":"Nature"},{"issue":"6643","key":"2024032920255669400_msae033-B2","doi-asserted-by":"crossref","first-page":"eabn3943","DOI":"10.1126\/science.abn3943","article-title":"Evolutionary constraint and innovation across hundreds of placental mammals","volume":"380","author":"Christmas","year":"2023","journal-title":"Science"},{"issue":"5","key":"2024032920255669400_msae033-B3","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1093\/sysbio\/sys004","article-title":"Ultraconserved elements anchor thousands of genetic markers spanning multiple evolutionary timescales","volume":"61","author":"Faircloth","year":"2012","journal-title":"Syst Biol."},{"issue":"7833","key":"2024032920255669400_msae033-B4","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/s41586-020-2873-9","article-title":"Dense sampling of bird diversity increases power of comparative genomics","volume":"587","author":"Feng","year":"2020","journal-title":"Nature"},{"issue":"6","key":"2024032920255669400_msae033-B5","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/j.cell.2012.04.028","article-title":"Functional repurposing revealed by comparing S. pombe and S. cerevisiae genetic interactions","volume":"149","author":"Frost","year":"2012","journal-title":"Cell"},{"issue":"7","key":"2024032920255669400_msae033-B6","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1111\/j.1558-5646.2010.00960.x","article-title":"Evolutionary constraint and ecological consequences","volume":"64","author":"Futuyma","year":"2010","journal-title":"Evolution"},{"issue":"1","key":"2024032920255669400_msae033-B7","doi-asserted-by":"crossref","first-page":"4077","DOI":"10.1038\/s41467-019-11943-x","article-title":"Environmental temperatures shape thermal physiology as well as diversification and genome-wide substitution rates in lizards","volume":"10","author":"Garcia-Porta","year":"2019","journal-title":"Nat Commun"},{"issue":"4","key":"2024032920255669400_msae033-B8","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1534\/genetics.106.060269","article-title":"Toward a molecular understanding of pleiotropy","volume":"173","author":"He","year":"2006","journal-title":"Genetics"},{"issue":"1","key":"2024032920255669400_msae033-B9","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/bib\/bbq072","article-title":"PHAST and RPHAST: phylogenetic analysis with space\/time models","volume":"12","author":"Hubisz","year":"2011","journal-title":"Brief Bioinform"},{"issue":"5840","key":"2024032920255669400_msae033-B10","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1126\/science.1142430","article-title":"Human genome ultraconserved elements are ultraselected","volume":"317","author":"Katzman","year":"2007","journal-title":"Science"},{"issue":"1","key":"2024032920255669400_msae033-B11","doi-asserted-by":"crossref","first-page":"8665","DOI":"10.1038\/srep08665","article-title":"Understanding the influence of all nodes in a network","volume":"5","author":"Lawyer","year":"2015","journal-title":"Sci Rep."},{"key":"2024032920255669400_msae033-B12","author":"Meyer","year":"2023"},{"issue":"6","key":"2024032920255669400_msae033-B13","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.tree.2012.01.016","article-title":"A model of developmental evolution: selection, pleiotropy and compensation","volume":"27","author":"Pavlicev","year":"2012","journal-title":"Trends Ecol Evol"},{"issue":"1","key":"2024032920255669400_msae033-B14","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41576-018-0069-z","article-title":"The causes of evolvability and their evolution","volume":"20","author":"Payne","year":"2019","journal-title":"Nat Rev Genet."},{"issue":"1","key":"2024032920255669400_msae033-B15","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1101\/gr.097857.109","article-title":"Detection of nonneutral substitution rates on mammalian phylogenies","volume":"20","author":"Pollard","year":"2010","journal-title":"Genome Res"},{"issue":"1545","key":"2024032920255669400_msae033-B16","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1098\/rspb.2004.2732","article-title":"Protein networks, pleiotropy and the evolution of senescence","volume":"271","author":"Promislow","year":"2004","journal-title":"Proc Biol Sci."},{"issue":"3","key":"2024032920255669400_msae033-B17","doi-asserted-by":"crossref","first-page":"e0171920","DOI":"10.1371\/journal.pone.0171920","article-title":"Evolution of protein-protein interaction networks in yeast","volume":"12","author":"Schoenrock","year":"2017","journal-title":"PLoS One"},{"key":"2024032920255669400_msae033-B18","author":"Siriseriwan","year":"2022"},{"issue":"D1","key":"2024032920255669400_msae033-B19","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"2024032920255669400_msae033-B20","doi-asserted-by":"crossref","first-page":"D362","DOI":"10.1093\/nar\/gkw937","article-title":"The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible","volume":"45","author":"Szklarczyk","year":"2017","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"2024032920255669400_msae033-B21","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/gbe\/evy013","article-title":"Comparative genomics reveals accelerated evolution in conserved pathways during the diversification of anole lizards","volume":"10","author":"Tollis","year":"2018","journal-title":"Genome Biol Evol"},{"issue":"8","key":"2024032920255669400_msae033-B22","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1093\/molbev\/msz099","article-title":"Return to the sea, get huge, beat cancer: an analysis of cetacean genomes including an assembly for the humpback whale (Megaptera novaeangliae)","volume":"36","author":"Tollis","year":"2019","journal-title":"Mol Biol Evol."},{"issue":"7186","key":"2024032920255669400_msae033-B23","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nature06756","article-title":"Pleiotropic scaling of gene effects and the \u201ccost of complexity\u201d","volume":"452","author":"Wagner","year":"2008","journal-title":"Nature"},{"issue":"42","key":"2024032920255669400_msae033-B24","doi-asserted-by":"crossref","first-page":"18034","DOI":"10.1073\/pnas.1004666107","article-title":"Genomic patterns of pleiotropy and the evolution of complexity","volume":"107","author":"Wang","year":"2010","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"1","key":"2024032920255669400_msae033-B25","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s12862-020-01613-8","article-title":"Aligning functional network constraint to evolutionary outcomes","volume":"20","author":"Wollenberg Valero","year":"2020","journal-title":"BMC Evol. Biol"},{"key":"2024032920255669400_msae033-B26","first-page":"1049","article-title":"Functional genomics of abiotic environmental adaptation in lacertid lizards and other vertebrates","volume":"91","author":"Wollenberg Valero","year":"2021","journal-title":"J Anim Ecol."},{"issue":"6215","key":"2024032920255669400_msae033-B27","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1126\/science.1251385","article-title":"Comparative genomics reveals insights into avian genome evolution and adaptation","volume":"346","author":"Zhang","year":"2014","journal-title":"Science"}],"container-title":["Molecular Biology and Evolution"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/mbe\/advance-article-pdf\/doi\/10.1093\/molbev\/msae033\/56689950\/msae033.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mbe\/article-pdf\/41\/3\/msae033\/57087144\/msae033.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mbe\/article-pdf\/41\/3\/msae033\/57087144\/msae033.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T20:26:23Z","timestamp":1711743983000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mbe\/article\/doi\/10.1093\/molbev\/msae033\/7609231"}},"subtitle":[],"editor":[{"given":"Emma","family":"Teeling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,2,16]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3,1]]}},"URL":"https:\/\/doi.org\/10.1093\/molbev\/msae033","relation":{},"ISSN":["0737-4038","1537-1719"],"issn-type":[{"value":"0737-4038","type":"print"},{"value":"1537-1719","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,3]]},"published":{"date-parts":[[2024,2,16]]},"article-number":"msae033"}}