biostudies-literatureDobon BAgencia Estatal de InvestigaciónMinisterio de Economía, Industria y Competitividad, Gobierno de EspañaSecretaria d&apos;Universitats i Recerca, Departament d&apos;Economia i Coneixement, Generalitat de CatalunyaMinisterio de Educación, Cultura y DeporteH2020 LEIT Nanotechnologies17https://www.ebi.ac.uk/biostudies/studies/S-EPMC6724310biostudies-literatureUnknown14(1)<h4>Background</h4>Determining the factors involved in the likelihood of a gene being under adaptive selection is still a challenging goal in Evolutionary Biology. Here, we perform an evolutionary analysis of the human metabolic genes to explore the associations between network structure and the presence and strength of natural selection in the genes whose products are involved in metabolism. Purifying and positive selection are estimated at interspecific (among mammals) and intraspecific (among human populations) levels, and the connections between enzymatic reactions are differentiated between incoming (in-degree) and outgoing (out-degree) links.<h4>Results</h4>We confirm that purifying selection has been stronger in highly connected genes. Long-term positive selection has targeted poorlBiology directGene connectivity and enzyme evolution in the human metabolic network.PMC6724310BFU2016-77961-P210491758GRC 2017 527 SGR 702FPU13/06813BIO2015–66960-C3–1-RMDM-2014-0370Dobon BMontanucci LLaayouni HPereto JBertranpetit JfalseGene connectivity and enzyme evolution in the human metabolic network.<h4>Background</h4>Determining the factors involved in the likelihood of a gene being under adaptive selection is still a challenging goal in Evolutionary Biology. Here, we perform an evolutionary analysis of the human metabolic genes to explore the associations between network structure and the presence and strength of natural selection in the genes whose products are involved in metabolism. Purifying and positive selection are estimated at interspecific (among mammals) and intraspecific (among human populations) levels, and the connections between enzymatic reactions are differentiated between incoming (in-degree) and outgoing (out-degree) links.<h4>Results</h4>We confirm that purifying selection has been stronger in highly connected genes. Long-term positive selection has targeted poorl2019-01-01T00:00:00Z2019 Sep2025-04-05T13:19:32.973Z2019-09-14T07:06:19ZS-EPMC67243103148109710.1186/s13062-019-0248-7