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Here, we assess patterns of population differentiation in expressed venom proteins in Northern Pacific rattlesnakes (<jats:italic>Crotalus oreganus<\/jats:italic>) from 13 locations across California. We evaluate the relative importance of major biotic (prey species community composition), abiotic (temperature, precipitation and elevation) and genetic factors (genetic distance based on RAD\u2010seq loci) as correlates of population divergence in venom phenotypes. We found that over half of the variation in venom composition is associated with among\u2010population differentiation for genetic and environmental variables and that this variation occurred along axes defining previously observed functional trade\u2010offs between venom proteins that have neurotoxic, myotoxic and hemorrhagic effects. Surprisingly, genetic differentiation among populations was the best predictor of venom divergence, accounting for 46% of overall variation, whereas differences in prey community composition and abiotic factors explained smaller amounts of variation (23% and 19%, respectively). The association between genetic differentiation and venom composition could be due to an isolation\u2010by\u2010distance effect or, more likely, an isolation\u2010by\u2010environment effect where selection against recent migrants is strong, producing a correlation between neutral genetic differentiation and venom differentiation. Our findings suggest that even coarse estimates of prey community composition can be useful in understanding the selection pressures acting on patterns of venom protein expression. Additionally, our results suggest that factors other than adaptation to spatial variation in prey need to be considered when explaining population divergence in venom.<\/jats:p>","DOI":"10.1111\/jeb.13347","type":"journal-article","created":{"date-parts":[[2018,6,30]],"date-time":"2018-06-30T13:34:21Z","timestamp":1530365661000},"page":"1513-1528","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Local prey community composition and genetic distance predict venom divergence among populations of the northern Pacific rattlesnake (<i>Crotalus oreganus<\/i>)"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3477-3012","authenticated-orcid":false,"given":"Matthew L.","family":"Holding","sequence":"first","affiliation":[{"name":"Department of Evolution, Ecology, and Organismal Biology The Ohio State University Columbus OH USA"},{"name":"Department of Biological Sciences Florida State University Tallahassee FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Margres","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Florida State University Tallahassee FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darin R.","family":"Rokyta","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Florida State University Tallahassee FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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