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Snake venoms are highly variable modular systems that exhibit extreme diversification even across very short time scales. One well-studied venom phenotype dichotomy is a trade-off between neurotoxicity versus hemotoxicity that occurs through the high expression of a heterodimeric neurotoxic phospholipase A<jats:sub>2<\/jats:sub>(PLA<jats:sub>2<\/jats:sub>) or snake venom metalloproteinases (SVMPs). We tested whether the variation in these venom phenotypes could occur via variation in regulatory sub-modules through comparative venom gland transcriptomics of representative Black-Speckled Palm-Pitvipers (<jats:italic>Bothriechis nigroviridis<\/jats:italic>) and Talamancan Palm-Pitvipers (<jats:italic>B. nubestris<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We assembled 1517 coding sequences, including 43 toxins for<jats:italic>B. nigroviridis<\/jats:italic>and 1787 coding sequences including 42 toxins for<jats:italic>B. nubestris<\/jats:italic>. The venom gland transcriptomes were extremely divergent between these two species with one<jats:italic>B. nigroviridis<\/jats:italic>exhibiting a primarily neurotoxic pattern of expression, both<jats:italic>B. nubestris<\/jats:italic>expressing primarily hemorrhagic toxins, and a second<jats:italic>B. nigroviridis<\/jats:italic>exhibiting a mixed expression phenotype. Weighted gene coexpression analyses identified six submodules of transcript expression variation, one of which was highly associated with SVMPs and a second which contained both subunits of the neurotoxic PLA<jats:sub>2<\/jats:sub>complex. The sub-module association of these toxins suggest common regulatory pathways underlie the variation in their expression and is consistent with known patterns of inheritance of similar haplotypes in other species. We also find evidence that module associated toxin families show fewer gene duplications and transcript losses between species, but module association did not appear to affect sequence diversification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Sub-modular regulation of expression likely contributes to the diversification of venom phenotypes within and among species and underscores the role of modularity in facilitating rapid evolution of complex traits.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12864-020-6545-9","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T15:02:51Z","timestamp":1581433371000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Trait differentiation and modular toxin expression in palm-pitvipers"],"prefix":"10.1186","volume":"21","author":[{"given":"Andrew J.","family":"Mason","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Margres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason L.","family":"Strickland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darin R.","family":"Rokyta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmood","family":"Sasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2020-6992","authenticated-orcid":false,"given":"Christopher L.","family":"Parkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,11]]},"reference":[{"issue":"12","key":"6545_CR1","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1038\/nrg2267","volume":"8","author":"GP Wagner","year":"2007","unstructured":"Wagner GP, Pavlicev M, Cheverud JM. 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Project protocols were also submitted to and approved locally in Costa Rica by the Universidad de Costa Rica\u2019s Animal Care Office (Comit\u00e9 Institucional para el Cuidado y Uso de los Animales) permit CICUA-082-17. Samples were collected and exported from Costa Rica under Sistema Nacional de \u00e1reas conservaci\u00f3n (SINAC) Investigation Permit 040-2016-INV-ACAT. Permission to collect samples used in this study was received from SINAC and property owners of sites from which animals were collected.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"147"}}