The potential of VKORC1 polymorphisms in Mustelidae for evolving anticoagulant resistance through selection along the food chain
In response to strong selection, new mutations can arise quickly and sweep through populations, particularly, if survival and reproduction depend on certain allele copies for adaptation to rapidly changing environments, like resistance against deadly diseases or strong toxins. Since the 1950s, resis...
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description | In response to strong selection, new mutations can arise quickly and sweep through populations, particularly, if survival and reproduction depend on certain allele copies for adaptation to rapidly changing environments, like resistance against deadly diseases or strong toxins. Since the 1950s, resistance to anticoagulant rodenticides in several rodents has emerged through single nucleotide mutations in the vitamin-K-epoxid-reductase-complex-subunit-1 (VKORC1) gene, often located in its exon 3. Detection of high prevalence and concentrations of anticoagulant rodenticides in non-target vertebrates, including carnivorous Mustelidae, let us assume that secondary exposure by feeding on poisoned prey may also cause selection along the food chain and we hypothesized that VKORC1-based resistance might also have evolved in rodents' predators. Using newly-developed mustelid-specific primers for direct sequencing of genomic DNA, we studied VKORC1-DNA-polymorphisms in 115 mustelids of five species (Martes martes, M. foina, Mustela nivalis, M. erminea, M. putorius), obtained from northern Denmark, yielding six sites with nonsynonymous and several synonymous amino acid polymorphisms in exon 3. Comparison of these VKORC1-genotypes with hepatic rodenticide residues (obtained by HPLC combined with fluorescence or mass spectrometry) in 83 individuals (except M. martes), using generalized linear models, suggested that anticoagulant levels depended on species and specific polymorphisms. Although most VKORC-1 polymorphisms may present standing genetic variation, some are situated in resistance-mediating membrane parts of the VKORC1-encoded protein, and might be a result of selection due to exposure to anticoagulant poisons. Our new molecular markers might allow detecting indirect effects of anticoagulant rodenticides on rodent predator populations in the future. |
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Since the 1950s, resistance to anticoagulant rodenticides in several rodents has emerged through single nucleotide mutations in the vitamin-K-epoxid-reductase-complex-subunit-1 (VKORC1) gene, often located in its exon 3. Detection of high prevalence and concentrations of anticoagulant rodenticides in non-target vertebrates, including carnivorous Mustelidae, let us assume that secondary exposure by feeding on poisoned prey may also cause selection along the food chain and we hypothesized that VKORC1-based resistance might also have evolved in rodents' predators. Using newly-developed mustelid-specific primers for direct sequencing of genomic DNA, we studied VKORC1-DNA-polymorphisms in 115 mustelids of five species (Martes martes, M. foina, Mustela nivalis, M. erminea, M. putorius), obtained from northern Denmark, yielding six sites with nonsynonymous and several synonymous amino acid polymorphisms in exon 3. Comparison of these VKORC1-genotypes with hepatic rodenticide residues (obtained by HPLC combined with fluorescence or mass spectrometry) in 83 individuals (except M. martes), using generalized linear models, suggested that anticoagulant levels depended on species and specific polymorphisms. Although most VKORC-1 polymorphisms may present standing genetic variation, some are situated in resistance-mediating membrane parts of the VKORC1-encoded protein, and might be a result of selection due to exposure to anticoagulant poisons. Our new molecular markers might allow detecting indirect effects of anticoagulant rodenticides on rodent predator populations in the future.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0221706</identifier><identifier>PMID: 31465484</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adaptation ; Amino acids ; Amino Acids - genetics ; Animals ; Anticoagulants ; Anticoagulants - pharmacology ; Aquaculture ; Binding sites ; Biology and Life Sciences ; Changing environments ; Denmark ; Deoxyribonucleic acid ; DNA ; DNA sequencing ; Ecology and Environmental Sciences ; Environmental changes ; Exons - genetics ; Exposure ; Fisheries ; Fluorescence ; Food Chain ; Food chains ; Food selection ; Freshwater ecology ; Gene sequencing ; Genes ; Genetic aspects ; Genetic diversity ; Genetic polymorphisms ; Genetic research ; Genotypes ; Geography ; High performance liquid chromatography ; Insecticide resistance ; Introns - genetics ; Liquid chromatography ; Martes martes ; Mass spectrometry ; Mass spectroscopy ; Mustelidae ; Mustelidae - genetics ; Mutation ; Nucleotides ; Physical sciences ; Poisons ; Polymorphism, Genetic ; Population genetics ; Populations ; Predators ; Prey ; Primers ; Proteins ; Reductase ; Reductases ; Research and Analysis Methods ; Rodenticides ; Rodents ; Soil sciences ; Spectroscopy ; Statistical models ; Systematic review ; Toxins ; Vertebrates ; Vitamin K Epoxide Reductases - genetics ; Vitamins</subject><ispartof>PloS one, 2019-08, Vol.14 (8), p.e0221706</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Stöck et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Stöck et al 2019 Stöck et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-a36f9ee62437d618197575513aef13329572aa3553020cc4f3123762bcb932af3</citedby><cites>FETCH-LOGICAL-c692t-a36f9ee62437d618197575513aef13329572aa3553020cc4f3123762bcb932af3</cites><orcidid>0000-0003-4888-8371</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715177/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715177/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23868,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31465484$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Palsson, Arnar</contributor><creatorcontrib>Stöck, Matthias</creatorcontrib><creatorcontrib>Reisch, Florian</creatorcontrib><creatorcontrib>Elmeros, Morten</creatorcontrib><creatorcontrib>Gabriel, Doreen</creatorcontrib><creatorcontrib>Kloas, Werner</creatorcontrib><creatorcontrib>Kreuz, Eva</creatorcontrib><creatorcontrib>Lassen, Pia</creatorcontrib><creatorcontrib>Esther, Alexandra</creatorcontrib><title>The potential of VKORC1 polymorphisms in Mustelidae for evolving anticoagulant resistance through selection along the food chain</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>In response to strong selection, new mutations can arise quickly and sweep through populations, particularly, if survival and reproduction depend on certain allele copies for adaptation to rapidly changing environments, like resistance against deadly diseases or strong toxins. Since the 1950s, resistance to anticoagulant rodenticides in several rodents has emerged through single nucleotide mutations in the vitamin-K-epoxid-reductase-complex-subunit-1 (VKORC1) gene, often located in its exon 3. Detection of high prevalence and concentrations of anticoagulant rodenticides in non-target vertebrates, including carnivorous Mustelidae, let us assume that secondary exposure by feeding on poisoned prey may also cause selection along the food chain and we hypothesized that VKORC1-based resistance might also have evolved in rodents' predators. Using newly-developed mustelid-specific primers for direct sequencing of genomic DNA, we studied VKORC1-DNA-polymorphisms in 115 mustelids of five species (Martes martes, M. foina, Mustela nivalis, M. erminea, M. putorius), obtained from northern Denmark, yielding six sites with nonsynonymous and several synonymous amino acid polymorphisms in exon 3. Comparison of these VKORC1-genotypes with hepatic rodenticide residues (obtained by HPLC combined with fluorescence or mass spectrometry) in 83 individuals (except M. martes), using generalized linear models, suggested that anticoagulant levels depended on species and specific polymorphisms. Although most VKORC-1 polymorphisms may present standing genetic variation, some are situated in resistance-mediating membrane parts of the VKORC1-encoded protein, and might be a result of selection due to exposure to anticoagulant poisons. Our new molecular markers might allow detecting indirect effects of anticoagulant rodenticides on rodent predator populations in the future.</description><subject>Adaptation</subject><subject>Amino acids</subject><subject>Amino Acids - genetics</subject><subject>Animals</subject><subject>Anticoagulants</subject><subject>Anticoagulants - pharmacology</subject><subject>Aquaculture</subject><subject>Binding sites</subject><subject>Biology and Life Sciences</subject><subject>Changing environments</subject><subject>Denmark</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA sequencing</subject><subject>Ecology and Environmental Sciences</subject><subject>Environmental changes</subject><subject>Exons - genetics</subject><subject>Exposure</subject><subject>Fisheries</subject><subject>Fluorescence</subject><subject>Food Chain</subject><subject>Food chains</subject><subject>Food selection</subject><subject>Freshwater ecology</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic polymorphisms</subject><subject>Genetic research</subject><subject>Genotypes</subject><subject>Geography</subject><subject>High performance liquid chromatography</subject><subject>Insecticide resistance</subject><subject>Introns - genetics</subject><subject>Liquid chromatography</subject><subject>Martes martes</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Mustelidae</subject><subject>Mustelidae - genetics</subject><subject>Mutation</subject><subject>Nucleotides</subject><subject>Physical sciences</subject><subject>Poisons</subject><subject>Polymorphism, Genetic</subject><subject>Population genetics</subject><subject>Populations</subject><subject>Predators</subject><subject>Prey</subject><subject>Primers</subject><subject>Proteins</subject><subject>Reductase</subject><subject>Reductases</subject><subject>Research and Analysis Methods</subject><subject>Rodenticides</subject><subject>Rodents</subject><subject>Soil sciences</subject><subject>Spectroscopy</subject><subject>Statistical models</subject><subject>Systematic review</subject><subject>Toxins</subject><subject>Vertebrates</subject><subject>Vitamin K Epoxide Reductases - genetics</subject><subject>Vitamins</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11v0zAUhiMEYmPwDxBYQkJw0eKP2E5ukKaKj4qhSmPs1nKdk8SVGxc7qdgdPx1n7aYW7QLlItbJ8772eZ2TZS8JnhImyYeVH0Kn3XTjO5hiSonE4lF2SkpGJ4Ji9vhgfZI9i3GFMWeFEE-zE0ZywfMiP83-XLWANr6HrrfaIV-j62-LyxlJNXez9mHT2riOyHbo-xB7cLbSgGofEGy929quQTopjdfN4NIKBYg29rozgPo2-KFpUQQHpre-Q9r5JOjb0cFXyLTads-zJ7V2EV7s32fZz8-frmZfJxeLL_PZ-cXEiJL2E81EXQIImjNZCVKQUnLJOWEaasIYLbmkWjPOGabYmLxmhDIp6NIsUwi6ZmfZ653vxvmo9uFFRWlBRcFxgRMx3xGV1yu1CXatw43y2qrbgg-N0iH16kAZWVQmx8xUZZVLapYcygJzgoUAyrhJXh_3uw3LNVQmxRu0OzI9_tLZVjV-q4QknEiZDN7tDYL_NUDs1dpGAy6FDH64PTcjJKd0PPebf9CHu9tTjU4N2K72aV8zmqpzXsqC8JKIRE0foNJTwTrdcge1TfUjwfsjQWJ6-N03eohRzX9c_j-7uD5m3x6wLWjXt9G7YfyP4jGY70ATfIwB6vuQCVbjoNylocZBUftBSbJXhxd0L7qbDPYXSWsODw</recordid><startdate>20190829</startdate><enddate>20190829</enddate><creator>Stöck, Matthias</creator><creator>Reisch, Florian</creator><creator>Elmeros, Morten</creator><creator>Gabriel, Doreen</creator><creator>Kloas, Werner</creator><creator>Kreuz, Eva</creator><creator>Lassen, Pia</creator><creator>Esther, Alexandra</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-4888-8371</orcidid></search><sort><creationdate>20190829</creationdate><title>The potential of VKORC1 polymorphisms in Mustelidae for evolving anticoagulant resistance through selection along the food chain</title><author>Stöck, Matthias ; Reisch, Florian ; Elmeros, Morten ; Gabriel, Doreen ; Kloas, Werner ; Kreuz, Eva ; Lassen, Pia ; Esther, Alexandra</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-a36f9ee62437d618197575513aef13329572aa3553020cc4f3123762bcb932af3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adaptation</topic><topic>Amino acids</topic><topic>Amino Acids - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stöck, Matthias</au><au>Reisch, Florian</au><au>Elmeros, Morten</au><au>Gabriel, Doreen</au><au>Kloas, Werner</au><au>Kreuz, Eva</au><au>Lassen, Pia</au><au>Esther, Alexandra</au><au>Palsson, Arnar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The potential of VKORC1 polymorphisms in Mustelidae for evolving anticoagulant resistance through selection along the food chain</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-08-29</date><risdate>2019</risdate><volume>14</volume><issue>8</issue><spage>e0221706</spage><pages>e0221706-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>In response to strong selection, new mutations can arise quickly and sweep through populations, particularly, if survival and reproduction depend on certain allele copies for adaptation to rapidly changing environments, like resistance against deadly diseases or strong toxins. Since the 1950s, resistance to anticoagulant rodenticides in several rodents has emerged through single nucleotide mutations in the vitamin-K-epoxid-reductase-complex-subunit-1 (VKORC1) gene, often located in its exon 3. Detection of high prevalence and concentrations of anticoagulant rodenticides in non-target vertebrates, including carnivorous Mustelidae, let us assume that secondary exposure by feeding on poisoned prey may also cause selection along the food chain and we hypothesized that VKORC1-based resistance might also have evolved in rodents' predators. Using newly-developed mustelid-specific primers for direct sequencing of genomic DNA, we studied VKORC1-DNA-polymorphisms in 115 mustelids of five species (Martes martes, M. foina, Mustela nivalis, M. erminea, M. putorius), obtained from northern Denmark, yielding six sites with nonsynonymous and several synonymous amino acid polymorphisms in exon 3. Comparison of these VKORC1-genotypes with hepatic rodenticide residues (obtained by HPLC combined with fluorescence or mass spectrometry) in 83 individuals (except M. martes), using generalized linear models, suggested that anticoagulant levels depended on species and specific polymorphisms. Although most VKORC-1 polymorphisms may present standing genetic variation, some are situated in resistance-mediating membrane parts of the VKORC1-encoded protein, and might be a result of selection due to exposure to anticoagulant poisons. Our new molecular markers might allow detecting indirect effects of anticoagulant rodenticides on rodent predator populations in the future.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31465484</pmid><doi>10.1371/journal.pone.0221706</doi><tpages>e0221706</tpages><orcidid>https://orcid.org/0000-0003-4888-8371</orcidid><oa>free_for_read</oa></addata></record> |
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language | eng |
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source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Adaptation Amino acids Amino Acids - genetics Animals Anticoagulants Anticoagulants - pharmacology Aquaculture Binding sites Biology and Life Sciences Changing environments Denmark Deoxyribonucleic acid DNA DNA sequencing Ecology and Environmental Sciences Environmental changes Exons - genetics Exposure Fisheries Fluorescence Food Chain Food chains Food selection Freshwater ecology Gene sequencing Genes Genetic aspects Genetic diversity Genetic polymorphisms Genetic research Genotypes Geography High performance liquid chromatography Insecticide resistance Introns - genetics Liquid chromatography Martes martes Mass spectrometry Mass spectroscopy Mustelidae Mustelidae - genetics Mutation Nucleotides Physical sciences Poisons Polymorphism, Genetic Population genetics Populations Predators Prey Primers Proteins Reductase Reductases Research and Analysis Methods Rodenticides Rodents Soil sciences Spectroscopy Statistical models Systematic review Toxins Vertebrates Vitamin K Epoxide Reductases - genetics Vitamins |
title | The potential of VKORC1 polymorphisms in Mustelidae for evolving anticoagulant resistance through selection along the food chain |
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