Genomic Signatures of a Major Adaptive Event in the Pathogenic Fungus Melampsora larici-populina

Abstract The recent availability of genome-wide sequencing techniques has allowed systematic screening for molecular signatures of adaptation, including in nonmodel organisms. Host–pathogen interactions constitute good models due to the strong selective pressures that they entail. We focused on an a...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Genome biology and evolution 2022-01, Vol.14 (1)
Hauptverfasser: Persoons, Antoine, Maupetit, Agathe, Louet, Clémentine, Andrieux, Axelle, Lipzen, Anna, Barry, Kerrie W, Na, Hyunsoo, Adam, Catherine, Grigoriev, Igor V, Segura, Vincent, Duplessis, Sébastien, Frey, Pascal, Halkett, Fabien, De Mita, Stéphane
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page
container_issue 1
container_start_page
container_title Genome biology and evolution
container_volume 14
creator Persoons, Antoine
Maupetit, Agathe
Louet, Clémentine
Andrieux, Axelle
Lipzen, Anna
Barry, Kerrie W
Na, Hyunsoo
Adam, Catherine
Grigoriev, Igor V
Segura, Vincent
Duplessis, Sébastien
Frey, Pascal
Halkett, Fabien
De Mita, Stéphane
description Abstract The recent availability of genome-wide sequencing techniques has allowed systematic screening for molecular signatures of adaptation, including in nonmodel organisms. Host–pathogen interactions constitute good models due to the strong selective pressures that they entail. We focused on an adaptive event which affected the poplar rust fungus Melampsora larici-populina when it overcame a resistance gene borne by its host, cultivated poplar. Based on 76 virulent and avirulent isolates framing narrowly the estimated date of the adaptive event, we examined the molecular signatures of selection. Using an array of genome scan methods based on different features of nucleotide diversity, we detected a single locus exhibiting a consistent pattern suggestive of a selective sweep in virulent individuals (excess of differentiation between virulent and avirulent samples, linkage disequilibrium, genotype–phenotype statistical association, and long-range haplotypes). Our study pinpoints a single gene and further a single amino acid replacement which may have allowed the adaptive event. Although our samples are nearly contemporary to the selective sweep, it does not seem to have affected genome diversity further than the immediate vicinity of the causal locus, which can be explained by a soft selective sweep (where selection acts on standing variation) and by the impact of recombination in mitigating the impact of selection. Therefore, it seems that properties of the life cycle of M. larici-populina, which entails both high genetic diversity and outbreeding, has facilitated its adaptation.
doi_str_mv 10.1093/gbe/evab279
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8755504</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/gbe/evab279</oup_id><sourcerecordid>2611667246</sourcerecordid><originalsourceid>FETCH-LOGICAL-c473t-3f139090bc36a1d552a6e449852ae50a2aa6ee885bf8eeb9cc11bee478200bb63</originalsourceid><addsrcrecordid>eNp9kc-L1DAUx4Mo7rp68i7BgyhSN2matLkIw7I_hFkU1HNMM69tljapSVrwvzfDjMvqwVNeXj758B5fhF5S8oESyc77Fs5h1W1Zy0folNZcFkJw9vhBfYKexXhHiBCVYE_RCasklaJuTtGPa3B-sgZ_tb3TaQkQse-wxrf6zge82ek52RXw5QouYetwGgB_0WnwPbj87Wpx_RLxLYx6mqMPGo86WGOL2c_LaJ1-jp50eozw4nieoe9Xl98ubort5-tPF5ttYaqapYJ1lEkiSWuY0HTHeakFVJVscgGc6FLnOzQNb7sGoJXGUNoCVHVTEtK2gp2hjwfvvLQT7EweN-hRzcFOOvxSXlv194uzg-r9qpqac06qLHh9EPiYrIrGJjCD8c6BSYo2sqQNydC7AzT8477ZbNW-R5ggoiR8pZl9e5wo-J8LxKQmGw2Mo3bgl6hKQakQdVnth39_QE3wMQbo7t2UqH3IKoesjiFn-tXDVe_ZP6lm4M1xlWX-r-k35C2xRg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2611667246</pqid></control><display><type>article</type><title>Genomic Signatures of a Major Adaptive Event in the Pathogenic Fungus Melampsora larici-populina</title><source>Oxford Journals Open Access Collection</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Persoons, Antoine ; Maupetit, Agathe ; Louet, Clémentine ; Andrieux, Axelle ; Lipzen, Anna ; Barry, Kerrie W ; Na, Hyunsoo ; Adam, Catherine ; Grigoriev, Igor V ; Segura, Vincent ; Duplessis, Sébastien ; Frey, Pascal ; Halkett, Fabien ; De Mita, Stéphane</creator><creatorcontrib>Persoons, Antoine ; Maupetit, Agathe ; Louet, Clémentine ; Andrieux, Axelle ; Lipzen, Anna ; Barry, Kerrie W ; Na, Hyunsoo ; Adam, Catherine ; Grigoriev, Igor V ; Segura, Vincent ; Duplessis, Sébastien ; Frey, Pascal ; Halkett, Fabien ; De Mita, Stéphane ; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)</creatorcontrib><description>Abstract The recent availability of genome-wide sequencing techniques has allowed systematic screening for molecular signatures of adaptation, including in nonmodel organisms. Host–pathogen interactions constitute good models due to the strong selective pressures that they entail. We focused on an adaptive event which affected the poplar rust fungus Melampsora larici-populina when it overcame a resistance gene borne by its host, cultivated poplar. Based on 76 virulent and avirulent isolates framing narrowly the estimated date of the adaptive event, we examined the molecular signatures of selection. Using an array of genome scan methods based on different features of nucleotide diversity, we detected a single locus exhibiting a consistent pattern suggestive of a selective sweep in virulent individuals (excess of differentiation between virulent and avirulent samples, linkage disequilibrium, genotype–phenotype statistical association, and long-range haplotypes). Our study pinpoints a single gene and further a single amino acid replacement which may have allowed the adaptive event. Although our samples are nearly contemporary to the selective sweep, it does not seem to have affected genome diversity further than the immediate vicinity of the causal locus, which can be explained by a soft selective sweep (where selection acts on standing variation) and by the impact of recombination in mitigating the impact of selection. Therefore, it seems that properties of the life cycle of M. larici-populina, which entails both high genetic diversity and outbreeding, has facilitated its adaptation.</description><identifier>ISSN: 1759-6653</identifier><identifier>EISSN: 1759-6653</identifier><identifier>DOI: 10.1093/gbe/evab279</identifier><identifier>PMID: 34919678</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>BASIC BIOLOGICAL SCIENCES ; Basidiomycota ; coevolution ; genome scan ; genome-wide association studies ; Genomics ; Life Sciences ; Plant Diseases - microbiology ; plant-pathogen interactions ; Population genomics ; Populus - genetics</subject><ispartof>Genome biology and evolution, 2022-01, Vol.14 (1)</ispartof><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. 2021</rights><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.</rights><rights>Attribution - NonCommercial</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-3f139090bc36a1d552a6e449852ae50a2aa6ee885bf8eeb9cc11bee478200bb63</citedby><cites>FETCH-LOGICAL-c473t-3f139090bc36a1d552a6e449852ae50a2aa6ee885bf8eeb9cc11bee478200bb63</cites><orcidid>0000-0002-3136-8903 ; 0000-0003-2752-865X ; 0000-0003-2293-9329 ; 0000-0001-6294-737X ; 0000-0002-2072-2989 ; 0000-0001-8856-0501 ; 0000-0002-2003-9776 ; 0000-0003-1860-2256 ; 0000-0002-8999-6785 ; 0000-0002-9749-6940 ; 000000032752865X ; 0000000231368903</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/PMC8755504/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8755504/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1598,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34919678$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.univ-lorraine.fr/hal-03606205$$DView record in HAL$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/servlets/purl/1892180$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Persoons, Antoine</creatorcontrib><creatorcontrib>Maupetit, Agathe</creatorcontrib><creatorcontrib>Louet, Clémentine</creatorcontrib><creatorcontrib>Andrieux, Axelle</creatorcontrib><creatorcontrib>Lipzen, Anna</creatorcontrib><creatorcontrib>Barry, Kerrie W</creatorcontrib><creatorcontrib>Na, Hyunsoo</creatorcontrib><creatorcontrib>Adam, Catherine</creatorcontrib><creatorcontrib>Grigoriev, Igor V</creatorcontrib><creatorcontrib>Segura, Vincent</creatorcontrib><creatorcontrib>Duplessis, Sébastien</creatorcontrib><creatorcontrib>Frey, Pascal</creatorcontrib><creatorcontrib>Halkett, Fabien</creatorcontrib><creatorcontrib>De Mita, Stéphane</creatorcontrib><creatorcontrib>Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)</creatorcontrib><title>Genomic Signatures of a Major Adaptive Event in the Pathogenic Fungus Melampsora larici-populina</title><title>Genome biology and evolution</title><addtitle>Genome Biol Evol</addtitle><description>Abstract The recent availability of genome-wide sequencing techniques has allowed systematic screening for molecular signatures of adaptation, including in nonmodel organisms. Host–pathogen interactions constitute good models due to the strong selective pressures that they entail. We focused on an adaptive event which affected the poplar rust fungus Melampsora larici-populina when it overcame a resistance gene borne by its host, cultivated poplar. Based on 76 virulent and avirulent isolates framing narrowly the estimated date of the adaptive event, we examined the molecular signatures of selection. Using an array of genome scan methods based on different features of nucleotide diversity, we detected a single locus exhibiting a consistent pattern suggestive of a selective sweep in virulent individuals (excess of differentiation between virulent and avirulent samples, linkage disequilibrium, genotype–phenotype statistical association, and long-range haplotypes). Our study pinpoints a single gene and further a single amino acid replacement which may have allowed the adaptive event. Although our samples are nearly contemporary to the selective sweep, it does not seem to have affected genome diversity further than the immediate vicinity of the causal locus, which can be explained by a soft selective sweep (where selection acts on standing variation) and by the impact of recombination in mitigating the impact of selection. Therefore, it seems that properties of the life cycle of M. larici-populina, which entails both high genetic diversity and outbreeding, has facilitated its adaptation.</description><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>Basidiomycota</subject><subject>coevolution</subject><subject>genome scan</subject><subject>genome-wide association studies</subject><subject>Genomics</subject><subject>Life Sciences</subject><subject>Plant Diseases - microbiology</subject><subject>plant-pathogen interactions</subject><subject>Population genomics</subject><subject>Populus - genetics</subject><issn>1759-6653</issn><issn>1759-6653</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNp9kc-L1DAUx4Mo7rp68i7BgyhSN2matLkIw7I_hFkU1HNMM69tljapSVrwvzfDjMvqwVNeXj758B5fhF5S8oESyc77Fs5h1W1Zy0folNZcFkJw9vhBfYKexXhHiBCVYE_RCasklaJuTtGPa3B-sgZ_tb3TaQkQse-wxrf6zge82ek52RXw5QouYetwGgB_0WnwPbj87Wpx_RLxLYx6mqMPGo86WGOL2c_LaJ1-jp50eozw4nieoe9Xl98ubort5-tPF5ttYaqapYJ1lEkiSWuY0HTHeakFVJVscgGc6FLnOzQNb7sGoJXGUNoCVHVTEtK2gp2hjwfvvLQT7EweN-hRzcFOOvxSXlv194uzg-r9qpqac06qLHh9EPiYrIrGJjCD8c6BSYo2sqQNydC7AzT8477ZbNW-R5ggoiR8pZl9e5wo-J8LxKQmGw2Mo3bgl6hKQakQdVnth39_QE3wMQbo7t2UqH3IKoesjiFn-tXDVe_ZP6lm4M1xlWX-r-k35C2xRg</recordid><startdate>20220104</startdate><enddate>20220104</enddate><creator>Persoons, Antoine</creator><creator>Maupetit, Agathe</creator><creator>Louet, Clémentine</creator><creator>Andrieux, Axelle</creator><creator>Lipzen, Anna</creator><creator>Barry, Kerrie W</creator><creator>Na, Hyunsoo</creator><creator>Adam, Catherine</creator><creator>Grigoriev, Igor V</creator><creator>Segura, Vincent</creator><creator>Duplessis, Sébastien</creator><creator>Frey, Pascal</creator><creator>Halkett, Fabien</creator><creator>De Mita, Stéphane</creator><general>Oxford University Press</general><general>Society for Molecular Biology and Evolution</general><scope>TOX</scope><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>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>OIOZB</scope><scope>OTOTI</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3136-8903</orcidid><orcidid>https://orcid.org/0000-0003-2752-865X</orcidid><orcidid>https://orcid.org/0000-0003-2293-9329</orcidid><orcidid>https://orcid.org/0000-0001-6294-737X</orcidid><orcidid>https://orcid.org/0000-0002-2072-2989</orcidid><orcidid>https://orcid.org/0000-0001-8856-0501</orcidid><orcidid>https://orcid.org/0000-0002-2003-9776</orcidid><orcidid>https://orcid.org/0000-0003-1860-2256</orcidid><orcidid>https://orcid.org/0000-0002-8999-6785</orcidid><orcidid>https://orcid.org/0000-0002-9749-6940</orcidid><orcidid>https://orcid.org/000000032752865X</orcidid><orcidid>https://orcid.org/0000000231368903</orcidid></search><sort><creationdate>20220104</creationdate><title>Genomic Signatures of a Major Adaptive Event in the Pathogenic Fungus Melampsora larici-populina</title><author>Persoons, Antoine ; Maupetit, Agathe ; Louet, Clémentine ; Andrieux, Axelle ; Lipzen, Anna ; Barry, Kerrie W ; Na, Hyunsoo ; Adam, Catherine ; Grigoriev, Igor V ; Segura, Vincent ; Duplessis, Sébastien ; Frey, Pascal ; Halkett, Fabien ; De Mita, Stéphane</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c473t-3f139090bc36a1d552a6e449852ae50a2aa6ee885bf8eeb9cc11bee478200bb63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>BASIC BIOLOGICAL SCIENCES</topic><topic>Basidiomycota</topic><topic>coevolution</topic><topic>genome scan</topic><topic>genome-wide association studies</topic><topic>Genomics</topic><topic>Life Sciences</topic><topic>Plant Diseases - microbiology</topic><topic>plant-pathogen interactions</topic><topic>Population genomics</topic><topic>Populus - genetics</topic><toplevel>online_resources</toplevel><creatorcontrib>Persoons, Antoine</creatorcontrib><creatorcontrib>Maupetit, Agathe</creatorcontrib><creatorcontrib>Louet, Clémentine</creatorcontrib><creatorcontrib>Andrieux, Axelle</creatorcontrib><creatorcontrib>Lipzen, Anna</creatorcontrib><creatorcontrib>Barry, Kerrie W</creatorcontrib><creatorcontrib>Na, Hyunsoo</creatorcontrib><creatorcontrib>Adam, Catherine</creatorcontrib><creatorcontrib>Grigoriev, Igor V</creatorcontrib><creatorcontrib>Segura, Vincent</creatorcontrib><creatorcontrib>Duplessis, Sébastien</creatorcontrib><creatorcontrib>Frey, Pascal</creatorcontrib><creatorcontrib>Halkett, Fabien</creatorcontrib><creatorcontrib>De Mita, Stéphane</creatorcontrib><creatorcontrib>Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>OSTI.GOV - Hybrid</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genome biology and evolution</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Persoons, Antoine</au><au>Maupetit, Agathe</au><au>Louet, Clémentine</au><au>Andrieux, Axelle</au><au>Lipzen, Anna</au><au>Barry, Kerrie W</au><au>Na, Hyunsoo</au><au>Adam, Catherine</au><au>Grigoriev, Igor V</au><au>Segura, Vincent</au><au>Duplessis, Sébastien</au><au>Frey, Pascal</au><au>Halkett, Fabien</au><au>De Mita, Stéphane</au><aucorp>Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genomic Signatures of a Major Adaptive Event in the Pathogenic Fungus Melampsora larici-populina</atitle><jtitle>Genome biology and evolution</jtitle><addtitle>Genome Biol Evol</addtitle><date>2022-01-04</date><risdate>2022</risdate><volume>14</volume><issue>1</issue><issn>1759-6653</issn><eissn>1759-6653</eissn><abstract>Abstract The recent availability of genome-wide sequencing techniques has allowed systematic screening for molecular signatures of adaptation, including in nonmodel organisms. Host–pathogen interactions constitute good models due to the strong selective pressures that they entail. We focused on an adaptive event which affected the poplar rust fungus Melampsora larici-populina when it overcame a resistance gene borne by its host, cultivated poplar. Based on 76 virulent and avirulent isolates framing narrowly the estimated date of the adaptive event, we examined the molecular signatures of selection. Using an array of genome scan methods based on different features of nucleotide diversity, we detected a single locus exhibiting a consistent pattern suggestive of a selective sweep in virulent individuals (excess of differentiation between virulent and avirulent samples, linkage disequilibrium, genotype–phenotype statistical association, and long-range haplotypes). Our study pinpoints a single gene and further a single amino acid replacement which may have allowed the adaptive event. Although our samples are nearly contemporary to the selective sweep, it does not seem to have affected genome diversity further than the immediate vicinity of the causal locus, which can be explained by a soft selective sweep (where selection acts on standing variation) and by the impact of recombination in mitigating the impact of selection. Therefore, it seems that properties of the life cycle of M. larici-populina, which entails both high genetic diversity and outbreeding, has facilitated its adaptation.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>34919678</pmid><doi>10.1093/gbe/evab279</doi><orcidid>https://orcid.org/0000-0002-3136-8903</orcidid><orcidid>https://orcid.org/0000-0003-2752-865X</orcidid><orcidid>https://orcid.org/0000-0003-2293-9329</orcidid><orcidid>https://orcid.org/0000-0001-6294-737X</orcidid><orcidid>https://orcid.org/0000-0002-2072-2989</orcidid><orcidid>https://orcid.org/0000-0001-8856-0501</orcidid><orcidid>https://orcid.org/0000-0002-2003-9776</orcidid><orcidid>https://orcid.org/0000-0003-1860-2256</orcidid><orcidid>https://orcid.org/0000-0002-8999-6785</orcidid><orcidid>https://orcid.org/0000-0002-9749-6940</orcidid><orcidid>https://orcid.org/000000032752865X</orcidid><orcidid>https://orcid.org/0000000231368903</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1759-6653
ispartof Genome biology and evolution, 2022-01, Vol.14 (1)
issn 1759-6653
1759-6653
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8755504
source Oxford Journals Open Access Collection; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central
subjects BASIC BIOLOGICAL SCIENCES
Basidiomycota
coevolution
genome scan
genome-wide association studies
Genomics
Life Sciences
Plant Diseases - microbiology
plant-pathogen interactions
Population genomics
Populus - genetics
title Genomic Signatures of a Major Adaptive Event in the Pathogenic Fungus Melampsora larici-populina
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T14%3A35%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genomic%20Signatures%20of%20a%20Major%20Adaptive%20Event%20in%20the%20Pathogenic%20Fungus%20Melampsora%20larici-populina&rft.jtitle=Genome%20biology%20and%20evolution&rft.au=Persoons,%20Antoine&rft.aucorp=Lawrence%20Berkeley%20National%20Lab.%20(LBNL),%20Berkeley,%20CA%20(United%20States)&rft.date=2022-01-04&rft.volume=14&rft.issue=1&rft.issn=1759-6653&rft.eissn=1759-6653&rft_id=info:doi/10.1093/gbe/evab279&rft_dat=%3Cproquest_pubme%3E2611667246%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2611667246&rft_id=info:pmid/34919678&rft_oup_id=10.1093/gbe/evab279&rfr_iscdi=true