Loading…
Multiple intrasyntenic rearrangements and rapid speciation in voles
Remarkably stable genomic chromosome elements (evolutionary conserved segments or syntenies) are the basis of large-scale chromosome architecture in vertebrate species. However, these syntenic elements harbour evolutionary important changes through intrachromosomal rearrangements such as inversions...
Saved in:
Published in: | Scientific reports 2018-10, Vol.8 (1), p.14980-9, Article 14980 |
---|---|
Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c511t-88aa9e1d9592ed07ef67f0d2edda972138ece50c1d88ea1ee923eb384b8e6e7f3 |
---|---|
cites | cdi_FETCH-LOGICAL-c511t-88aa9e1d9592ed07ef67f0d2edda972138ece50c1d88ea1ee923eb384b8e6e7f3 |
container_end_page | 9 |
container_issue | 1 |
container_start_page | 14980 |
container_title | Scientific reports |
container_volume | 8 |
creator | Romanenko, Svetlana A. Serdyukova, Natalya A. Perelman, Polina L. Trifonov, Vladimir A. Golenishchev, Feodor N. Bulatova, Nina Sh Stanyon, Roscoe Graphodatsky, Alexander S. |
description | Remarkably stable genomic chromosome elements (evolutionary conserved segments or syntenies) are the basis of large-scale chromosome architecture in vertebrate species. However, these syntenic elements harbour evolutionary important changes through intrachromosomal rearrangements such as inversions and centromere repositioning. Here, using FISH with a set of 20 region-specific probes on a wide array of 28 species, we analyzed evolution of three conserved syntenic regions of the Arvicolinae ancestral karyotype. Inside these syntenies we uncovered multiple, previously cryptic intrachromosomal rearrangements. Although in each of the three conserved blocks we found inversions and centromere repositions, the blocks experienced different types of rearrangements. In two syntenies centromere repositioning predominated, while in the third region, paracentric inversions were more frequent, whereas pericentric inversions were not detected. We found that some of the intrachromosomal rearrangements, mainly paracentric inversions, were synapomorphic for whole arvicoline genera or tribes: genera
Alexandromys
and
Microtus
, tribes Ellobini and Myodini. We hypothesize that intrachromosomal rearrangements within conserved syntenic blocks are a major evolutionary force modulating genome architecture in species-rich and rapidly-evolving rodent taxa. Inversions and centromere repositioning may impact speciation and provide a potential link between genome evolution, speciation, and biogeography. |
doi_str_mv | 10.1038/s41598-018-33300-6 |
format | article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6175948</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2117148706</sourcerecordid><originalsourceid>FETCH-LOGICAL-c511t-88aa9e1d9592ed07ef67f0d2edda972138ece50c1d88ea1ee923eb384b8e6e7f3</originalsourceid><addsrcrecordid>eNp9kU1LxDAQhoMoKuv-AQ9S8OKlmkmaNrkIsvgFihc9h2w7XSPdtCatsP_e7Ifrx8FcMjDP-84MLyHHQM-BcnkRMhBKphRkyjmnNM13yCGjmUgZZ2z3R31AxiG80fgEUxmofXLAKVOFAnFIJo9D09uuwcS63puwcD06WyYejffGzXCOrg-JcVXiTWerJHRYWtPb1kVF8tE2GI7IXm2agOPNPyIvN9fPk7v04en2fnL1kJYCoE-lNEYhVEoohhUtsM6LmlaxrowqGHCJJQpaQiUlGkBUjOOUy2wqMcei5iNyufbthukcqxKXGze683Zu_EK3xurfHWdf9az90DkUQmUyGpxtDHz7PmDo9dyGEpvGOGyHoBlAwSWHTET09A_61g7exfNWFGSyoHmk2JoqfRuCx3q7DFC9jEmvY9IxJr2KSS9FJz_P2Eq-QokAXwMhtmIE_nv2P7afv5ufKQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2117148706</pqid></control><display><type>article</type><title>Multiple intrasyntenic rearrangements and rapid speciation in voles</title><source>Open Access: PubMed Central</source><source>Publicly Available Content Database</source><source>Free Full-Text Journals in Chemistry</source><source>Springer Nature - nature.com Journals - Fully Open Access</source><creator>Romanenko, Svetlana A. ; Serdyukova, Natalya A. ; Perelman, Polina L. ; Trifonov, Vladimir A. ; Golenishchev, Feodor N. ; Bulatova, Nina Sh ; Stanyon, Roscoe ; Graphodatsky, Alexander S.</creator><creatorcontrib>Romanenko, Svetlana A. ; Serdyukova, Natalya A. ; Perelman, Polina L. ; Trifonov, Vladimir A. ; Golenishchev, Feodor N. ; Bulatova, Nina Sh ; Stanyon, Roscoe ; Graphodatsky, Alexander S.</creatorcontrib><description>Remarkably stable genomic chromosome elements (evolutionary conserved segments or syntenies) are the basis of large-scale chromosome architecture in vertebrate species. However, these syntenic elements harbour evolutionary important changes through intrachromosomal rearrangements such as inversions and centromere repositioning. Here, using FISH with a set of 20 region-specific probes on a wide array of 28 species, we analyzed evolution of three conserved syntenic regions of the Arvicolinae ancestral karyotype. Inside these syntenies we uncovered multiple, previously cryptic intrachromosomal rearrangements. Although in each of the three conserved blocks we found inversions and centromere repositions, the blocks experienced different types of rearrangements. In two syntenies centromere repositioning predominated, while in the third region, paracentric inversions were more frequent, whereas pericentric inversions were not detected. We found that some of the intrachromosomal rearrangements, mainly paracentric inversions, were synapomorphic for whole arvicoline genera or tribes: genera
Alexandromys
and
Microtus
, tribes Ellobini and Myodini. We hypothesize that intrachromosomal rearrangements within conserved syntenic blocks are a major evolutionary force modulating genome architecture in species-rich and rapidly-evolving rodent taxa. Inversions and centromere repositioning may impact speciation and provide a potential link between genome evolution, speciation, and biogeography.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-018-33300-6</identifier><identifier>PMID: 30297915</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/106 ; 14/32 ; 14/34 ; 14/63 ; 38/77 ; 631/181/2474 ; 631/208/1405 ; Animals ; Arvicolinae - genetics ; Biogeography ; Chromosome Painting ; Chromosomes, Mammalian - genetics ; DNA probes ; Evolution, Molecular ; Evolutionary conservation ; Gene Rearrangement - genetics ; Genetic Speciation ; Genomes ; Humanities and Social Sciences ; Karyotypes ; multidisciplinary ; Phylogeny ; Science ; Science (multidisciplinary) ; Speciation ; Species ; Synteny ; Synteny - genetics</subject><ispartof>Scientific reports, 2018-10, Vol.8 (1), p.14980-9, Article 14980</ispartof><rights>The Author(s) 2018</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c511t-88aa9e1d9592ed07ef67f0d2edda972138ece50c1d88ea1ee923eb384b8e6e7f3</citedby><cites>FETCH-LOGICAL-c511t-88aa9e1d9592ed07ef67f0d2edda972138ece50c1d88ea1ee923eb384b8e6e7f3</cites><orcidid>0000-0002-7229-1092 ; 0000-0002-0951-5209</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2117148706/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2117148706?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30297915$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Romanenko, Svetlana A.</creatorcontrib><creatorcontrib>Serdyukova, Natalya A.</creatorcontrib><creatorcontrib>Perelman, Polina L.</creatorcontrib><creatorcontrib>Trifonov, Vladimir A.</creatorcontrib><creatorcontrib>Golenishchev, Feodor N.</creatorcontrib><creatorcontrib>Bulatova, Nina Sh</creatorcontrib><creatorcontrib>Stanyon, Roscoe</creatorcontrib><creatorcontrib>Graphodatsky, Alexander S.</creatorcontrib><title>Multiple intrasyntenic rearrangements and rapid speciation in voles</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Remarkably stable genomic chromosome elements (evolutionary conserved segments or syntenies) are the basis of large-scale chromosome architecture in vertebrate species. However, these syntenic elements harbour evolutionary important changes through intrachromosomal rearrangements such as inversions and centromere repositioning. Here, using FISH with a set of 20 region-specific probes on a wide array of 28 species, we analyzed evolution of three conserved syntenic regions of the Arvicolinae ancestral karyotype. Inside these syntenies we uncovered multiple, previously cryptic intrachromosomal rearrangements. Although in each of the three conserved blocks we found inversions and centromere repositions, the blocks experienced different types of rearrangements. In two syntenies centromere repositioning predominated, while in the third region, paracentric inversions were more frequent, whereas pericentric inversions were not detected. We found that some of the intrachromosomal rearrangements, mainly paracentric inversions, were synapomorphic for whole arvicoline genera or tribes: genera
Alexandromys
and
Microtus
, tribes Ellobini and Myodini. We hypothesize that intrachromosomal rearrangements within conserved syntenic blocks are a major evolutionary force modulating genome architecture in species-rich and rapidly-evolving rodent taxa. Inversions and centromere repositioning may impact speciation and provide a potential link between genome evolution, speciation, and biogeography.</description><subject>13/106</subject><subject>14/32</subject><subject>14/34</subject><subject>14/63</subject><subject>38/77</subject><subject>631/181/2474</subject><subject>631/208/1405</subject><subject>Animals</subject><subject>Arvicolinae - genetics</subject><subject>Biogeography</subject><subject>Chromosome Painting</subject><subject>Chromosomes, Mammalian - genetics</subject><subject>DNA probes</subject><subject>Evolution, Molecular</subject><subject>Evolutionary conservation</subject><subject>Gene Rearrangement - genetics</subject><subject>Genetic Speciation</subject><subject>Genomes</subject><subject>Humanities and Social Sciences</subject><subject>Karyotypes</subject><subject>multidisciplinary</subject><subject>Phylogeny</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Speciation</subject><subject>Species</subject><subject>Synteny</subject><subject>Synteny - genetics</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNp9kU1LxDAQhoMoKuv-AQ9S8OKlmkmaNrkIsvgFihc9h2w7XSPdtCatsP_e7Ifrx8FcMjDP-84MLyHHQM-BcnkRMhBKphRkyjmnNM13yCGjmUgZZ2z3R31AxiG80fgEUxmofXLAKVOFAnFIJo9D09uuwcS63puwcD06WyYejffGzXCOrg-JcVXiTWerJHRYWtPb1kVF8tE2GI7IXm2agOPNPyIvN9fPk7v04en2fnL1kJYCoE-lNEYhVEoohhUtsM6LmlaxrowqGHCJJQpaQiUlGkBUjOOUy2wqMcei5iNyufbthukcqxKXGze683Zu_EK3xurfHWdf9az90DkUQmUyGpxtDHz7PmDo9dyGEpvGOGyHoBlAwSWHTET09A_61g7exfNWFGSyoHmk2JoqfRuCx3q7DFC9jEmvY9IxJr2KSS9FJz_P2Eq-QokAXwMhtmIE_nv2P7afv5ufKQ</recordid><startdate>20181008</startdate><enddate>20181008</enddate><creator>Romanenko, Svetlana A.</creator><creator>Serdyukova, Natalya A.</creator><creator>Perelman, Polina L.</creator><creator>Trifonov, Vladimir A.</creator><creator>Golenishchev, Feodor N.</creator><creator>Bulatova, Nina Sh</creator><creator>Stanyon, Roscoe</creator><creator>Graphodatsky, Alexander S.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7229-1092</orcidid><orcidid>https://orcid.org/0000-0002-0951-5209</orcidid></search><sort><creationdate>20181008</creationdate><title>Multiple intrasyntenic rearrangements and rapid speciation in voles</title><author>Romanenko, Svetlana A. ; Serdyukova, Natalya A. ; Perelman, Polina L. ; Trifonov, Vladimir A. ; Golenishchev, Feodor N. ; Bulatova, Nina Sh ; Stanyon, Roscoe ; Graphodatsky, Alexander S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c511t-88aa9e1d9592ed07ef67f0d2edda972138ece50c1d88ea1ee923eb384b8e6e7f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>13/106</topic><topic>14/32</topic><topic>14/34</topic><topic>14/63</topic><topic>38/77</topic><topic>631/181/2474</topic><topic>631/208/1405</topic><topic>Animals</topic><topic>Arvicolinae - genetics</topic><topic>Biogeography</topic><topic>Chromosome Painting</topic><topic>Chromosomes, Mammalian - genetics</topic><topic>DNA probes</topic><topic>Evolution, Molecular</topic><topic>Evolutionary conservation</topic><topic>Gene Rearrangement - genetics</topic><topic>Genetic Speciation</topic><topic>Genomes</topic><topic>Humanities and Social Sciences</topic><topic>Karyotypes</topic><topic>multidisciplinary</topic><topic>Phylogeny</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Speciation</topic><topic>Species</topic><topic>Synteny</topic><topic>Synteny - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Romanenko, Svetlana A.</creatorcontrib><creatorcontrib>Serdyukova, Natalya A.</creatorcontrib><creatorcontrib>Perelman, Polina L.</creatorcontrib><creatorcontrib>Trifonov, Vladimir A.</creatorcontrib><creatorcontrib>Golenishchev, Feodor N.</creatorcontrib><creatorcontrib>Bulatova, Nina Sh</creatorcontrib><creatorcontrib>Stanyon, Roscoe</creatorcontrib><creatorcontrib>Graphodatsky, Alexander S.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Science Journals</collection><collection>ProQuest Biological Science Journals</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Romanenko, Svetlana A.</au><au>Serdyukova, Natalya A.</au><au>Perelman, Polina L.</au><au>Trifonov, Vladimir A.</au><au>Golenishchev, Feodor N.</au><au>Bulatova, Nina Sh</au><au>Stanyon, Roscoe</au><au>Graphodatsky, Alexander S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multiple intrasyntenic rearrangements and rapid speciation in voles</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2018-10-08</date><risdate>2018</risdate><volume>8</volume><issue>1</issue><spage>14980</spage><epage>9</epage><pages>14980-9</pages><artnum>14980</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Remarkably stable genomic chromosome elements (evolutionary conserved segments or syntenies) are the basis of large-scale chromosome architecture in vertebrate species. However, these syntenic elements harbour evolutionary important changes through intrachromosomal rearrangements such as inversions and centromere repositioning. Here, using FISH with a set of 20 region-specific probes on a wide array of 28 species, we analyzed evolution of three conserved syntenic regions of the Arvicolinae ancestral karyotype. Inside these syntenies we uncovered multiple, previously cryptic intrachromosomal rearrangements. Although in each of the three conserved blocks we found inversions and centromere repositions, the blocks experienced different types of rearrangements. In two syntenies centromere repositioning predominated, while in the third region, paracentric inversions were more frequent, whereas pericentric inversions were not detected. We found that some of the intrachromosomal rearrangements, mainly paracentric inversions, were synapomorphic for whole arvicoline genera or tribes: genera
Alexandromys
and
Microtus
, tribes Ellobini and Myodini. We hypothesize that intrachromosomal rearrangements within conserved syntenic blocks are a major evolutionary force modulating genome architecture in species-rich and rapidly-evolving rodent taxa. Inversions and centromere repositioning may impact speciation and provide a potential link between genome evolution, speciation, and biogeography.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30297915</pmid><doi>10.1038/s41598-018-33300-6</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-7229-1092</orcidid><orcidid>https://orcid.org/0000-0002-0951-5209</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 2045-2322 |
ispartof | Scientific reports, 2018-10, Vol.8 (1), p.14980-9, Article 14980 |
issn | 2045-2322 2045-2322 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6175948 |
source | Open Access: PubMed Central; Publicly Available Content Database; Free Full-Text Journals in Chemistry; Springer Nature - nature.com Journals - Fully Open Access |
subjects | 13/106 14/32 14/34 14/63 38/77 631/181/2474 631/208/1405 Animals Arvicolinae - genetics Biogeography Chromosome Painting Chromosomes, Mammalian - genetics DNA probes Evolution, Molecular Evolutionary conservation Gene Rearrangement - genetics Genetic Speciation Genomes Humanities and Social Sciences Karyotypes multidisciplinary Phylogeny Science Science (multidisciplinary) Speciation Species Synteny Synteny - genetics |
title | Multiple intrasyntenic rearrangements and rapid speciation in voles |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T23%3A04%3A23IST&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=Multiple%20intrasyntenic%20rearrangements%20and%20rapid%20speciation%20in%20voles&rft.jtitle=Scientific%20reports&rft.au=Romanenko,%20Svetlana%20A.&rft.date=2018-10-08&rft.volume=8&rft.issue=1&rft.spage=14980&rft.epage=9&rft.pages=14980-9&rft.artnum=14980&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-018-33300-6&rft_dat=%3Cproquest_pubme%3E2117148706%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c511t-88aa9e1d9592ed07ef67f0d2edda972138ece50c1d88ea1ee923eb384b8e6e7f3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2117148706&rft_id=info:pmid/30297915&rfr_iscdi=true |