Convergent Losses of TLR5 Suggest Altered Extracellular Flagellin Detection in Four Mammalian Lineages.

Molecular Biology and Evolution
Virag SharmaMichael Hiller

Abstract

Toll-like receptors (TLRs) play an important role for the innate immune system by detecting pathogen-associated molecular patterns. TLR5 encodes the major extracellular receptor for bacterial flagellin and frequently evolves under positive selection, consistent with coevolutionary arms races between the host and pathogens. Furthermore, TLR5 is inactivated in several vertebrates and a TLR5 stop codon polymorphism is widespread in human populations. Here, we analyzed the genomes of 120 mammals and discovered that TLR5 is convergently lost in four independent lineages, comprising guinea pigs, Yangtze river dolphin, pinnipeds, and pangolins. Validated inactivating mutations, absence of protein-coding transcript expression, and relaxed selection on the TLR5 remnants confirm these losses. PCR analysis further confirmed the loss of TLR5 in the pinniped stem lineage. Finally, we show that TLR11, encoding a second extracellular flagellin receptor, is also absent in these four lineages. Independent losses of TLR5 and TLR11 suggest that a major pathway for detecting flagellated bacteria is not essential for different mammals and predicts an impaired capacity to sense extracellular flagellin.

References

Aug 8, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·A T GewirtzJ L Madara
Apr 19, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·Yimin YuAndrew T Gewirtz
Apr 25, 2003·The Journal of Biological Chemistry·Steven B MizelRoy R Hantgan
Sep 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·W James KentDavid Haussler
Jul 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·Thomas R HawnAlan Aderem
Jan 28, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Andrew T GewirtzJudy H Cho
Aug 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Vincent FeuilletLena Alexopoulou
Nov 8, 2007·Nature Genetics·Timothy B SacktonAndrew G Clark
Nov 17, 2007·The Journal of Clinical Investigation·Matam Vijay-KumarAndrew T Gewirtz
Dec 11, 2007·Seminars in Immunopathology·Matam Vijay-KumarAndrew T Gewirtz
Jan 31, 2009·Molecular Biology and Evolution·Gabriela WlasiukMichael W Nachman
Jan 30, 2010·Bioinformatics·Aaron R Quinlan, Ira M Hall
Mar 6, 2010·Science·Matam Vijay-KumarAndrew T Gewirtz
Jul 20, 2010·Bioinformatics·W J KentD Karolchik
Jan 7, 2011·Genome Research·Szymon M KiełbasaMartin C Frith
Jan 18, 2011·Molecular Biology and Evolution·Miguel Alcaide, Scott V Edwards
Apr 27, 2011·BMC Evolutionary Biology·Jonathan H GeislerJohn Gatesy
Oct 20, 2011·Nucleic Acids Research·Yuichi KodamaUNKNOWN International Nucleotide Sequence Database Collaboration
Dec 22, 2011·BMC Evolutionary Biology·Helena ArealPedro J Esteves
Jul 26, 2012·BMC Evolutionary Biology·Sarah A SmithRichard D Emes
Sep 8, 2012·Genome Research·Jennifer HarrowTim J Hubbard
Sep 15, 2012·Current Biology : CB·Daniel Okin, Ruslan Medzhitov
Oct 30, 2012·Cell·Ramkumar MathurSankar Ghosh
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Mar 1, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·T Eoin WestShawn J Skerrett
Mar 5, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nasser M Al-DaghriManuela Sironi
Oct 15, 2013·Molecular Ecology·Frédéric DelsucRob Knight
Mar 13, 2014·Developmental and Comparative Immunology·Hana BainováMichal Vinkler
Nov 13, 2014·Genetics, Selection, Evolution : GSE·Michal VinklerJosef Bryja
Dec 20, 2014·Cold Spring Harbor Perspectives in Medicine·Simon ClarkAnn Williams
Dec 30, 2014·Molecular Biology and Evolution·Joel O WertheimKonrad Scheffler
Feb 14, 2015·Aging Cell·Alexey A FushanVadim N Gladyshev
Jan 8, 2016·Scientific Reports·Carlos G P VoogdtJos P M van Putten
Apr 2, 2016·Science·David GordonEvan E Eichler
Apr 19, 2016·Nature Reviews. Genetics·Ricard Albalat, Cristian Cañestro

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