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Evolution of toll-like receptors in the context of terrestrial ungulates and cetaceans diversification

BACKGROUND: Toll-like receptors (TLRs) are the frontline actors in the innate immune response to various pathogens and are expected to be targets of natural selection in species adapted to habitats with contrasting pathogen burdens. The recent publication of genome sequences of giraffe and okapi tog...

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Autores principales: Ishengoma, Edson, Agaba, Morris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314619/
https://www.ncbi.nlm.nih.gov/pubmed/28209121
http://dx.doi.org/10.1186/s12862-017-0901-7
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author Ishengoma, Edson
Agaba, Morris
author_facet Ishengoma, Edson
Agaba, Morris
author_sort Ishengoma, Edson
collection PubMed
description BACKGROUND: Toll-like receptors (TLRs) are the frontline actors in the innate immune response to various pathogens and are expected to be targets of natural selection in species adapted to habitats with contrasting pathogen burdens. The recent publication of genome sequences of giraffe and okapi together afforded the opportunity to examine the evolution of selected TLRs in broad range of terrestrial ungulates and cetaceans during their complex habitat diversification. Through direct sequence comparisons and standard evolutionary approaches, the extent of nucleotide and protein sequence diversity in seven Toll-like receptors (TLR2, TLR3, TLR4, TLR5, TLR7, TLR9 and TLR10) between giraffe and closely related species was determined. In addition, comparison of the patterning of key TLR motifs and domains between giraffe and related species was performed. The quantification of selection pressure and divergence on TLRs among terrestrial ungulates and cetaceans was also performed. RESULTS: Sequence analysis shows that giraffe has 94–99% nucleotide identity with okapi and cattle for all TLRs analyzed. Variations in the number of Leucine-rich repeats were observed in some of TLRs between giraffe, okapi and cattle. Patterning of key TLR domains did not reveal any significant differences in the domain architecture among giraffe, okapi and cattle. Molecular evolutionary analysis for selection pressure identifies positive selection on key sites for all TLRs examined suggesting that pervasive evolutionary pressure has taken place during the evolution of terrestrial ungulates and cetaceans. Analysis of positively selected sites showed some site to be part of Leucine-rich motifs suggesting functional relevance in species-specific recognition of pathogen associated molecular patterns. Notably, clade analysis reveals significant selection divergence between terrestrial ungulates and cetaceans in viral sensing TLR3. Mapping of giraffe TLR3 key substitutions to the structure of the receptor indicates that at least one of giraffe altered sites coincides with TLR3 residue known to play a critical role in receptor signaling activity. CONCLUSION: There is overall structural conservation in TLRs among giraffe, okapi and cattle indicating that the mechanism for innate immune response utilizing TLR pathways may not have changed very much during the evolution of these species. However, a broader phylogenetic analysis revealed signatures of adaptive evolution among terrestrial ungulates and cetaceans, including the observed selection divergence in TLR3. This suggests that long term ecological dynamics has led to species-specific innovation and functional variation in the mechanisms mediating innate immunity in terrestrial ungulates and cetaceans. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12862-017-0901-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-53146192017-02-24 Evolution of toll-like receptors in the context of terrestrial ungulates and cetaceans diversification Ishengoma, Edson Agaba, Morris BMC Evol Biol Research Article BACKGROUND: Toll-like receptors (TLRs) are the frontline actors in the innate immune response to various pathogens and are expected to be targets of natural selection in species adapted to habitats with contrasting pathogen burdens. The recent publication of genome sequences of giraffe and okapi together afforded the opportunity to examine the evolution of selected TLRs in broad range of terrestrial ungulates and cetaceans during their complex habitat diversification. Through direct sequence comparisons and standard evolutionary approaches, the extent of nucleotide and protein sequence diversity in seven Toll-like receptors (TLR2, TLR3, TLR4, TLR5, TLR7, TLR9 and TLR10) between giraffe and closely related species was determined. In addition, comparison of the patterning of key TLR motifs and domains between giraffe and related species was performed. The quantification of selection pressure and divergence on TLRs among terrestrial ungulates and cetaceans was also performed. RESULTS: Sequence analysis shows that giraffe has 94–99% nucleotide identity with okapi and cattle for all TLRs analyzed. Variations in the number of Leucine-rich repeats were observed in some of TLRs between giraffe, okapi and cattle. Patterning of key TLR domains did not reveal any significant differences in the domain architecture among giraffe, okapi and cattle. Molecular evolutionary analysis for selection pressure identifies positive selection on key sites for all TLRs examined suggesting that pervasive evolutionary pressure has taken place during the evolution of terrestrial ungulates and cetaceans. Analysis of positively selected sites showed some site to be part of Leucine-rich motifs suggesting functional relevance in species-specific recognition of pathogen associated molecular patterns. Notably, clade analysis reveals significant selection divergence between terrestrial ungulates and cetaceans in viral sensing TLR3. Mapping of giraffe TLR3 key substitutions to the structure of the receptor indicates that at least one of giraffe altered sites coincides with TLR3 residue known to play a critical role in receptor signaling activity. CONCLUSION: There is overall structural conservation in TLRs among giraffe, okapi and cattle indicating that the mechanism for innate immune response utilizing TLR pathways may not have changed very much during the evolution of these species. However, a broader phylogenetic analysis revealed signatures of adaptive evolution among terrestrial ungulates and cetaceans, including the observed selection divergence in TLR3. This suggests that long term ecological dynamics has led to species-specific innovation and functional variation in the mechanisms mediating innate immunity in terrestrial ungulates and cetaceans. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12862-017-0901-7) contains supplementary material, which is available to authorized users. BioMed Central 2017-02-16 /pmc/articles/PMC5314619/ /pubmed/28209121 http://dx.doi.org/10.1186/s12862-017-0901-7 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Ishengoma, Edson
Agaba, Morris
Evolution of toll-like receptors in the context of terrestrial ungulates and cetaceans diversification
title Evolution of toll-like receptors in the context of terrestrial ungulates and cetaceans diversification
title_full Evolution of toll-like receptors in the context of terrestrial ungulates and cetaceans diversification
title_fullStr Evolution of toll-like receptors in the context of terrestrial ungulates and cetaceans diversification
title_full_unstemmed Evolution of toll-like receptors in the context of terrestrial ungulates and cetaceans diversification
title_short Evolution of toll-like receptors in the context of terrestrial ungulates and cetaceans diversification
title_sort evolution of toll-like receptors in the context of terrestrial ungulates and cetaceans diversification
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314619/
https://www.ncbi.nlm.nih.gov/pubmed/28209121
http://dx.doi.org/10.1186/s12862-017-0901-7
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