Distinct evolution of toll-like receptor signaling pathway genes in cetaceans.
Cetaceans
Ligand responsiveness
Molecular evolution
Positive selection
TLR4
Toll-like receptor signaling pathway
Journal
Genes & genomics
ISSN: 2092-9293
Titre abrégé: Genes Genomics
Pays: Korea (South)
ID NLM: 101481027
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
04
06
2019
accepted:
19
08
2019
pubmed:
20
9
2019
medline:
31
3
2020
entrez:
20
9
2019
Statut:
ppublish
Résumé
The relatively rapid spread and diversity of marine pathogens posed an initial and ongoing challenge for cetaceans (whales, dolphins, and porpoises), descendants of terrestrial mammals that transitioned from land to sea approximately 56 million years ago. Toll-like receptors (TLRs) play important roles in regulating immunity against pathogen infections by detecting specific molecular patterns and activating a wide range of downstream signaling pathways. The ever-increasing catalogue of mammalian genomes offers unprecedented opportunities to reveal genetic changes associated with evolutionary and ecological processes. This study aimed to explore the molecular evolution of TLR signaling pathway genes in cetaceans. Genes involved in the TLR signaling pathway were retrieved by BLAST searches using human coding sequences as queries. We tested each gene for positive selection along the cetacean branches using PAML and Hyphy. Physicochemical property changes of amino acids at all positively selected residues were assessed by TreeSAAP and visualized with WebLogo. Bovine and dolphin TLR4 was assessed using human embryonic kidney cell line HEK293, which lacks TLR4 and its co-receptor MD-2. We demonstrate that eight TLR signaling pathway genes are under positive selection in cetaceans. These include key genes in the response to Gram-negative bacteria: TLR4, CD14, and LY96 (MD-2). Moreover, 41 out of 65 positively selected sites were inferred to harbor substitution that dramatically changes the physicochemical properties of amino acids, with most of them situated in or adjacent to functional regions. We also found strong evidence that positive selection occurred in the lineage of the Yangtze finless porpoise, likely reflecting relatively recent adaptions to a freshwater milieu. Species-specific differences in TLR4 response were observed between cetacean and terrestrial species. Cetacean TLR4 was significantly less responsive to lipopolysaccharides from a terrestrial E. coli strain, possibly a reflection of the arms race of host-pathogen co-evolution faced by cetaceans in an aquatic environment. This study provides further impetus for studies on the evolution and function of the cetacean immune system.
Sections du résumé
BACKGROUND
The relatively rapid spread and diversity of marine pathogens posed an initial and ongoing challenge for cetaceans (whales, dolphins, and porpoises), descendants of terrestrial mammals that transitioned from land to sea approximately 56 million years ago. Toll-like receptors (TLRs) play important roles in regulating immunity against pathogen infections by detecting specific molecular patterns and activating a wide range of downstream signaling pathways. The ever-increasing catalogue of mammalian genomes offers unprecedented opportunities to reveal genetic changes associated with evolutionary and ecological processes.
OBJECTIVE
This study aimed to explore the molecular evolution of TLR signaling pathway genes in cetaceans.
METHODS
Genes involved in the TLR signaling pathway were retrieved by BLAST searches using human coding sequences as queries. We tested each gene for positive selection along the cetacean branches using PAML and Hyphy. Physicochemical property changes of amino acids at all positively selected residues were assessed by TreeSAAP and visualized with WebLogo. Bovine and dolphin TLR4 was assessed using human embryonic kidney cell line HEK293, which lacks TLR4 and its co-receptor MD-2.
RESULTS
We demonstrate that eight TLR signaling pathway genes are under positive selection in cetaceans. These include key genes in the response to Gram-negative bacteria: TLR4, CD14, and LY96 (MD-2). Moreover, 41 out of 65 positively selected sites were inferred to harbor substitution that dramatically changes the physicochemical properties of amino acids, with most of them situated in or adjacent to functional regions. We also found strong evidence that positive selection occurred in the lineage of the Yangtze finless porpoise, likely reflecting relatively recent adaptions to a freshwater milieu. Species-specific differences in TLR4 response were observed between cetacean and terrestrial species. Cetacean TLR4 was significantly less responsive to lipopolysaccharides from a terrestrial E. coli strain, possibly a reflection of the arms race of host-pathogen co-evolution faced by cetaceans in an aquatic environment.
CONCLUSION
This study provides further impetus for studies on the evolution and function of the cetacean immune system.
Identifiants
pubmed: 31535317
doi: 10.1007/s13258-019-00861-3
pii: 10.1007/s13258-019-00861-3
doi:
Substances chimiques
Toll-Like Receptors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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