Gene Loss

Publication Details

Identifier: JB_N2K3ZC

Curator: Raul Valente

Title:

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

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.

Last update:

07-05-2024

Associated Glosses (23 results)

GlossID	Species	Symbol	Gene Loss Mechanism	Loss Type	Lineage Specific	Citation
GL_H3T9RU	Inia geoffrensis	TLR5	LOF (frameshift, premature stop, ss)	Full	Iniidae	10.1093/molbev/msaa058
GL_ILUI34	Manis pentadactyla	TLR5	Gene deletion	Full	Pholidota	10.1093/molbev/msaa058
GL_IUETRH	Lipotes vexillifer	Tlr11	Gene deletion	Full	Lipotidae	10.1093/molbev/msaa058
GL_JXJRR0	Lipotes vexillifer	TLR5	LOF (frameshift, premature stop, ss)	Full	Lipotidae	10.1093/molbev/msaa058
GL_LMN9TY	Manis javanica	TLR5	Gene deletion	Full	Pholidota	10.1093/molbev/msaa058
GL_LSDI8N	Cavia aperea	TLR5	LOF (frameshift, premature stop, ss)	Full	Cavia	10.1093/molbev/msaa058
GL_OOEBZI	Leptonychotes weddellii	Tlr11	Exon(s) deletion	Full	Phocidae	10.1093/molbev/msaa058
GL_PAF0PP	Cavia tschudii	Tlr11	Gene deletion	Full	Cavia	10.1093/molbev/msaa058
GL_QVWGRF	Pontoporia blainvillei	TLR5	LOF (frameshift, premature stop, ss)	Full	Pontoporiidae	10.1093/molbev/msaa058
GL_R6ILZO	Arctocephalus pusillus	TLR5	LOF (frameshift, premature stop, ss)	Full	Otariidae	10.1093/molbev/msaa058