Abstract
BackgroundToll-like receptors (TLRs) play a crucial role in immunity and development. They contain leucine-rich repeat domains, one transmembrane domain, and one Toll/IL-1 receptor domain. TLRs have been classified into V-type/scc and P-type/mcc TLRs, based on differences in the leucine-rich repeat domain region. Although TLRs are widespread in animals, detailed phylogenetic studies of this gene family are lacking. Here we aim to uncover TLR evolution by conducting a survey and a phylogenetic analysis in species across Bilateria. To discriminate between their role in development and immunity we furthermore analyzed stage-specific transcriptomes of the ecdysozoans Priapulus caudatus and Hypsibius exemplaris, and the spiralians Crassostrea gigas and Terebratalia transversa.ResultsWe detected a low number of TLRs in ecdysozoan species, and multiple independent radiations within the Spiralia. V-type/scc and P-type/mcc type-receptors are present in cnidarians, protostomes and deuterostomes, and therefore they emerged early in TLR evolution, followed by a loss in xenacoelomorphs. Our phylogenetic analysis shows that TLRs cluster into three major clades: clade α is present in cnidarians, ecdysozoans, and spiralians; clade β in deuterostomes, ecdysozoans, and spiralians; and clade γ is only found in spiralians. Our stage-specific transcriptome and in situ hybridization analyses show that TLRs are expressed during development in all species analyzed, which indicates a broad role of TLRs during animal development.ConclusionsOur findings suggest that a clade α TLR gene (TLR-Ca) and a clade β/γ TLR gene (TLR-Cβ/γ) were already present in the cnidarian-bilaterian common ancestor. However, although TLR-Ca was conserved in cnidarians, TLR-Cβ/γ was lost during the early evolution of these taxa. Moreover, TLR-Cβ/γ duplicated to generate TLR-Cβ and TLR-Cγ in the lineage to the last common protostome-deuterostome ancestor. TLR-Ca, TLR-Cβ and TLR-Cγ further expanded generating the three major TLR clades. While all three clades radiated in several spiralian lineages, specific TLRs clades have been presumably lost in other lineages. Furthermore, the expression of the majority of these genes during protostome ontogeny suggests a likely role in development.
Highlights
Toll-like receptors (TLRs) play a crucial role in immunity and development
We would like to mention the limitation of our method, as when performing transcriptomic surveys some TLRs could have been under-detected due to no expression in the tissue or the developmental stage sequenced, or because partial sequences obtained from transcriptomes could have been misclassified into TLR-like when an leucine-rich repeat (LRR) domain, the transmembrane domain and the Toll/IL-1 receptor (TIR) domain were not present together in one sequence
Based on our data we propose a scenario in which a Clade α type TLR gene (TLR-Cα) and a Clade β type TLR gene (TLR-Cβ)/γ were present in the planulozoan common ancestor
Summary
Toll-like receptors (TLRs) play a crucial role in immunity and development. We aim to uncover TLR evolution by conducting a survey and a phylogenetic analysis in species across Bilateria. To discriminate between their role in development and immunity we analyzed stage-specific transcriptomes of the ecdysozoans Priapulus caudatus and Hypsibius exemplaris, and the spiralians Crassostrea gigas and Terebratalia transversa. Toll-like receptors (TLRs) are involved in immunity and development in metazoans [1,2,3,4,5,6,7]. The first described TLR was the Drosophila gene Toll, which plays a role during early embryonic development [8, 9] and in immunity [10]. TLRs are involved in nervous system development in mice [44,45,46,47], the ligands that activate them during this process remain unknown [2]
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