Bivalves Present the Largest and Most Diversified Repertoire of Toll-Like Receptors in the Animal Kingdom, Suggesting Broad-Spectrum Pathogen Recognition in Marine Waters

Abstract

Toll-like receptors (TLRs) are the most widespread class of membrane-bound innate immune receptors, responsible of specific pathogen recognition and production of immune effectors though the activation of intracellular signaling cascades. The repertoire of TLRs was analyzed in 85 metazoans, enriched on molluscan species, an underrepresented phylum in previous studies. Following an ancient evolutionary origin, suggested by the presence of TLR genes in Anthozoa (Cnidaria), these receptors underwent multiple independent gene family expansions, the most significant of which occurred in bivalve molluscs. Marine mussels (Mytilus spp.) had the largest TLR repertoire in the animal kingdom, with evidence of several lineage-specific expanded TLR subfamilies with different degrees of orthology conservation within bivalves. Phylogenetic analyses revealed that bivalve TLR repertoires were more diversified than their counterparts in deuterostomes or ecdysozoans. The complex evolutionary history of TLRs, characterized by lineage-specific expansions and losses, along with episodic positive selection acting on the extracellular recognition domains, suggests that functional diversification might be a leading evolutionary force. We analyzed a comprehensive transcriptomic dataset from Mytilus galloprovincialis and built transcriptomic correlation clusters with the TLRs expressed in gills and in hemocytes. This evidenced the implication of specific TLRs in different immune pathways, as well as their specific modulation in response to different biotic and abiotic stimuli. We propose that, in a similar fashion to the remarkable functional specialization of vertebrate TLRs, the expansion of the TLR gene family in bivalves attends to a functional specification motivated by the biological particularities of these organisms and their living environment.

The brittle star genome illuminates the genetic basis of animal appendage regeneration

“…This observation ties in with the proposition that animal regeneration may recruit a homologous proliferating cell type (Lai and Aboobaker 2018;Srivastava 2021), a hypothesis that should be further explored with single-cell sequencing techniques and additional comparative analyses. The stronger conservation of gene expression during proliferation as opposed to the initial wound healing response is moreover consistent with the elevated turnover of immunity-related genes, broadly reported across animal lineages (Nei et al 1997;Leulier and Lemaitre 2008;Saco et al 2023) and which we also demonstrate here in echinoderms. Our results however contrast with the only previous study to have explicitly interrogated the conservation of animal regeneration gene expression programmes, which revealed a higher conservation of early response genes as opposed to the genes expressed during proliferation (Cary et al 2019).…”

“…This includes several enriched GO terms linked to immune-related processes (e.g. “response to other organisms”, “leukocyte migration”, “cell recognition”), which encompass genes known to display elevated gene birth and death rates in other animal lineages, such as Toll-Like Receptors (Nei et al 1997; Leulier and Lemaitre 2008; Saco et al 2023). Some GO term enrichments may reflect specific aspects of echinoderm biology.…”

Can evolutionary immunology decode micro and nanoplastic challenges?

“…This compelling evidence speaks in favor of using innate immune response as a focal point in understanding common and distinct mechanisms and pathways modulated by MNPs, and in identifying predictive cross-species biomarkers of MNP exposure. Nevertheless, PRRs, including TLRs, exhibit genetic diversity, and to find gene homology between different metazoan species is challenging (8)(9)(10). This divergence in homology may lead to distinct functions between species (8-10), a factor that needs consideration when employing a cross-species approach in assessing MNP-innate interactions.…”

The Role of the TLR4-MyD88 Signaling Pathway in the Immune Response of the Selected Scallop Strain “Hongmo No. 1” to Heat Stress

“…Besides the role of PRRs, TLRs also play a critical role in the production of immune effectors through the activation of intracellular signaling cascades [12]. According to an analysis of TLR repertoires in 85 metazoans, marine bivalves present the largest and most diversified repertoire of TLRs in the animal kingdom [13]. It was hypothesized that the expansion of the TLR gene family in mussels follows a functional diversity motivated by the biological features of these organisms and their habitats [13].…”

“…According to an analysis of TLR repertoires in 85 metazoans, marine bivalves present the largest and most diversified repertoire of TLRs in the animal kingdom [13]. It was hypothesized that the expansion of the TLR gene family in mussels follows a functional diversity motivated by the biological features of these organisms and their habitats [13]. This highlighted the role of TLRs in the innate immune system of bivalves.…”