Santiago de Compostela, Spain – The Consejo Superior de Investigaciones Científicas (CSIC), through the Immunology and Genomics group at the Marine Research Institute (IIM), has made a groundbreaking discovery in marine immunology: the identification of a massive expansion of Toll-like receptor (TLR) immune genes in mussels and other bivalve species.
The details of the research, conducted in collaboration with the University of Trieste (Italy), are published in the article “Bivalves Present the Largest and Most Diversified Repertoire of Toll-Like Receptors in the Animal Kingdom, Suggesting Broad-Spectrum Pathogen Recognition in Marine Waters” in the evolutionary journal Molecular Biology and Evolution.
Understanding the Immune Defense of Marine Mussels
Toll-like receptors (TLRs), crucial players in innate immune responses, have been widely studied in vertebrates. However, their evolutionary history and functional diversification in invertebrates remain relatively unexplored. The recent study delved into the TLR repertoire of 85 metazoans, with a particular focus on mollusk species, especially marine mussels (Mytilus spp.).
The findings revealed a surprising evolutionary expansion of TLRs in bivalve mollusks. This expansion was most pronounced in marine mussels, which possess the largest TLR repertoire in the animal kingdom. This suggests that bivalves have developed a more complex and sophisticated immune defense system compared to other invertebrates.
“This is something never seen before in the animal kingdom and highlights how evolution has equipped mussels and other bivalves with a unique ability to adapt and survive in hostile environments. Their genetic diversity in immune receptors is not only impressive but also raises fascinating questions about how other organisms might benefit from similar mechanisms,” says the lead researcher of the project, Antonio Figueras.
Functional Diversification
TLRs are present in nearly all animal species and play a critical role in defending organisms. They are responsible for recognizing pathogens and triggering the immune response.
Phylogenetic analyses showed that the TLR repertoires of bivalves are more diversified than those of deuterostomes or ecdysozoans. This diversification is likely due to lineage-specific expansions and losses, as well as positive selection acting on the extracellular recognition domains. These evolutionary forces suggest that functional diversification has played a key role in the evolution of TLRs in bivalves.
“What makes bivalves so fascinating is that, unlike vertebrates, they lack an adaptive immune system. Instead of producing specific antibodies, these animals rely exclusively on their innate immune system to defend against invaders. This is where the extraordinary diversity of TLRs discovered in these mollusks comes into play. Mussels, for example, have around 260 TLR genes in their genome, compared to just 10 in humans. Other bivalve species, such as oysters and clams, have around 100. This diversity allows bivalves to recognize a wider range of pathogens, a key factor for their survival in marine environments full of potentially dangerous microorganisms,” explains Amaro Saco, the first author of the article.
Immune Pathway Implications
To understand the functional implications of the expanded TLR repertoire in marine mussels, the study analyzed transcriptomic data from Mytilus galloprovincialis. This analysis revealed the involvement of specific TLRs in different immune pathways and their modulation in response to various biotic and abiotic stimuli.
“One of the most remarkable aspects of this discovery is how mussels, despite not having the ability to produce antibodies like humans, have developed a highly specific immune system. Thanks to their genetic variability, mussel populations can better adapt to different environments and pathogens. This study even suggests that mussels may have an evolutionary advantage over other species due to this genomic plasticity,” adds Antonio Figueras.
In fact, in 2020, the same team of researchers published the mussel genome, revealing that it has the first open “pan-genome” described in an animal. This means that mussels have a significant percentage of variable genes, present in some individuals and absent in others, most of them related to immunity. This mechanism of genetic variation among individuals strengthens the species’ resilience, allowing populations to collectively cope with environmental threats.
A Remarkable Adaptation
The study that provided this information traced the origin of TLR genes back to cnidarians, a group of marine animals such as jellyfish.
According to the study, the expansion of the TLR gene family in bivalves is likely the result of functional specialization driven by the unique biological characteristics of these organisms and their marine environment. This adaptation enables bivalves to effectively combat a wide range of pathogens and environmental stressors.
“Although these organisms have a small number of TLRs, bivalves have experienced a spectacular evolutionary expansion in this gene family. This expansion is accompanied by great functional diversity, allowing them to recognize and combat a wide range of pathogens,” notes Beatriz Novoa, the director of the research group.
The research team discovered that this diversity is not random but is driven by natural selection forces acting on the extracellular region of the TLRs, which directly interacts with pathogens. This detail suggests that evolution has shaped these genes to adapt to the specific threats faced by bivalves.
Future Directions
Future research on bivalve TLRs could provide valuable insights into the evolution of innate immunity and the development of new therapeutic strategies. Understanding the specific functions of individual TLRs in these organisms could lead to the development of targeted interventions for aquaculture and marine conservation.
Contact
Antonio Figueras
Institute of Marine Research (IIM), National Research Council (CSIC), Vigo, Spain
E-mail: antoniofigueras@iim.csic.es.
Reference (open access)
Amaro Saco, Beatriz Novoa, Samuele Greco, Marco Gerdol, Antonio Figueras, Bivalves Present the Largest and Most Diversified Repertoire of Toll-Like Receptors in the Animal Kingdom, Suggesting Broad-Spectrum Pathogen Recognition in Marine Waters, Molecular Biology and Evolution, Volume 40, Issue 6, June 2023, msad133, https://doi.org/10.1093/molbev/msad133
