Mussels and other bivalves have the largest and most diverse number of sensors for detecting pathogens in the entire animal kingdom. They act as real natural “signalers” against possible infections.
These are Toll-like receptors (TLRs). toll-like receptors), important components of the innate immune system of almost all animals.
Holger Motzkau / Wikimedia Commons, CC BY
The name comes from German losseswhich means incredible or fantastic. It was coined by biologist Christiane Nüsslein-Volhard in the 1980s when she discovered a key gene in the embryonic development of flies. Drosophila melanogaster. Jules Hoffmann later discovered that this gene was also critical for the immune defense of flies. When similar proteins responsible for pathogen recognition were identified in mammals, they were named Toll-like receptors due to its similarity to the Toll gene.
Invertebrates protect themselves from infections
Hoffmann’s discovery was an important milestone in biology. He broke with the traditional view that invertebrates lack developed immune mechanisms. In recognition of this pioneering work, Hoffmann was awarded the Nobel Prize in Physiology or Medicine in 2011, along with Bruce Beutler, who discovered the role of TLRs in mammalian innate immunity.
Their results opened a new era in the study of immunology, showing that the basic mechanisms of defense against pathogens are deeply conserved in the animal kingdom.
Defensive arsenal of bivalves
In vertebrates, including humans, the immune system can be divided into two groups: innate and adaptive, which are constantly in contact. The innate response, involving TLRs, is a rapid but nonspecific response, while the adaptive response is more specialized and produces specific antibodies for each pathogen.
TLR receptors are present in most metazoans (metazoans) and play a critical role in immunity. Its role is to identify pathogens, such as bacteria or viruses, and trigger the body’s immune response to fight the infection. However, not all animals have the same arsenal.
Bivalves such as mussels, which rely solely on their innate immune system and do not produce antibodies, have approximately 260 TLR genes. More than any other animal species. This allows them to recognize a large number of pathogens. By comparison, humans have 10 TLRs, but in return we have antibodies and other specific immune tools.
Wikimedia Commons, CC BY
This difference is very striking. First of all, when we compare them to other invertebrates that live in the same ecosystem and are also susceptible to potential infections. Sea urchins have many of these genes, but in much smaller quantities.
The above findings were obtained by our immunology and genomics group at the CSIC Institute of Marine Sciences and published in a study published in 2023. Molecular biology and evolution on the evolution of TLR genes in 85 species of the animal world.
Amazing Genetic Diversity
In other animals, including many invertebrates such as insects, TLR genes are concentrated in a single evolutionary group or clade. However, in mussels, 260 TLR genes are distributed among three major clades. This shows an unprecedented level of animal diversity.
Moreover, when comparing mussels with other metazoan species such as cnidarians (the group that includes jellyfish and corals), these animals were found to have much fewer TLRs. This puts bivalves in a unique evolutionary position.
Mussels Vs. vertebrates
In vertebrates, the adaptive immune system allows them to create specific antibodies to fight specific pathogens. This provides them with specific long-term stability. But bivalves lacking this ability have evolved an incredibly diverse innate immune response. This allows them to respond quickly and effectively to a wide range of threats, demonstrating an impressive evolutionary strategy.
This fact is critical because mussels and other bivalves live in marine environments where they constantly filter water laden with microorganisms, including pathogens. It is estimated that about 10 million viruses and 1 million bacteria can be found in just one milliliter of seawater. Not all of these microorganisms are harmful, but many are.
According to our findings, this diversity of TLR sensors lies not only in quantity, but also in functionality: they are specifically designed to recognize different types of viruses, bacteria and protozoa.
Pangenome, ideal for group protection
An additional discovery made by our research team in 2020 revealed something equally interesting: the mussel genome is an open pangenome. This means that as more individuals of a species are sequenced, new genes continue to be discovered.
Thus, genetic diversity is not yet fully understood, and each new sample may add more unique genes to a species’ genome. In a closed pangenome (like in humans), all possible genes of a species are already known and no new ones are expected.
Unlike vertebrates, in which variation between individual genomes is relatively small, in mussels a high percentage of genes, especially those related to immunity, have been observed to vary between individuals.
This means that different individuals in a colony may have different immune defenses, allowing the colony as a whole to be more resistant to environmental changes and pathogens.
In animals with an adaptive immune system, such as humans, variability between individuals is less important because the production of specific antibodies adapts to the pathogens they encounter. However, in bivalves, this genetic diversity is key to the species thriving in such a diverse and complex marine environment.
This genetic uniqueness not only makes them more resistant to marine pathogens, but also opens new questions about the evolution of immunity in different animal species. Bivalves, with their highly complex innate immune systems, demonstrate that there are many ways to survive in a world full of microbial threats.