Indeed, kin recognition is closely linked with microbial cooperative behaviors (e.g., formation of multicellular aggregates, secretion of "public goods" that benefit the community and more). But how exactly does microbial kin recognition work-and what can it teach scientists about the evolution of life as we know it?
Why Do Organisms Cooperate? The Evolutionary Basis of Kin Recognition
From an evolutionary standpoint, cooperation is a bit of a puzzle. "In the general Darwinian framework, it's [about] survival of the fittest," said Daniel Wall, Ph.D., a professor of molecular biology at the University of Wyoming. The underlying message is "'I just want to compete, and if I'm the strongest, then I'm going to survive.' Cooperation seems to fly in the face of that." In other words, why would organisms put resources toward helping one another, sometimes to their own detriment?
The theory of kin selection posits that by helping its kin survive and reproduce, an organism still passes genes to the next generation, albeit indirectly (i.e., an organism's fitness is based on both its own ability to reproduce as well as that of its relatives). As such, the more closely related the organisms are (the more genes they share), the more likely cooperation will occur. Kin recognition ensures organisms target cooperative behaviors toward those with the same/similar genetic blueprint.
Cooperation also affords individuals capabilities they otherwise wouldn't have, which, in turn, increases their own fitness. For instance, in a school of fish, "the fish recognize that the other fish in the school are highly related to them, and they are able to move around [in unison]," Wall said. In doing so, "they're providing cooperative behaviors to the group," like defense against predation.
Kin Recognition and Microbial Cooperation
With that in mind, microbes engage in many cooperative behaviors where kin recognition is valuable. Wall pointed to myxobacteria, a group of predatory, soil-dwelling bacteria, and the focus of his lab, as a key example. During nutrient starvation, myxobacteria aggregate to form fruiting bodies-stalk-like, multicellular structures-that contain environmentally resistant spores. When conditions improve, the spores germinate into vegetative cells, thus ensuring survival of the population.
Myxobacteria cells "are typically in very complex environments that are made up of many different types of microbes, or even many different lineages of their own species that don't necessarily get along," Wall explained. To make a fruiting body, myxobacteria cells must determine who their siblings are amidst the microbial crowd. Moreover, only a fraction of myxobacteria in the fruiting body will survive-the rest (up to 80%) will die. "The cells are sort of making the ultimate sacrifice to provide nutrients for the other cells to go through the costly [fruiting body] developmental program," Wall said. Making this sacrifice is only worth it, in evolutionary terms, if the beneficiaries propagate traits of the sacrificial cells.
Along these lines, microbes perform a host of biological processes by secreting molecules involved in everything from defense to communication. For example, many bacteria secrete siderophores to scavenge iron-an element critical for microbial growth-from their environment. These public goods are costly to make, and "once [a] molecule leaves the cell, that cell has little control over it. So, any other cell in the population can use it," Wall noted. Kin recognition allows microbes to release public goods at times where they can be exploited by closely related organisms, rather than competitors.
How Do Microbes Recognize Their Kin?
Kin recognition is based on the genetic relatedness between organisms. When microbes reproduce asexually, progeny cells are genetically identical. However, in the environment there is often genetic variation in the larger population, such that neighboring cells are not necessarily clonal. Additionally, horizontal gene transfer is rampant in some ecological niches, and newly acquired social genes can alter the specificity of kin recognition. Often, changes to a single gene or set of genes changes microbial kin recognition. As such, "the key factors are the subset of genes involved in social interactions," Wall explained.
To that end, kin recognition in Myxococcus xanthus, a ubiquitous myxobacterium, depends on 2 surface receptors, TraA and TraB. TraA, the recognition determinant, is highly polymorphic-different isolates of M. xanthus often have different versions of TraA. "The sequence variability in TraA provides specificity," Wall said. For cells to recognize one another, they must have identical (or highly similar) versions of TraA. If a cell brushes up against its neighbor, and "the cell has the identical [TraA] allele, then that would indicate that it's highly related, and likely clonal [i.e., genetically identical, or nearly identical], because that cell is also in the same local environment," he explained.
If compatible, the receptors bind by homotypic interactions and the myxobacteria then engage in cooperative behaviors, like aggregation or outer membrane exchange (OME), a process in which the bacteria swap outer membrane proteins and lipids. Through OME, "1 cell can heal another cell from damage, [or] it can restore defective phenotypes by transferring proteins that another cell was missing," Wall noted, highlighting the process's altruistic nature.
Like the TraA system in myxobacteria, contact-dependent kin recognition also occurs in the urinary tract infection-inducing bacterium Proteus mirabilis, as well as other microbes like the social amoeba, Dictyostelium discoideum (slime mold) and Saccharomyces cerevisiae (brewer's yeast). Recognition can also occur via indirect mechanisms. Quorum sensing is an example-bacteria release signals called autoinducers that bind to the cognate receptor on other cells. As the bacteria reproduce, the signal gets more concentrated. Once it reaches a threshold, gene expression in a population changes, leading to a cooperative outcome. The process ensures microbes put energy and resources toward behaviors, like biofilm formation, virulence factor production and bioluminescence, among others, when it is most beneficial to the cooperating population.
Kin Discrimination: Kin Recognition's Other Half
Sometimes, it is less about recognizing organisms who are self-like and more about discriminating against those who are not. Indeed, microbes secrete compounds (e.g., bacteriocins) that benefit close kin by eliminating nonkin. For example, some strains of Escherichia coli secrete colicins, toxins that destroy bacterial cell membranes. Strains that produce colicins have an immunity protein that protects them from the toxin, while strains that do not harbor the immunity protein die. In a population of mixed strains, surviving cells are more likely to be related.
Similarly, for myxobacteria, 2 cells may have compatible TraA receptors and undergo OME, in which "they exchange hundreds of different proteins and lipids," Wall said. "In that collection, there's [also] a whole suite of polymorphic toxins. If the other cell is truly clonal then it's going to have the cognate immunity proteins to the suite of toxins that are being transferred, and that cell will be fine. But, if it's a cell that happened to have a compatible TraA allele, but it's not clonal, then there's going to be antagonism caused by the exchange of these toxins." This highlights how microbes often employ a 2-pronged approach, using mechanisms of both recognition and discrimination to find their kin.
Why is Studying Microbial Kin Recognition Important?
Investigating mechanisms of microbial kin recognition, discrimination and cooperation can lend important insights into the behavioral dynamics of microbial populations, including those related to human health, like the gut microbiota. However, Wall noted the benefits go beyond understanding the ins and outs of microbial interactions.
"[Kin] recognition in animals is a complex process," he said. "It generally involves the 5 senses and cognition. So, they have visual cues, they have smells, they have touch, etc." Because of this, trying to tease apart the molecular mechanisms of recognition "is just too complicated." Microbes are brainless and genetically simpler. They provide an experimentally tractable platform to identify the genetic and molecular underpinnings of kin recognition, which could inform scientists' understanding of the process on a broader scale.
Furthermore, Wall thinks learning about the cooperative outcomes of kin recognition, particularly in myxobacteria, can help address some fundamental questions in evolutionary biology. For example, "Why haven't bacteria developed complex multicellular life like the eukaryotes have?" he asked. "They're a lot more diverse, they've been around for a lot longer…there were obviously evolutionary hurdles to develop complex, multicellular life."
Myxobacteria, the only known prokaryotes to transition from a unicellular to multicellular lifestyle, offer a great starting place for answering this question. They "cobble together [related] cells from their environment to create a multicellular organism," he said. By comparing this aggregative approach of multicellularity to that of plants and animals (i.e., fertilization and continuous division and differentiation of an egg cell), Wall believes "we can better understand the evolutionary history of multicellular development."
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