Need A Helping Hand? Just Infect A Stranger With A Cooperative Gene
    By Catarina Amorim | November 11th 2009 08:27 PM | 7 comments | Print | E-mail | Track Comments
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    After many years as a scientist (immunology) at Oxford University I moved into scientific journalism and public understanding of science. I am...

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    Cooperation is seen in every corner of life from microbes to humans, many times with no obvious advantages to those that provide it at high costs. Given the existence of “freeloading cheaters” ready to exploit the resources of those cooperating, why is it that cooperation persist? In an article now published in the journal Current Biology Nogueira and colleagues suggest that in bacteria this can result from highly mobile genes that “jump” from one cell to the next carrying the cooperative traits, effectively turning everyone into a cooperator. They also show that, at least in Escherichia coli (E. coli), this new population remains stable through “punisher” genes that impose a mafia-like strategy of “cooperation or death”, ensuring that the new cooperators do not revert to freeloading. The work – by shedding some light on the complex interactions of microbes that ultimately determine which bacteria thrive or disappear – can have important implications for both human health and economy.

    Electron miscrope photo E. coliScientists now agree that cooperation thrives if it benefits the cooperator or/and its relatives. The logic behind this last behaviour resides in the fact that to benefit relatives - which are genetically very similar to the cooperator - is to increase the probability that shared genes, including the cooperative traits, will pass to the next generation. Natural selection that preserves cooperative behaviours benefiting relatives - sometimes even at a cost to the cooperator’s survival and/or reproduction – is called kin selection. Classic examples of kin selection in action are “watchers” - individuals that, at the expense of their own security, guard and raise the alarm in the community - or the sterile workers found in ants and honey bees colonies. So cooperation is affected not only by its costs and benefits, but also by the genetic similarity between cooperator and those benefiting from the behaviour, with higher relatedness increasing the probability of cooperation occur.

    Following this idea Teresa Nogueira (Centre for Environmental Biology, Univ. Lisbon, and Superior School of Health Technology of Oporto, Portugal), Eduardo P.C. Rocha and colleagues, at the Institute Pasteur and the UPMC Univ. Paris 06 (Paris, France) while trying to understand cooperation among bacteria wondered if horizontal gene transfer - a non-sexual process, very common in bacteria, where genes “jump” from one individual to another – by increasing the genetic similarity between “infected” individuals, could lead to cooperation via kin selection. Using mathematical tools and adding the effect of horizontal gene transfer to costs, benefits and genetic similarity the researchers confirmed that – theoretically at least – highly mobile genes carrying cooperative traits should promote cooperation, which is then be maintained by kin selection.

    To confirm this hypothesis Nogueira and colleagues looked at E.coli, which is an abundant microorganism in the human gut flora, where the bacteria typically live in a mutually beneficial relationship with humans. However, changes in its social interactions with other microbes and/or the human host can turn E. coli into an extremely virulent organism, making it a particular interesting subject for this study. Not only that, but many of E. coli vital functions depend on secreted proteins (the so called secretome) that are easily exploited by other microbes, turning E. coli into a potential “collaborator”, even if an unintentional one.

    The work now published analyses 21 E. coli genomes and their secretome genes and starts by finding that only a very small percentage of them are part of the “core genome” – those genes shared by all the strains of the species so, supposedly, those linked to functions crucial for survival – what agrees with the idea that the secretome contains cooperative traits, since, by definition, cooperative genes can be easily lost by natural selection.

    Next Nogueira and colleagues try to identify the proteins of the secretome by comparing them to a large known sample from the human gut. And in fact, several of them were potential cooperative traits but, and even more interesting, they also found many E. coli secretome genes in other bacteria. This agrees with Nogueira’s prediction that cooperative traits accumulate in highly mobile genes that, by “moving around”, increase the genetic similarity of previously unrelated bacteria (in this case, even across species). This conclusion was further supported by the fact that large part of the secretome was found to be coded by a piece of extra-chromosomal DNA called plasmid, which is, simply, the most mobile part of the whole bacterial genome

    Finally, secreted proteins are costly as they are not recycled and - if Nogueira’s hypothesis was correct - as cooperative traits liable to be exploited by cheaters, they should be under intense selection pressure. And indeed the secretome was found to comprise the proteins least expensive to produce in the entire organism, consistent with cooperation costs.

    A last question remained - if highly mobile cooperative genes, by jumping between individuals, turn everyone into a cooperator, in the same way their mobility should lead them to be easily lost, creating, yet again, a new freeloading population. So how is this avoided? One way would be by imposing punishments and this possibility led Nogueira and colleagues to search for proteins known to stabilize gene integration by “punishing” the organism if the gene is lost.

    And indeed they found two such mechanisms - the “Restriction Modification” and the “Bacterial Toxin–Antitoxin” system. Both systems work as a complex of two genes where one provokes the death of the host if the other goes missing. In E. coli these systems were found next to the secretome genes suggesting that the stability of the new cooperator population is maintained by making the cost of losing the cooperative trait higher then the benefit of becoming a freeloader.

    In conclusion, Nogueira and colleagues’ work showed that the secreted proteins of E. coli behave as cooperative traits - they are part of the “disposable” part of the genome, show signs of intense selective pressure and some were even identified as potential cooperative traits. In agreement with the researchers’ model most of the genes coding for the secretome are located in the highest mobile part of the bacterial genome and found to be shared by other bacteria. This last increased genetic similarity allows the cooperative traits to stay in the population through kin selection, while “punisher” genes further assure the stability of the new population via a “cooperate or die” policy.

    These results strongly suggests that - like Nogueira proposed - cooperation among bacteria can be enforced by extremely mobile genes containing the cooperative traits that jumping between individuals turn them into cooperators. This new population is then maintained by kin selection and punishment.

    Microbes are used in a variety of jobs important for humans, from cleaning petroleum oil of the oceans or wastage treatment to food growth, and, of course, they are crucial agents of disease and health. They are also extremely social organisms normally living in a mix of many different species - the flora of the human gut is a good example – with different populations growing more or less in result of the social interaction between them and/or the host. Nogueira, Rocha and colleagues’ work is an important step in the understanding of these complex relationships and might contribute one day for better ways of manipulating bacterial growth, whether with the intention of stopping pathogenic populations or to stimulate beneficial ones. In the specific case of E. coli this knowledge is particularly important as many of its cooperative traits are virulence factors and responsible for turning this normally innocuous bacteria into a life-threatening dangerous pathogen.


    Steve Davis
    Thanks for a fascinating article. But the thing that amazes me is how these researchers could turn a wonderful discovery into some grubby explanation based on kin selection. None of the research led to kin selection as an explanation, it was introduced as a pre-conceived notion.
    Gerhard Adam
    Classic examples of kin selection in action are “watchers” - individuals that, at the expense of their own security, guard and raise the alarm in the community - or the sterile workers found in ants and honey bees colonies.
    Unfortunately this simply isn't true.  In effect, the problem of kin selection is that it fails to distinguish between nestmate recognition versus genetic kin and invariably seems like it is based on coincidence rather than predictable events. 
    Thus, the level of aggression between workers strongly depends on whether they are from the same supercolony, but not on their overall genetic dissimilarity.
    There is no doubt that kinship can make a difference, but it is quite difficult to conclude that there is any genetic basis for recognition beyond the familiarity of being raised in the same group together.

    More importantly, the concepts of "kin" are presumed to mean offspring and are focused on the behavior of the organism, and yet we have to consider that at the cellular level there are also relationships that need to be maintained.  The "altruistic" sacrifice of white blood cells, way well be interpreted as being a defense by which "kin" (i.e. all the related cells in a multicellular organism) are protected by the actions of a few designated cells.

    However, it could also be argued that this is a variation of group selection whereby an altruistic action benefits the group without necessarily benefiting the individual.  While this seems to go contrary to the perceived function of evolution, it doesn't violate any of its principles if there is no meaningful existence for an individual without the group.

    In other words, an individual can evolve to become dependent on a group which in turn creates a different set of selection pressures such that individual existence and survival is no longer a viable option.  This would have little to do with kin, and instead shift to group selection as the primary survival need.  In this case, it makes no sense to talk about "individual benefit", since there is none without the group.  There is no survival benefit to isolated worker ants or soldiers, therefore there doesn't have to be any kin selection to recognize that it is the survival of the nest that is important and not the individual.

    Similarly a huge driving force that will create selection pressures in this direction is the amount of energy necessary to maintain segregation and competition.  If the energy costs are too high (i.e. calories), then it is obviously more beneficial to simply tolerate others than it is to expend your resources in a battle that can't be won.

    In effect, it's the biological cost/benefit analysis that determines cooperation and the degree to which it exists and not some arbitrary notion of a gene wanting to propagate into the future.  Genes that express such traits will tend to have a greater representation in future generations because it has a lower cost energy and ensures a higher likelihood of fitness.

    At the levels of single celled organisms, then such expressions would occur as indicated by game theory and there is no problem of "punishers" or "cooperative" genes, but it makes no sense to introduce kinship to explain it.  Once again, it is the colony that is important and this is also demonstrated by the fact that bacterial cannibalism occurs when that colony becomes stressed.  But that cannibalism doesn't result in the destruction of the entire colony, but is of a limited sort that ensures that it isn't simply a "free-for-all" of destruction.
    Mundus vult decipi
    Steve Davis
    That's an excellent summary of the arguments Gerhard. The fact that the researchers felt the need to introduce kin selection where it was not warranted just goes to show the power of ideology, or in this case, where the ideology has become orthodoxy, the power of the urge to conform. There seems to be a widespread disregard within biology for the principles of the scientific method.
    Have you read this one ? Most of everything I agree with Steve that they didn't need to call kin selection into the equation as the whole thing, at least with E. coli, works very nicely with the observed data being enough to explain  cooperation existence in these bacteria
    Steve Davis
    Thanks for the link Catarina, I'll check it out. The unbelievable thing here is that they discovered something wonderful, then spat on it.
    Gerhard Adam
    I guess my problem with kin selection is that it implies a directionality to natural selection that doesn't exist.  Beyond the fact that most organisms simply can't recognize each other at the genetic level, it seems like a contrived explanation for what happens.

    If we consider any form of sexual reproduction then the issue becomes the question of where would parents commit their resources.  It seems clear that they would devote the biggest bulk of their efforts and resources into rearing individuals that become viable adults.

    It doesn't make sense to suggest that resource allocation would be done randomly or in an ad hoc fashion, so in that respect "kin selection" may be viewed as a mechanism.  However, the more successful such a process was, the greater the number of "kin" in future generations would be.  This wouldn't represent a preference for kin because of genetics, but rather "kin" would be a by-product of how parents allocated and used resources.

    I realize this sounds a bit like a "chicken/egg" argument, but we can clearly see that kin becomes less important once a social group forms, since the original benefits of resource allocation are now spread over a larger area.  As a result, the benefit of originally being monogamous are diluted because the group, itself, has become the dominant form of existence.

    My point, is that if kin selection is used as a criteria for determining how natural selection progresses because it favors certain genes over others, then that point fails to be made if kin selection isn't preserved regardless of social groupings.  While it may play a role in initiating certain processes, it doesn't appear robust enough to actually sustain them.  Therefore, I would conclude that "kin selection" may actually be little more than a primitive manifestation of "sociality" and have little or nothing to do with genetic propagation (except as an incidental consequence).
    Mundus vult decipi
    Steve Davis
     it seems like a contrived explanation for what happens.
    I believe that's exactly what it is Gerhard. Contrived for what purpose? To give the appearance that genes play a greater role in evolution than they actually do. To make evolution all about genes, when in fact it's all about organisms and groups.