“Let us try to teach generosity and altruism, because we are born selfish” – Richard Dawkins
The principle of natural selection makes a logical argument in favor of selfishness – given limited resources and an evolutionary mandate to survive and reproduce, an organism should be motivated to act in its own self-interest, even if that comes at the expense of others. Yet the biological world is replete with examples of one organism helping another, sometimes even of a different species, at a cost to itself. Darwin himself recognized the contradiction between his theory and his observations of such behavior: “he who was ready to sacrifice his life...rather than betray his comrades, would often leave no offspring to inherit his noble nature”. How, then, do we explain the evolution of generous behaviors? The answer may be that, at times, the best way to help yourself is to help someone else.
Most organisms live not in isolation, but in communities. Under these conditions, cooperative behaviors can arise. This phenomenon has been seen in many microbial communities, frequently in the form of nutrient sharing. For instance, species A provides a nutrient that species B needs but cannot produce, and species B provides a nutrient that species A needs but cannot produce. But how do cooperative relationships evolve? And what conditions promote the rise of cooperative mutations? A recent paper from the lab of Dr. Wenying Shou in the Basic Sciences Division, led by former technician Samuel Hart (now a UW MCB graduate student) and published in eLife, examined the evolution of cooperative mutations in an experimental community.
It is well known that cooperation – defined by Dr. Shou as “paying a fitness cost to generate benefits available to others” – will evolve under conditions that favor such a relationship. To understand this process, the authors modeled an evolutionary trajectory in a cooperative environment using a simple 2-strain yeast community, called CoSMO (Cooperation that is Synthetic and Mutually Obligatory). One strain, denoted L-H+, lacks the tools to make the essential metabolite lysine, but produces and releases an excess of hypoxanthine, also an essential compound. The second strain, H-L+, cannot produce hypoxanthine, but produces and releases an excess of lysine, resulting in a co-dependent relationship in which each strain relied on the other to survive.

One mechanism that can promote cooperation is the appearance of pleiotropic win-win mutations. Pleiotropy means that a gene can control multiple traits. An example in human is the phenylketonuria (PKU) disorder where defects in an amino acid conversion gene leads to mental retardation, pigment defects, and eczema. The Hart et al. study examined a pleiotropic win-win mutation that directly promotes the fitness of self (“self-serving”) and the fitness of partner (“partner-serving”). Within the evolving CoSMO community, the authors observed that loss-of-function mutations in the ECM21 gene, which they posited may be win-win mutations, arose multiple times in the L-H+ strain. These mutations did appear to be self-serving, as ECM21 mutant yeast grew faster than wild-type yeast under the lysine-limited conditions present in CoSMO, likely by increasing the cells’ affinity for lysine. These mutations also appeared to be partner-serving, as ECM21 mutant yeast produced more hypoxanthine and led to faster growth of the partner H-L+ strain than wild-type yeast.
In evolving to be cooperative, the proper motivations are thought to be critical. Because mutations that promote cooperation are often costly to one’s own fitness, they would be expected to be detrimental, and thus likely would not arise, in conditions that do not favor cooperation. To model such an environment, the authors grew the L-H+ strain alone in media containing low levels of lysine. Surprisingly, they found that the win-win ECM21 mutations frequently arose under this condition as well, suggesting that they could be valuable even absent the need for cooperation. This is due to the self-serving aspect of the mutation. This finding represents somewhat of a paradigm change. Contrary to expectations, “win-win mutations can rapidly evolve even under conditions unfavorable for cooperation.” This finding also has implications for the propensity of organisms to rapidly evolve cooperative behaviors. As the authors point out, if the cooperative mutation can arise prior to the need for cooperation, “[this] suggests the possibility of pre-existing pleiotropy stabilizing nascent cooperation in natural communities.” Interestingly, pleiotropic mutations that link an individual’s ability to grow to the individual’s ability to help others have been found in social amoebae and in bacterial populations.
This work was supported by the National Institutes of Health and the W.M. Keck Foundation.
Fred Hutch/UW Cancer Consortium member Wenying Shou contributed to this work
Hart SFM, Chen C, Shou W. (2021) Pleiotropic mutations can rapidly evolve to directly benefit self and cooperative partner despite unfavorable conditions. eLife 10:e57838 https://doi.org/10.7554/eLife.57838