A research group led by Tetsuhiro Hatakeyama from the Earth-Life Science Institute (ELSI) at Institute of Science Tokyo have revealed how a seemingly self-destructive survival strategy could persist in yeast for hundreds of millions of years. By combining population-dynamics theory with comparative experimental observations, the team found that alternating periods of nutrient-rich conditions and starvation can stabilise this unusual behaviour over evolutionary timescales. The findings were published in the Journal of the Royal Society Interface .
The study addresses a long-standing puzzle in evolutionary biology. Budding yeast and fission yeast diverged approximately 300 to 600 million years ago, yet both retain the same "latecomer-killing" strategy and use the same autotoxins. Why such a costly behaviour has been conserved across such distant species has remained unexplained.
When glucose becomes scarce, yeast cells release toxins into their surroundings. Cells that have already adapted to these toxins survive, while genetically identical cells arriving later, before they have adapted, are killed. This phenomenon, known as latecomer killing, allows cells that have already adapted to a starvation environment to exclude late-arriving, toxin-sensitive competitors, even when those competitors are genetically identical clones.
At first glance, however, the strategy appears evolutionarily unstable. Both toxin production and resistance carry costs. Evolutionary theory predicts that "cheaters," cells that retain resistance but avoid the cost of producing toxins, should eventually outcompete toxin-producing cells. If so, the system should disappear over time.
To investigate this paradox, the researchers developed a population-dynamics model that simulated yeast populations under different environmental conditions.
The results revealed that neither constant nutrient-rich conditions nor continuous starvation could maintain the toxin-adaptation system. Instead, evolutionary stability emerged only when the environment alternated between long nutrient-rich periods and shorter episodes of starvation.
During nutrient-rich periods, cells with the toxin-adaptation system behave much like toxin-sensitive cells, while cheaters still pay the cost of maintaining resistance and are gradually removed from the population. When starvation returns, toxin-adaptation cells switch to producing toxins and resisting them, enabling them to eliminate toxin-sensitive cells. In this way, long nutrient-rich periods suppress cheaters, while shorter starvation episodes suppress sensitive cells, together preserving the strategy over long evolutionary timescales.
"The surprising result was that neither constant abundance nor constant starvation could maintain this system," said Hatakeyama. "Only when the environment switched between the two did the toxin-adaptation strategy become evolutionarily stable. This shows that long-term environmental fluctuations can shape the survival of biological strategies that would otherwise disappear."
The findings suggest that environmental fluctuations can play a much greater role in evolution than previously recognised. Rather than simply selecting the fittest strategy under a single condition, changing environments can preserve complex ecological strategies that become advantageous only through the alternation of different conditions.
The team also compared yeast species across the phylogenetic tree. Budding yeast and fission yeast, which diverged approximately 300 to 600 million years ago, both show latecomer killing and use the same autotoxins. In contrast, two yeast species more closely related to budding yeast did not show clear evidence of latecomer killing. This suggests that whether a species retains or loses the system may reflect its long-term ecological history rather than phylogenetic relatedness alone.
The theory predicts that similar toxin-adaptation systems should be found preferentially in microorganisms that inhabit environments which are generally nutrient-rich but occasionally experience starvation. Testing this prediction through environmental surveys and laboratory evolution experiments could reveal whether comparable strategies occur in bacteria and archaea.
More broadly, the work raises the possibility that these systems preserve clues about a species' long-term ecological history. Understanding how cooperation, competition and adaptation evolve under changing environmental conditions may also provide insights into major evolutionary transitions, including the emergence of multicellular life.
Reference
Tetsuhiro S. Hatakeyama 1* , Kunihiko Kaneko 2 , Kunihiro Ohta 3,4 and Arisa H. Oda 3,4 , Evolvability of the toxin-adaptation system in yeast, Journal of the Royal Society Interface , DOI: 10.1098/rsif.2026.0345
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Earth-Life Science Institute (ELSI) is one of Japan’s ambitious World Premiere International research centers, whose aim is to achieve progress in broadly inter-disciplinary scientific areas by inspiring the world’s greatest minds to come to Japan and collaborate on the most challenging scientific problems. ELSI’s primary aim is to address the origin and co-evolution of the Earth and life.
Institute of Science Tokyo (Science Tokyo) was established on October 1, 2024, following the merger between Tokyo Medical and Dental University (TMDU) and Tokyo Institute of Technology (Tokyo Tech), with the mission of “Advancing science and human wellbeing to create value for and with society.”
World Premier International Research Center Initiative (WPI) was launched in 2007 by Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT) to foster globally visible research centers boasting the highest standards and outstanding research environments. Numbering more than a dozen and operating at institutions throughout the country, these centers are given a high degree of autonomy, allowing them to engage in innovative modes of management and research. The program is administered by the Japan Society for the Promotion of Science (JSPS).
Journal of The Royal Society Interface
Computational simulation/modeling
Cells
Evolvability of the toxin-adaptation system in yeast
22-Jul-2026