An evolutionary perspective on the Crabtree effect

Abstract

The capability to ferment sugars into ethanol is a key metabolic trait of yeasts. Crabtree-positive yeasts use fermentation even in the presence of oxygen, where they could, in principle, rely on the respiration pathway. This is surprising because fermentation has a much lower ATP yield than respiration (2 ATP vs. approximately 18 ATP per glucose). While genetic events in the evolution of the Crabtree effect have been identified, the selective advantages provided by this trait remain controversial. In this review we analyse explanations for the emergence of the Crabtree effect from an evolutionary and game-theoretical perspective. We argue that an increased rate of ATP production is likely the most important factor behind the emergence of the Crabtree effect.

Keywords: Crabtree effect; evolution of metabolism; evolutionary game theory; respiro-fermentation; yeast energy metabolism.

Figure 1

Yeast energy metabolism. Yeasts have two pathways for ATP production from glucose, respiration, and fermentation. Both pathways start with glycolysis, which results in the production of two molecules of pyruvate and ATP per glucose. In fermentation, pyruvate is then turned into ethanol. This process does not produce additional ATP but recycles the NAD⁺ consumed in glycolysis and thereby provides a way of oxygen-independent ATP production. In respiration, pyruvate is completely oxidized to CO₂ through the TCA cycle and oxidative phosphorylation (OXPHOS), which yields additional ATP but requires oxygen. Crabtree positive yeasts, at sufficient levels of oxygen and glucose, use fermentation and respiration simultaneously. The ethanol that accumulates in the environment can be recycled for ATP production once glucose has been depleted. This process, however, yields less ATP than the direct oxidation of pyruvate because the synthesis of Acetyl-CoA from ethanol requires ATP.

Figure 2

Rock-Scissors-Paper dynamics of toxin production. In the game Rock-Scissors-Paper, two players simultaneously have the choice between three strategies, “Rock,” “Scissors,” and “Paper.” Each strategy beats and is beaten by one other strategy: “Rock” beats “Scissors,” “Scissors” beats “Paper,” and “Paper” beats “Rock.” In this game there is no ESS as no one strategy can dominate both of the other strategies (Kerr et al., ; Nowak and Sigmund, ; Biernaskie et al., 2013). Rock-Paper-Scissor has been analyzed through models (Károlyi et al., ; Prado and Kerr, ; Biernaskie et al., 2013) and experimentally in plant systems (Lankau and Strauss, ; Cameron et al., 2009), bacterial systems (Kerr et al., ; Nahum et al., 2011) and lizards (Sinervo, 2001). In particular, toxin production in microbial systems has been shown to follow the rules of Rock-Paper-Scissor (Kerr et al., ; Nahum et al., 2011). In this system, toxin production is costly, as is resistance. A toxin-producing strain can out-compete a strain that is susceptible to the toxin. A resistant strain can out-compete the toxin-producing strain because it is resistant, but does not pay the costs of toxin production. In the absence of a toxin producer, the susceptible strain can out-compete the resistant strain because it does not pay the costs for resistance, thereby completing the cycle of mutual invasibility. If ethanol production and resistance to ethanol are costly traits, one might expect Rock-Paper-Scissor dynamics to influence the interactions between Crabtree-positive and Crabtree-negative yeasts.

Figure 3

Efficiency of resource use—a Public Goods Game. In a Public Goods Game (or Tragedy of the Commons, Hardin, 1968), a number of players can invest in a public good. The returns from the investment are shared among all players, irrespective of the investment. Without any additional mechanisms in place, players that refrain from investing will receive a larger net payoff than players that do invest. In the figure, for instance, investments are doubled and then split evenly between all players. 4 players (shown in blue) invest $10, one does not invest (shown in red); everyone receives a return of $16. The net payoff for the investing players ($6 = $16 – $10) is smaller than the payoff for the player that does not invest ($16 = $16 – $0). The well-studied Prisoner's Dilemma (Rapoport, 1965) can be seen as a 2-player version of the Public Goods Game. For micro-organisms, a number of traits have been identified that can potentially create public goods, for example the excretion of exo-enzymes such as invertase (Greig and Travisano, ; West et al., 2006). Trade-offs between rate and efficiency in the use of shared resources have been shown to lead to a Public Goods Game. In the context of RYT this implies that aerobic fermentation can be seen as a selfish trait (Pfeiffer et al., 2001).