Costs, benefits and redundant mechanisms of adaption to chronic low-dose stress in yeast.

All organisms live in changeable, stressful environments. It has been reported that exposure to low-dose stresses or poisons can improve fitness. However, examining the effects of chronic low-dose chemical exposure is challenging. To address this issue we used temperature sensitive mutations affecting the yeast cell division cycle to induce low-dose stress for 40 generation times, or more. We examined cdc13-1 mutants, defective in telomere function, and cdc15-2 mutants, defective in mitotic kinase activity. We found that each stress induced similar adaptive responses. Stress-exposed cells became resistant to higher levels of stress but less fit, in comparison with unstressed cells, in conditions of low stress. The costs and benefits of adaptation to chronic stress were reversible. In the cdc13-1 context we tested the effects of Rad9, a central player in the response to telomere defects, Exo1, a nuclease that degrades defective telomeres, and Msn2 and Msn4, 2 transcription factors that contribute to the environmental stress response. We also observed, as expected, that Rad9 and Exo1 modulated the response of cells to stress. In addition we observed that adaptation to stress could still occur in these contexts, with associated costs and benefits. We conclude that functionally redundant cellular networks control the adaptive responses to low dose chronic stress. Our data suggests that if organisms adapt to low dose stress it is helpful if stress continues or increases but harmful should stress levels reduce.