Telomere-based neo-Darwinian selection of yeast clonal subpopulations

Abstract

In Saccharomyces cerevisiae, imbalance of the genes coding for the heterochromatin components Sir3p and histone H4 (namely, overdosage of SIR3 and lack of one of the two genes coding for H4) causes modifications in telomere length and telomere sequence organization, favoring the insertion of Y′ elements into a stably shortened (C_1–3A)_n repeat tract. We report here that the newly inserted Y′ elements are unstable and are lost with high frequency, generating clonal subpopulations with short telomeres, as revealed by the analysis of a specific telomere (LIII) and of the overall population of telomeres. Moreover, the growth rates of the subpopulations with and without Y′ elements on LIII are different, the Y′-less individuals reproducing 20% more slowly than individuals bearing Y′ elements. When grown together with Y′-bearing individuals, the subpopulations with the normal LIII telomere (which are viable and genetically stable if grown alone) are rapidly competed out. Hence, genetic imbalance for the structural components of heterochromatin results in a complex and rapidly changing mixture of subpopulations in such cultures. Thus, in situations where subpopulations are allowed to compete, heterochromatin-based differential growth rates result in neo-Darwinian clonal selection.