Asymmetrical template-DNA strand segregation can explain density-associated mutation-rate plasticity

Abstract

6The mutation rate is a fundamental factor in evolutionary genetics. Recently, mutation 7 rates were found to be strongly reduced at high density in a wide range of unicellular 8 organisms, prokaryotic and eukaryotic. Independently, cell division was found to 9 become more asymmetrical at increasing density in diverse organisms; in yeast, some 1 0 'mother' cells continue dividing, while their 'offspring' cells do not divide further. Here, 1 1 we investigate how this increased asymmetry in cell division at high density can be 1 2 reconciled with reduced mutation-rate estimates. We calculated the expected number of 1 3 mutant cells due to replication errors under various modes of segregation of template-1 4 DNA strands and copy-DNA strands, both under exponential and under linear growth. 1 5 We show that the observed reduction in the mutation rate at high density can be 1 6 explained if mother cells preferentially retain the template-DNA strands, since new 1 7 mutations are then confined to non-dividing daughter cells thus reducing the spread of 1 8 mutant cells. Any other inheritance mode results in an increase in the number of mutant 1 9 cells at higher density. The proposed hypothesis that patterns of DNA-strand 2 0 segregation are density dependent fundamentally challenges our current understanding 2 1 of mutation-rate estimates and extends the distinction between germline and soma to 2 2 unicellular organisms. 2 3 2 4soma distinction, immortal strand hypothesis, mutation rate, unicellular organisms 2 5

Clonal evolution and genome stability in a 2500-year-old fungal individual

“…The fourth possibility is that the distribution of DNA strands after replication is asymmetric. Cells perpetuating the lineage might tend to receive old DNA while cells committed solely to local development and not to perpetuating the lineage would receive new DNA [28]. In Armillaria, this would mean that cells in the rhizomorph tip would retain the old DNA, whereas the subtending cells (committed to local, dead-end development) would receive the new DNA.…”

Scheduling and Control of Parts in FMS industry

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