Mutation-rate plasticity and the germline of unicellular organisms

Abstract

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

Germline Evolution: Sequestered Cells or Immortal Strands?

“…Recent papers have proposed that the Immortal Strand Hypothesis could also explain the low mutation rate of fungi [11,17] and other modular organisms including unicellular organisms [18]. If hyphal-tip cells preferentially inherit template-DNA strands during cell division and subapical daughter cells inherit copy-DNA strands, mutations due to copy errors will be inherited by the subapical cells, and thus most often be short lived.…”

Clonal evolution and genome stability in a 2,500-year-old fungal individual

“…The third 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 [26]. In Armillaria, this would mean that cells in the rhizomorph tip would retain the old DNA, whereas the subtending cells (committed to local, deadend development) would receive the new DNA.…”

Asymmetry, division of labour and the evolution of ageing in multicellular organisms

“…between pluripotent stem cells with germ-line-like features and cells or tissues with some soma-like properties) plays a major role in the evolution of ageing [ 26 ], perhaps even for cases of negligible senescence. Remarkably, recent work by Aanen & Debets [ 89 ] and others suggests that the distinction between germ-line and soma might be more profound than previously thought and might extend to unicellular organisms: for instance, based on empirical observations that at high cell density mutation rates are strongly reduced in both prokaryotic and eukaryotic unicellular organisms, and that some ‘mother' cells continue dividing whereas their ‘offspring' cells stop dividing, Aanen and colleagues have found evidence to suggest that the observed reduction in mutation rate at high density can be explained if mother cells preferentially retain the template DNA strands, thereby confining new mutations to non-dividing daughter cells—a phenomenon similar to the separation of germ-line and soma. This so-called ‘Immortal Strand Hypothesis' [ 90 ] is also consistent with data on mutation accumulation from fungi [ 91 – 94 ].…”