Abstract
BackgroundFormal description of a cell's genetic information should provide the number of DNA molecules in that cell and their complete nucleotide sequences. We pose the formal problem: can the genome sequence forming the genotype of a given living cell be known with absolute certainty so that the cell's behaviour (phenotype) can be correlated to that genetic information? To answer this question, we propose a series of thought experiments.ResultsWe show that the genome sequence of any actual living cell cannot physically be known with absolute certainty, independently of the method used. There is an associated uncertainty, in terms of base pairs, equal to or greater than μs (where μ is the mutation rate of the cell type and s is the cell's genome size).ConclusionThis finding establishes an "uncertainty principle" in genetics for the first time, and its analogy with the Heisenberg uncertainty principle in physics is discussed. The genetic information that makes living cells work is thus better represented by a probabilistic model rather than as a completely defined object.
Highlights
Formal description of a cell's genetic information should provide the number of DNA molecules in that cell and their complete nucleotide sequences
The formal problem of knowing the genome sequence in a living cell We pose the formal problem: can the genome sequence forming the genotype of a given living cell be known with absolute certainty so that the cell's behaviour can be correlated to that genetic information? Firstly, the genome being the cell's DNA content [1], we define the description of the total genetic information "I" as a matrix comprising the linear base sequences for the distinct genomic DNA molecules in that cell (Fig. 1)
We propose three thought experiments to show how "I" could be determined with absolute certainty in a living cell, assuming that, after determination of the genome sequence, the original cell is further available for tracing its behaviour, simulating or verifying predictions about its genotype/phenotype relationships, or obtaining derivative cells or organisms
Summary
We show that the genome sequence of any actual living cell cannot physically be known with absolute certainty, independently of the method used. There is an associated uncertainty, in terms of base pairs, equal to or greater than μs (where μ is the mutation rate of the cell type and s is the cell's genome size)
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