Systematic genome sequence differences among leaf cells within individual trees

Abstract

BackgroundEven in the age of next-generation sequencing (NGS), it has been unclear whether or not cells within a single organism have systematically distinctive genomes. Resolving this question, one of the most basic biological problems associated with DNA mutation rates, can assist efforts to elucidate essential mechanisms of cancer.ResultsUsing genome profiling (GP), we detected considerable systematic variation in genome sequences among cells in individual woody plants. The degree of genome sequence difference (genomic distance) varied systematically from the bottom to the top of the plant, such that the greatest divergence was observed between leaf genomes from uppermost branches and the remainder of the tree. This systematic variation was observed within both Yoshino cherry and Japanese beech trees.ConclusionsAs measured by GP, the genomic distance between two cells within an individual organism was non-negligible, and was correlated with physical distance (i.e., branch-to-branch distance). This phenomenon was assumed to be the result of accumulation of mutations from each cell division, implying that the degree of divergence is proportional to the number of generations separating the two cells.

Ordered genome change of plant and animal body cells revealed by the genome profiling method

“…This means that if the mutation rate is constant throughout the g generation proliferation, then the total amount of mutation, μ(g) , is simply represented by Eqn . In contrast, as we could detect differences between neighboring sections and microcubes by the GP method; therefore, the number of mutation must be higher than the GP's detection limit (approximately 1 mutation/10 4 nucleotides) . Therefore, …”

“…Finally, the GP analysis was able to discriminate differences between close genomes (i.e., those generated during short term body growth or differentiation), such as neighboring leaf sections (~mm distance) and microcubes of brain slices (~200 μm distance). The GP method and genome distance have already been used with success in several other studies . This evokes a novel, difficult problem in rationalizing the total amount of mutation, μ(g), introduced in a previous study , where the genome distance between two leaves taken from different branches was dealt with as follows: where μ c and g represent the constant mutation rate (/base/generation) of cells and the number of generations of cells, respectively.…”

“…In the previous paper , 10 5 was applied to g since the cell‐to‐cell distance was sufficiently large (branch‐to‐branch distance: ~2 m). However, if we make an order estimation on this study, g can be ~1000 generations at most, considering the cell size (≧10 μm), the slice‐to‐slice or mc‐to‐mc displacement (~1 mm and ~100 μm, respectively), and ages (32 days for Arabidopsis and 60/90 days for zebrafish) together with the proliferation speed of eukaryotic cells (a small number of division/day).…”

“…Until very recently, there was a basic idea that, except for epigenetic differences, genomic DNA is uniform throughout a body; although, there may be differences from one individual to another. This idea was challenged by studies of certain tree leaves where the genomes of an upper branches were different from those of the lower branches . These findings raised the question of whether each cell in a body has a different genome.…”

“…However, these studies used abnormal cells (cancer cells), and did not examine the cells in a systematic way. Therefore, the basic question of whether normal cells in a body have systematic mutations has remained unanswered until now, with the exception of genomic DNA differences in leaves of upper and lower branches .…”