Abstract
Genetics and epigenetics are tightly linked heritable information classes. Question arises if epigenetics provides just a set of environment dependent instructions, or whether it is integral part of an inheritance system. We argued that in the latter case the epigenetic code should share the universality quality of the genetic code. We focused on DNA methylation. Since availability of DNA methylation data is biased towards model organisms we developed a method that uses kernel density estimations of CpG observed/expected ratios to infer DNA methylation types in any genome. We show here that our method allows for robust prediction of mosaic and full gene body methylation with a PPV of 1 and 0.87, respectively. We used this prediction to complement experimental data, and applied hierarchical clustering to identify methylation types in ~150 eucaryotic species covering different body plans, reproduction types and living conditions. Our analysis indicates that there are only four gene body methylation types. These types do not follow phylogeny (i.e. phylogenetically distant clades can have identical methylation types) but they are consistent within clades. We conclude that the gene body DNA methylation codes have universality similar to the universality of the genetic code and should consequently be considered as part of the inheritance system.
Highlights
Living organisms are biological systems in which the complex interaction between different elements such as the nuclear genotype and epigenotype factors and the environment brings about a phenotype that develops and evolves over time[1,2]
Evolution is based on the selection of phenotypic variants that must (i) confer a reproductive advantage to the individual, and (ii) are heritable, i.e. information how to generate the phenotypic variants in response to an environment are passed from parents to offspring
Genetic information is expressed under influence of environmental cues to bring about the phenotype, a process known as G × E→ P43
Summary
Living organisms are biological systems in which the complex interaction between different elements such as the nuclear genotype and epigenotype factors and the environment brings about a phenotype that develops and evolves over time[1,2]. Global conclusions about the function and importance of DNA methylation are based on a very limited and biased amount of data For this reason, it remains challenging to derive the general rules (if any) that govern DNA methylation in the different branches of the “tree of life”. A potential solution to the caveat that experimental “wet bench” data is missing is to infer DNA methylation indirectly with computational method[24,25] The basis for this is that methylated CpG sites mutate relatively frequently compared to the other dinucleotides over evolutionary time[26]. We have developed a new tool, called Notos, to identify DNA methylation signatures within CpGo/e ratios based on kernel density estimations[36] This novel algorithm delivers robust descriptions of frequency distributions of CpGo/e ratios for up to 172,000 input sequences
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