2022/02/09

More evidence of epigenetic control of non-random DNA alterations

Epigenetic modifications affect the rate and the location of DNA alterations


https://www.nature.com/articles/s41467-021-26108-y

Excerpts: "Deletion mutants lacking epigenetic modifications confirm that histone mark H3K27me3 increases whereas H3K9me3 decreases the mutation rate. Furthermore, cytosine methylation in transposable elements (TE) increases the mutation rate 15-fold resulting in significantly less TE mobilization. Also accessory chromosomes have significantly higher mutation rates. Finally, we find that temperature stress substantially elevates the mutation rate. Taken together, we find that epigenetic modifications and environmental conditions modify the rate and the location of spontaneous mutations in the genome and alter its evolutionary (My comment: adaptive) trajectory."

"Field isolates of Z. tritici also differ in the presence of a functional DIM2, the methyltransferase responsible for cytosine methylation (5-methylcytosine (5mC)), and we could recently show that a functional DIM2 results in a higher rate of C → T transitions restricted to TEs."

"Posttranslational histone modifications shape the chromatin condensation state from euchromatin to heterochromatin. In filamentous fungi trimethylation of lysine 9 of histone H3 (H3K9me3) is associated with constitutive heterochromatin and the suppression of transcription and transposition of transposable elements (TEs). In contrast, the trimethylation of the lysine 27 of histone H3 (H3K27me3) is associated with facultative heterochromatin that is enriched in the subtelomeric regions and in accessory genome compartments, and, in some species, also regulates gene expression."



"We show that in Z. tritici H3K27me3 increases, whereas H3K9me3 decreases the mutation rate, while the accessory chromosomes overall have a significantly higher mutation rate than the core chromosomes. In addition, 5mC DNA methylation increases the mutation rate substantially and results in less TE mobilization. The mutation rate also increases upon mild temperature stress."

"5mC in Zt10 is associated with a high level of C → T transitions—specifically at CpA sites in TEs. In IPO323 and Zt05, no such high levels of transitions are present. The increased level of C → T transitions in TEs caused by the presence of the dim2 gene is likely a mechanism to inactivate TEs."

"Our study shows, with experimental data so far unprecedented for any other species, that different epigenetic modifications directly affect the mutation rate."

"In conclusion, this study determines the mutation rate and mutational spectrum in a pathogenic fungus, and demonstrates the importance of epigenetic modifications in shaping the mutation rate variation. The results underline that Z. tritici, with its complement of histone modifications and DNA methylation that are mostly absent from the experimental model species S. cerevisiae and S. pombe, provides an attractive eukaryote system to establish the underlying mechanisms of mutations and genome evolution."

Summary and conclusions:
  • Cytosine methylation in certain genomic areas increases the mutation rate 15-fold.
  • So called accessory chromosomes are almost entirely heterochromatic indicating that they contain a lot of faulty DNA material.
  • Posttranslational histone modifications shape the chromatin condensation state from euchromatin to heterochromatin. --> The cell uses epigenetic mechanisms by which it is able to suppress DNA and prevent it from being transcribed.
  • DNA is controlled by epigenetic mechanisms and factors.
  • Adaptive DNA changes are not directionless, random alterations but accurate  modifications driven by epigenetic mechanisms.
  • The theory of evolution has lost its basic tenets.