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Evolution of DNA methylation in animals, plants, and fungi

This week, I will try to explain what DNA methylation is and some of the reasons why it's important, before discussing this week's paper on how DNA methylation has evolved.

The paper is "Genome-Wide Evolutionary Analysis of Eukaryotic DNA Methylation", published in Science by Assaf Zemach and others from the lab of Daniel Zilberman.

DNA methylation usually refers to the attachment of a methyl (CH3) group to a cytosine, one of four DNA bases (C, in DNA's A,T,C,G alphabet). Here's a link showing one way cytidine can get methylated. And this Wikipedia article shows cytosine in place in double-stranded RNA. (DNA would be similar, but with T instead of U.)

The functions of DNA methylation mostly come from the reduced transcription of RNA from methylated stretches of DNA. Surprisingly, when a new DNA copy is made (e.g., when one of our cells divide), methylation patterns are generally copied, too. Together, these two facts explain many of DNA methylation's functions.

First, DNA methylation is key to imprinting, whereby genes inherited from one parent are often shut down, perhaps for life, by methylation. Imprinting often reflects an unconscious battle between male and female parents over whether to maximize growth of this particular offspring, whatever the consequences for the mother's future survival and reproduction, or take or more long-term view. Earlier, I discussed the possible role of imprinting in mental illness.

Second, DNA methylation is important in phenotypic plasticity, whereby individuals with the same genotype may develop different phenotypes in different environments. For example, DNA in embryos developing in mothers on low-protein diets gets methylated differently, with life-long consequences for regulation of blood glucose. In effect, individuals born to poorly nourished mothers develop phenotypes appropriate for starvation conditions.

This role for DNA methylation was presumably inherited from mouse-like ancestors with shorter lives than ours, so that the mother's nutritional environment was likely to be fairly similar to that experienced by her offspring. But humans typically reproduce twenty years or more later than their mother did, perhaps in a very different nutritional environment. If food is much more available later in life than it was for our mothers during pregnancy, we may have methylation patterns that make us more prone to become obese or develop diabetes.

Third, DNA methylation is widely used to shut down transposable elements (TEs), sections of unusually selfish "junk DNA" -- not all nonprotein-coding DNA is junk -- which, left unchecked, would make even more copies of themselves, throughout the genome, than they have already.

But how has DNA methylation changed over the course of evolution? That is the topic of this week's paper. The authors measured DNA methylation throughout the genomes of 17 species, including plants, fungi, and animals, as well as the effects of this methylation on transcription of affected regions into RNA.

There were some remarkable differences among species. Consider CG methylation. This refers to methylation of C when it's next to G, as opposed to just paired with G in the opposite DNA strand, which would be true for almost all C. (Sometimes this type of methylation is referred to as CpG, with the p indicating the phosphate connecting the two bases along the DNA strand.) Selagninella, an "early-diverging" plant, had very low levels of CG methylation throughout the protein-coding region of most genes. Rice, in contrast, had low CG methylation in the promoter region of most genes, but high CG methylation through most of the protein-coding section.

What about the common ancestor of these plants? In other words, was methylation of protein-coding regions gained at some point along the rice branch, or lost at some point along the Selagninella branch? Plants are descended from algae, so they looked at two algae as well. They show data for Chlorella, whose CG methylation is even more enthusiastic than rice, with significant (but less) methylation even in the promoter regions. They also found lots of methylation of transposable elements (TEs, transposons) in the algae and concluded that "methylation of both gene bodies and TEs thus appears to be an ancient property of plants."

More generally, they concluded that:

"Our data indicate that gene body methylation is basal, predating the divergence of plants and animals around 1.6 billion years ago (fig. S1), whereas the antitransposon function probably evolved independently in the vertebrate and plant lineages."

I expect we will be hearing much more about the evolution of DNA methylation and its implications.


Interesting post; thanks.

Long ago, I wondered about the function of restriction enzymes, which respond to DNA methylation too. And I concluded that they might be an anti outbreeding device, ensuring that during bacterial conjugation, and DNA from a strain with a different methylation pattern would be destroyed. I haven't kept up with the field, but I wonder what you think of that.

The main function of restriction enzymes in nature is thought to be cutting up viral (phage) DNA. Bacteria use methylation to protect their own DNA sequences that would otherwise be attacked by their restriction enzymes. Seems like it should be possible to just block conjugation (except when so stressed that it's worth taking a chance on unknown genes), rather than chopping up foreign DNA.

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