Epigenetics and Evolution

We share most of our genome with our closest relatives, the other great apes, and yet each species looks and acts quite different from the others. How is this possible? If humans, chimps, and bonobos share around 99% of our DNA, how come we're so different?

An explanation that has emerged over the last several years is that the differences between great apes don't come solely from differences in what genes we have, but also in how they're regulated. Extremely similar genomes can still give rise to different organisms if the genes are activated at different times and strengths. Genes are generally activated when a specific protein binds to their promoter, a short stretch of DNA just before the start of each gene; the protein then reads the DNA that constitutes the gene and makes an RNA "working copy" which is used by the cell. Cells can regulate the activity of a particular gene by controlling when and how these proteins bind to its promoter.

Cells use an abundance of methods to accomplish this, from managing which proteins have access to the nucleus to changing the structure of proteins to control or destroy them. While those are fascinating and important processes (and the subject of a whole field of study!), they're not the subject of this post. Instead, I'd like to focus on epigenetic modifications, adjustments to the DNA which don't change the sequence itself (the string of A,T,G, and C) but still affect how it gets read. Epigenetic modifications are a bit like ornaments on a Christmas tree; the tree (the DNA sequence) is still the same, but the decorations (epigenetic modifications) change how it's perceived.

Two major kinds of epigenetic modifications are methylation, where a chemical group (a methyl) is attached to the DNA in specific locations, and histone modification, chemical modifications of a histone, a scaffolding protein in the nucleus which acts as a spool around which DNA is wound. Methylation usually reduces the activity of a gene, either by blocking proteins from binding to its promoter or by recruiting other proteins that wrap the DNA up and make it inactive. Histone modifications can affect how accessible a region of DNA is, making a gene more or less active. One way to understand how these modifications can alter gene expression without changing the DNA sequence is to think of the effect font has on text. Precisely the same letters arranged into the same series of words can have a different impact if the font emphasizes certain words:

My mistress' eyes are nothing like the sun;
My mistress' eyes are nothing like the sun;
My mistress' eyes are nothing like the sun;

Over the past few years, several studies have compared the epigenetic modifications of our genome with that of other great apes, leading to an emerging picture of the importance of epigenetics in our recent evolutionary history. Last year, Shulha et al compared the prevalence of a specific histone modification in DNA from human, chimpanzee, and macaque neurons; they found nearly 500 genes with a human-specific modification pattern. Draft versions of the gorilla and bonobo genome published last year enabled researchers to expand their analysis to include a wider range of great apes. Hernando-Herraez et al did just that in a paper published this month. By comparing the methylation patterns in the genomes of all great ape species, they discovered that each one had a distinct pattern, including 171 genes specifically methylated in humans, 101 in Pan species (chimps and bonobos), 101 in Gorilla species, and nearly 450 in Pongo species.

The role of epigenetics in evolution (particularly primate evolution) is an active and exciting area of research; these are just two examples that I've picked from a wide range of papers on the topic. If you're interested in learning more, have a look at the (open access!) papers below and the references they cite. In evolution, as in everything else, it's not what you've got; it's what you do with it.

Further reading
Shulha HP, Crisci JL, Reshetov D, Tushir JS, Cheung I, et al. (2012) Human-Specific Histone Methylation Signatures at Transcription Start Sites in Prefrontal Neurons. PLoS Biology 10(11): e1001427. doi:10.1371/journal.pbio.1001427

Hernando-Herraez I, Prado-Martinez J, Garg P, Fernandez-Callejo M, Heyn H, et al. (2013) Dynamics of DNA Methylation in Recent Human and Great Ape Evolution. PLoS Genetics 9(9): e1003763. doi:10.1371/journal.pgen.1003763

Image credit
Chimpanzee image by psyberartist on Flickr; uploaded by russavia to Wikimedia Commons
Christmas tree image by Malene Thyssen via Wikimedia Commons