Germs, junk and jumping genes: the latest issue of Genome Biology is now online

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After last month's special issue, Genome Biology has spent November in epigenomics detox. Instead we've been answering questions such as: How does your skin microbiome respond to a wound? If all those bits of the genome that spawn non-coding RNAs really aren't junk, then what is their function? And, how do CpG island promoters relate to chromatin states? (I guess that detox was incomplete.)

John Rinn

If there was ever a good candidate for junk DNA, then endogenous retroviruses (or ERVs) must be it. These mobile elements hop about from one bit of the genome to another, seemingly interested only in their own proliferation. All they know is how to copy-and-paste themselves, so how can they be of any use? But Genome Biology Editorial Board Member John Rinn, who was once summed up by PopSci as a "dropout skate rat turned ace biologist", posited that ERVs might actually be important in driving beneficial change in the genome.

Rinn, a lncRNA (long non-coding RNA) specialist, asked whether ERVs might have a role to play in lncRNA evolution, which is known to occur much faster than that of protein-coding RNAs. Together with his post-doc David Kelley (author of Genome Biology's hugely popular QUAKE article), Rinn found that lncRNA sites in the genome were indeed enriched for ERVs and that this was especially true around regulatory regions, suggesting that ERVs may be responsible for turning lncRNA transcripts 'on' or 'off'. As detailed in a feature in The Economist spotlighting this work, a particularly interesting observation was made about an ERV known as HERVH, which is shown to play a big role in transcriptional regulation of lncRNAs, but specifically in stem cells.

The ceRNA hypothesis

This is all very interesting, but have we just shifted the problem one step along? ERVs might be useful in regulating lncRNAs, but what is the point in all these lncRNAs, if they don't code for proteins? Even Chris Mason's wonderfully revised Central Dogma (see our epitranscriptomics Opinion article) cannot really answer this question. While we already know of a variety of diverse functions for individual lncRNAs, there is one theory that hopes to assign a function to whole swathes of them: the controversial and potentially paradigm-shifting ceRNA hypothesis. ceRNAs are RNA transcripts that can cross-regulate the abundance of one another through competition for a finite pool of shared miRNAs, and this behavior is independent of any protein-coding function that an RNA may have. A small number of specific examples have been published, but it is unknown whether ceRNAs are a widespread phenomemon or merely a quirk restricted to a handful of transcripts.

Chris Ponting

Ana Marques, Chris Ponting (also an Editorial Board Member) and colleagues wondered if the ceRNA hypothesis may explain the curious retention of many pseudogenes, which really ought to be junk, in mammalian genomes. They looked for evidence that some of these pseudogenes, which are genes that by definition have lost their protein-coding function, may retain their roles as non-coding ceRNAs, leading them to be preserved by natural selection.

Elsewhere in the issue, Ben Lehner shows how transcription-associated histone modifications differ between genes with and without CpG island promoters; an investigation monitors both the surface and deeper layers of the skin microbiome following superficial injury; and an analysis of pneumococci isolates dating from 2007 all the way back to 1937 tracks the emergence of the PMEN1 multi-drug resistant strain. Drug resistance in microbes is of course the real fast lane of evolution, leaving lncRNAs and ERVs far behind in their wake.