Cell division is like an intricate dance, where chromosomes have to follow a tight choreography. The chromosomes first have to find and pair with their partners, proceed with an exchange of DNA and then part ways again. But like the best dancers, chromosomes sometimes make mistakes. If two paired chromosomes are not lined up properly when they start exchanging DNA, one chromosome can take up a larger chunk of DNA than it gives away. If this chunk happens to contain a gene, the chromosome now has an extra copy.

Chromosomes line up during the metaphase.

Most new genes are born through such accidental duplications. Duplicated genes have been described as the raw material that keeps the engine of evolution running. The basic idea behind this metaphor is that one gene acts as a safety net, while its sibling is free to mutate. Such a mutation could break the gene (without serious consequences - its intact twin is still there), or change its function. If the newly evolved function is useful enough, both copies are retained in the genome.

But duplicated genes are not without their downsides. Two identical genes also produce twice as much protein, and this can cause all sorts of troubles for the cell. Freefloating proteins could stick together and form toxic clumps, or bind other proteins which they shouldn't bind for example.

To prevent such a protein overdose, the cell restores balance again by reducing the activity (expression) of both copies. Andrew Ying-Fei Chang and Ben-Yang Liao from Taiwan published a paper this week in which they describe how this works.

They found that the duplicated genes of mice and humans carry methyl groups (a simple chemical modification) than unduplicated ones. These methyl groups don't affect the information that is encoded in the DNA: they are like little signposts that are added on top. Methylated DNA has a reputation for being less active than normal DNA. The methyl groups get in the way of the proteins that normally read the DNA. They also let the DNA coil in a more compact and rigid way, making it less accessible.

Chang and Liao were surprised to find that the cell rebalances duplicated genes with transient methyl groups: "[Such] changes [..] are not as permanent as modifications at the genetic level", they write. Methyl group can be removed fairly easily.

The same researchers previously noted that the reduced activity of duplicated genes is self-perpetuating. Now that gene expression has returned to a normal level, the cell can no longer afford to lose either copy. The spare tires have made themselves essential again. Using methylated DNA to keep duplicated genes in check therefore seems to be a very temporary solution to a long-term problem.

The scenario sketched by the researchers does explain why the genomes from different species, from yeast to man, still contain genetic siblings that both carry out the same jobs in the cell. These are not young genes: some of them have been duplicated million of years ago. This appears to be the other face of duplicated genes. Instead of driving evolution, they can also introduce needless complexity and dependence, in an already crowded genome.


Metaphase by Roy van Heesbeen.


Ying-Fei Chang A, & Liao BY (2011). DNA methylation rebalances gene dosage after mammalian gene duplications. Molecular biology and evolution PMID: 21821837