THE big surprise from the human genome project was that humans have 20,000 to 25,000 genes 鈥� only twice as many as fruit flies. But now a study has found a big genetic difference between humans and other animals: humans edit their genetic information far more extensively than other vertebrates. Could this explain our complex brains?
When a gene is read, its sequence is copied to an intermediate molecule called messenger RNA (mRNA), which is read in turn to make a protein. It is well known that during the process of making mRNA the cell snips out sequences that don鈥檛 code for protein. But there is another editing process at work 鈥� an enzyme occasionally changes the letter A (adenosine) to I (inosine).
Early last year several research groups reported this 鈥淩NA editing鈥� is very common in human mRNA, particularly short, repeated strings of genomic 鈥渏unk鈥� known as Alu sequences, which make up about 10 per cent of the human genome.
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To test whether humans are unusual in this respect, Eli Eisenberg and colleagues at Tel Aviv University, Israel, and drug company Compugen in Tel Aviv looked for RNA edits by comparing genes in DNA against the corresponding mRNA in various species. They found a total of almost 13,000 edits in humans spread over more than 1600 genes, an average of about one for every 5000 base pairs.
By contrast, mice had more than an order of magnitude fewer edits, only about one per 66,000 base pairs, the team report in the February issue of Trends in Genetics. Edits were similarly rare in rats, chickens and flies. The team put this difference between humans and other animals down to the presence of Alus, which occur only in primates. They have not yet shown that this RNA editing makes any difference to the organism, but it may influence the way genes are expressed.
鈥淚n comparison to human RNA editing, mice have an order of magnitude fewer, and edits are rare in rats and chickens too鈥�
Earlier studies have shown that RNA editing is most common in brain tissue, where editing defects have been linked to depression, epilepsy and motor neuron disease. 鈥淚t鈥檚 tempting to think that maybe the abundant editing in humans has something to do with the increased complexity of the human brain,鈥� says Eisenberg.
On the other hand, RNA editing could simply be a first-aid measure. RNA strands rich in Alus often stick together to form double-stranded structures, which cells quickly destroy. RNA editing prevents the strands from sticking together, sparing mRNA from this fate.
