Institute of Bioinformatics Münster


From bacteria to mammals, the DNA content of genomes has increased by about three orders of magnitude in just 3 billion years of evolution. Early DNA association studies showed that the human genome is full of repeated segments, such as Alu elements, that are represented by hundreds of thousands copies. The vast majority of a mammalian genome does not code for proteins. So, the question is, "Why do we need so much DNA?" Most researchers have assumed that repetitive DNA elements do not have any function: They are simply useless, selfish DNA sequences that proliferate in our genome, making as many copies as possible. The late Sozumu Ohno coined the term "junk DNA" to describe this part of a genome.

Although catchy, the term "junk DNA" for many years repelled mainstream researchers from studying noncoding DNA. Who, except a small number of genomic clochards, would like to dig through genomic garbage? However, in science as in normal life, there are some clochards who, at the risk of being ridiculed, explore unpopular territories. Because of them, the view of junk DNA, especially repetitive elements, began to change in the early 1990s. Now, more and more biologists regard repetitive elements as a genomic treasure. Genomes are dynamic entities - new functional elements appear and old ones become extinct. It appears that transposable elements are not useless DNA. They interact with the surrounding genomic environment and increase the ability of the organism to evolve. They do this by serving as recombination hotspots, and providing a mechanism for genomic shuffling and a source of "ready-to-use" motifs for new transcriptional regulatory elements, polyadenylation signals, and protein-coding sequences. The last of these is especially exciting because it has a direct influence on protein evolution.

More than a decade ago, Mitchell et al. showed that a point mutation in an Alu element residing in the third intron of the ornithine aminotransferase gene activated a cryptic splice site, and consequently led to the introduction of a partial Alu element into an open reading frame. The in-frame stop codon carried by the Alu element resulted in a truncated protein and ornithine aminotransferase deficiency. This discovery led to the hypothesis that a similar mechanism may result in fast evolutionary changes in protein structure and increased protein variability. Several genome-wide investigations have shown that all types of mobile elements in all vertebrate genomes can be used in this way.

Our view of the entire phenomenon of repetitive elements has to now be revised in light of data on their biology and evolution, especially in the light of what we know about the retroposons. The repetitive elements interact with the whole genome and influence its evolution. As such, repetitive elements should be called genomic scrapyard rather than junk DNA.

2009-11-16 10:30