New genes arise from non-coding DNA
For most of the last 40 years, scientists thought that new genes simply arose from copies of existing genes. The old version went on doing its job, and the new copy became free to evolve novel functions.
Certain genes, however, have no known relatives, and they bear no resemblance to any other gene. The mystery of where these orphan genes came from has puzzled scientists for decades. But in the past few years, a once-heretical explanation has quickly gained momentum — that many of these orphans arose out of so-called junk DNA, or non-coding DNA.
Some scientists say they may even be common. Just last month, research presented at the Society for Molecular Biology and Evolution in Vienna identified 600 potentially new human genes.
Researchers are beginning to understand that de novo genes seem to make up a significant part of the genome, yet scientists have little idea of how many there are or what they do. What’s more, mutations in these genes can trigger catastrophic failures.
The Orphan Chase
The standard gene duplication model explains many of the thousands of known gene families, but it has limitations. The first evidence that a strict duplication model might not suffice came in the 1990s, when DNA sequencing technologies took hold. Researchers analyzing the yeast genome found that a third of the organism’s genes had no similarity to known genes in other organisms.
Yet creating a gene from a random DNA sequence appears as likely as dumping a jar of Scrabble tiles onto the floor and expecting the letters to spell out a coherent sentence. The junk DNA must accumulate mutations that allow it to be read by the cell or converted into RNA, as well as regulatory components that signify when and where the gene should be active. The gene must also have short codes that signal its start and end.
In addition, the RNA or protein produced by the gene must be useful. Newly born genes could prove toxic, producing harmful proteins like those that clump together in the brains of Alzheimer’s patients.
A Wave of New Genes
Scientists have now catalogued a number of clear examples of de novo genes: A gene in yeast that determines whether it will reproduce sexually or asexually, a gene in flies and other two-winged insects that became essential for flight, and some genes found only in humans whose function remains tantalizingly unclear.
Unfortunately, deciphering the function of de novo genes is far more difficult than identifying them. Evidence suggests that a portion of de novo genes quickly become essential. About 20 percent of new genes in fruit flies appear to be required for survival. And many others show signs of natural selection, evidence that they are doing something useful for the organism.
In humans, at least one de novo gene is active in the brain, leading some scientists to speculate such genes may have helped drive the brain’s evolution. Others are linked to cancer when mutated, suggesting they have an important function in the cell.
De novo genes are also part of a larger shift, a change in our conception of what proteins look like and how they work. De novo genes are often short, and they produce small proteins. Rather than folding into a precise structure — the conventional notion of how a protein behaves — de novo proteins have a more disordered architecture.
Scientists don’t yet know a lot about how these shorter proteins behave, largely because standard screening technologies tend to ignore them. Most methods for detecting genes and their corresponding proteins pick out long sequences with some similarity to existing genes.
That’s starting to change. As scientists recognize the importance of shorter proteins, they are implementing new gene discovery technologies. As a result, the number of de novo genes might explode.
