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GEN News Highlights : Jan 24, 2014

Selective Pressures at Work When Genes Arise from Noncoding DNA

Scientists on the track of de novo genes—the few genes not present among ancestral genes—have found them in rice, yeast, rodents, humans, and (of course) fruit flies. Moreover, at least some of these de novo genes appear to originate from ancestrally nongenic sequences. This finding, which suggests that new genes needn’t arise from modifications of existing genes, still leaves scientists wanting to know more. Exactly how, they ask, do genes arising from noncoding DNA originate and spread?

A partial answer comes from researchers at the University of California, Davis (UC-Davis). They decided to widen the scope of de novo gene evolution studies by taking a population-based perspective. The results of their work appeared January 23 in Science Express, in an article entitled “Origin and Spread of de Novo Genes in Drosophila melanogaster Populations.”

According to the article’s authors, evidence for de novo genes has generally derived from a combination of phylogenetic and genomic/transcriptomic analyses. Typically these analyses reveal evidence of lineage- or species-specific transcripts associated with nongenic orthologous sequences in sister species. However, because these studies of de novo gene evolution use comparative rather than population genetic approaches, they are limited in their ability to characterize the earliest steps in de novo gene origination.

To overcome the limitations of the comparative approach, the UC-Davis researchers decided to use population genomic and transcriptomic data from D. melanogaster and its close relatives to investigate the origin and spread of de novo genes within populations. Like other de novo gene studies in Drosophila, the UC-Davis study focused on tissues associated with male reproduction. The ease with which de novo genes are found in Drosophila testis, the UC-Davis researchers realized, is an indication that sexual or gametic selection may be important.

The researchers looked at RNA transcripts, which correspond with expressed genes, in the testes of several wild-derived strains of the fruit fly D. melanogaster, and compared them to transcripts expressed in the standard reference sequence strain and in two closely related species. They found 248 new genes that exist only in D. melanogaster, just over a hundred of which were “fixed,” or already spread throughout the population.

These genes, it appeared, emerged from ancestrally noncoding DNA since D. melanogaster split from its close relative, D. simulans. The new genes also showed evidence of being under selection, meaning that they were spreading through the population as flies carrying them gained an edge in reproduction.

The de novo genes fell into two broad classes: genes found at high frequency and those found a low frequency. The high-frequency genes tended to be larger and more complex, suggesting that they had more significant functions.

"This is the first example of totally new genes still spreading through a species," said Li Zhao, a postdoctoral researcher at UC-Davis and first author on the paper. The study, added David Begun, professor of evolution and ecology at UC Davis and senior author on the paper, “shows very clearly that genes are being born from ancestral sequences all the time.”

The authors speculate that new genes can form when a random mutation in the regulatory machinery causes a piece of noncoding DNA to be transcribed to RNA. Then, if the newly coding material has a beneficial effect, it gets selected.

The importance of this mechanism in generating de novo genes is still unclear. Specifically, it is not known whether an alternative mechanism—the duplication and divergence of existing genes—is more important in the creating new genetic material.