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An ancient gene stolen from bacteria set the stage for human sight

The eye is so complex that even Charles Darwin was at a loss to explain how it could have arisen. Now, it turns out that the evolution of the vertebrate eye got an unexpected boost—from bacteria, which contributed a key gene involved in the retina’s response to light. The work, reported today in the Proceedings of the National Academy of Sciences, drives home the evolutionary importance of genes borrowed from other species.

“Their findings demonstrate how complex structures like the vertebrate eye can evolve, not only by modifying existing genetic material but also by acquiring and integrating foreign genes,” says Ling Zhu, a retinal biologist at the University of Sydney’s Save Sight Institute who was not involved with the work. “It’s incredible.”

Bacteria are known to readily swap genes, packaged in viruses or mobile pieces of DNA called transposons, or even as free-floating DNA. But vertebrates, too, can incorporate microbial genes. When the human genome was first sequenced in 2001, scientists thought it contained about 200 bacteria-derived genes, though the microbial origins of many did not hold up.

Hoping to improve on those earlier efforts, Matthew Daugherty, a biochemist at the University of California San Diego, and colleagues used sophisticated computer software to trace the evolution of hundreds of human genes by searching for similar sequences in hundreds of other species. Genes that seemed to have appeared first in vertebrates and had no predecessors in earlier animals were good candidates for having jumped across from bacteria, particularly if they had counterparts in modern microbes. Among the dozens of potentially alien genes, one “blew me away,” Daugherty recalls.

The gene, called IRBP (for interphotoreceptor retinoid-binding protein), was already known to be important for seeing. The protein it encodes resides in the space between the retina and the retinal pigment epithelium, a thin layer of cells overlying the retina. In the vertebrate eye, when light hits a light-sensitive photoreceptor in the retina, vitamin A complexes become kinked, setting off an electrical pulse that activates the optic nerve. IRBP then shifts these molecules to the epithelium to be unkinked. Finally, it shuttles the restored molecules back to the photoreceptor. “IRBP,” Zhu explains, “is essential for the vision of all vertebrates.” 

Vertebrate IRBP most closely resembles a class of bacterial genes called pepsidases, whose proteins recycle other proteins. Since IRBP is found in all vertebrates but generally not in their closest invertebrate relatives, Daugherty and his colleagues propose that more than 500 million years ago microbes transferred a pepsidase gene into an ancestor of all living vertebrates. Once the gene was in place, the protein’s recycling function was lost and the gene duplicated itself twice, explaining why IRBP has four copies of the original pepsidase DNA. Even in its microbial forebears, this protein may have had some ability to bind to light-sensing molecules, Daugherty suggests. Other mutations then completed its transformation into a molecule that could escape from cells and serve as a shuttle.

Not everyone agrees that the evolution of IRBP was crucial for vertebrate vision. “I don’t think it had to happen” in order for vertebrates to see well, says Sönke Johnsen, a biologist at Duke University. Invertebrate eyes make do without IRBP, he notes. Instead of shuttling back and forth, the vitamin A complex stays put in the retina, where one wavelength of light bends the light-sensing molecule, while another unbends it. Some researchers have speculated that mechanism hampers invertebrates’ night vision. Yet “there are plenty of extremely good invertebrate eyes,” Johnsen says.

Daugherty agrees that vertebrates’ reliance on IRBP could simply be a historical accident. “We are sort of stuck with it,” Daugherty says.

Either way, the work supports the idea that horizontal gene transfer can help to endow organisms with new functions, says Julie Dunning Hotopp, a genome biologist at the University of Maryland School of Medicine’s Institute for Genome Sciences. Once these genes take root in a new species, evolution can tinker with them to produce totally new abilities or enhance existing ones. “It is the biological equivalent of upcycling that happens in my Buy Nothing Group.”

Source: Science Mag