Geneticists Are Finally Hunting For The Mysterious Genes That Still Lurk In Our DNA

A database meant to shrink, not grow.

DNA structure on black background design element
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In the 1995 sci-fi dystopian Gattaca, genetic engineering is as easy as changing a lightbulb. As such, no one’s DNA is left untouched. But in our real world, gene editing tools like CRISPR make futures of designer babies and genetic discrimination feel painfully conceivable (actually, it’s already happened). Even more frightening, many proteins encoded in the human genome remain largely unknown, and, as a result, we don’t really understand what their genes do.

But this might change soon. Scientists in the U.K. have created an open database they hope will encourage others in the scientific community to uncover the function of these mysterious genes. Dubbed the “unknome,” each protein is ranked along a “knownness” score based on how much or little scientists know about them. The researchers hope this database will dwindle in size in the coming years, providing new biological and potential therapeutic insights.

The researchers described the database in a paper published Tuesday in the journal PLOS Biology.

Since scientists published the first draft of the human genome in 2000, they’ve known that there were pieces of the human genome left that hadn’t been categorized. This mysterious DNA didn’t appear to code for anything worthwhile, and researchers at the time even deemed it “junk DNA.” But over the past few decades, this “junk DNA” has proved itself to be vital to human functioning. In 2022, geneticists finally decoded the remaining eight percent of the human genome.

Despite this shift in understanding, the paper’s researchers say DNA whose purpose we still don’t fully understand still lurks in our genome, and understanding it could prove key to unlocking some of the mysteries of the human body and how it works.

The researchers selected 260 human genes that had corresponding genes in flies. These genes had very low knownness scores (meaning we know very little about their functioning) in both species. Then, with the help of the gene-editing tool CRISPR, the researchers selectively deleted these genes from the fly genome. They found that the genes appeared to affect a range of functions such as fertility, development, tissue growth, and resilience to stress.

“These uncharacterized genes have not deserved their neglect,” Sean Munro, head researcher of cell biology at the MRC Laboratory of Molecular Biology in Cambridge, said in a press release. “Our database provides a powerful, versatile, and efficient platform to identify and select important genes of unknown function for analysis, thereby accelerating the closure of the gap in biological knowledge that the unknome represents… [and demonstrating] how ignorance can drive biological discovery.”

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