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How humans got a new gene that makes our brains larger

Image of an animated brain with legs and arms, lifting weights.
Enlarge / Building a bigger brain requires new genes, not a workout.

On the DNA level, there’s not much to distinguish humans from our closest relatives: chimpanzees and bonobos. At stretches of DNA that line up, human and chimp sequences are well over 90 percent identical. And, for the most part, the DNA does line up at genes; there are very few genes that are either human- or chimp-specific.

That has meant most of the focus on understanding human evolution has been on small changes that can alter the timing or level of gene activity, and thus have an effect that’s not proportionate to the number of bases changed.

But that’s not to say that newly evolved genes are irrelevant to human evolution. A paper released this week looks into how a class of new genes evolved since our split with our simian relatives. After gaining some insight into how this class evolved, the team behind the work looked at one of these newly evolved genes and found that it plays a key role in building bigger brains.

From RNA to proteins

Most of the genes we talk about encode proteins. The information in DNA is transcribed into a messenger RNA, which is then translated into a protein. If the protein’s not made, then the gene doesn’t do anything. But we’ve known for nearly 70 years that this isn’t the only option. A number of genes that are transcribed into RNA aren’t translated into proteins. Instead, the RNA performs a critical function.

Since the discovery of the first of these functional RNAs in the 1950s, the list of them steadily grew, and there are now many classes of functional, non-protein-coding RNAs. These do everything from altering the activity of protein-coding genes to maintaining the ends of chromosomes to splicing out unused pieces of messenger RNAs.

One of these classes is the long non-coding RNAs, or lncRNAs. These tend to start a lot like messenger RNAs, in that parts of the initial RNA are spliced out, and special caps are placed on both ends to make them harder to break down. But, instead of being sent out to be translated into proteins, lncRNAs stay in the cell’s nucleus with its DNA, where they’re used to control the activity of other genes.

Studies of genes that are new to species, however, showed that the differences between lncRNAs and messenger RNAs sometimes break down over the course of evolution. A number of protein-encoding genes in one species were found to not code for anything in related species and instead function as lncRNAs there. This suggests that mutations have converted some of the genes for lncRNAs into protein-coding genes.

The new work focused on identifying whether this is a factor in human evolution. Using public genome databases, the researchers compared the genomes of humans, chimps, and the more distantly related macaques. They found 29 cases where lncRNAs had evolved into protein-coding genes since the ancestors of humans and chimps had split off from macaques. Another 45 genes underwent this process since humans split off from the ancestors of chimps and bonobos.

With those in hand, the researchers asked what was distinct about these newly formed genes.

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