The completion of human and primate genome sequences (including some close, extinct relatives) reveals a great deal about the evolutionary innovations behind modern humans. All indications are a large collection of relatively subtle genetic changes added up to considerable differences in our brains and anatomy.
So, it was a bit shocking to see a headline claiming a single gene separated us from our fellow apes. The article behind the headline turned out to be wrong, of course. But there was an additional research paper behind that article. The story this told turned out to be rather interesting, even after the hype was stripped away.
The second paper was the product of a research group studying the evolution of human micro RNAs. These are short pieces of RNA that form a "hairpin" structure: two stretches of complementary sequence that can base pair to form a double helix, separated by a short loop that lets the RNA fold back on itself.
Micro RNAs, unlike messenger RNAs, don't code for other proteins. Instead, they help control which messenger RNAs do get made into proteins. The hairpin structure is recognized by a complex of proteins inside the cell, which process it in a way that leaves a short guide sequence exposed. The guide sequence can then base pair with sequences on messenger RNAs, leading the protein complex to them. The complex will typically either block the messenger RNA from being translated into protein or cause it to be destroyed altogether.
The net result of this: a single micro RNA can determine whether a much larger number of genes are made into proteins. In that sense, they act a lot like the proteins that bind to DNA and regulate the activity of large collections of genes.
To find micro RNAs that might be involved in human evolution, the authors of the new study identified over 1,400 micro RNAs known to be active in human cells. Next they searched for the equivalent sequences in the genomes of 10 other mammalian species (as well as, for some reason, the chicken). Most of these seem to have appeared in our ancestors' genomes long before humans were a species, but 10 of them appeared to be unique to us. And another dozen have mutations in key regions that help determine their activity.
Since the authors were interested in human-specific activity, they looked in an organ that's got distinctive features in humans: the brain. Most of the collection wasn't active there, but one was—miR-941.
Looking at the region in the human genome that contains miR-941 showed it's an area with a series of repeats of the same sequence, arranged in tandem. Chimps and macaques have similar sequences, but the duplications aren't arranged in a way that allows the production of a hairpin structure. Somewhere after we split off from chimps 6 million years ago, a rearrangement in the area (an event that's common in areas with duplicated sequences) created the human form of miR-941. It was already in place a million years ago, when the Denisovan population branched off.
But the rearrangements didn't end there, as there have been a series of duplications that created as many as 11 extra copies of miR-941 (the numbers vary in different populations, but average is about six or seven copies in most). The extra copies should help ensure it's expressed at higher levels than it would be otherwise.
A variety of evidence indicated it's likely to be having a significant impact on gene regulation. miR-941 is expressed in a variety of tissues, and the sequences it recognizes are present in two important signaling pathways that contribute to the growth and structures of the brain (hedgehog and insulin) and other tissues. And, if you express it in the cells from other primates, it is able to shut a variety of genes down. In humans, several of those genes no longer respond to miR-941 due to mutations in their sequence. This suggests the appearance of the micro RNA caused a period of fine-tuning of its targets (in order to more precisely control its regulation of gene expression).
So, the authors propose a model where, somewhere after our ancestors had branched off from chimps, a DNA rearrangement produced miR-941. That probably had a mix of effects, some beneficial, some harmful. But further mutations quickly allowed us to escape from the impacts of the harmful ones, leaving us with a valuable new regulatory circuit to control gene expression.
Is this the one change that made us human? Clearly not, since we already know about a variety of other, seemingly significant genetic differences between us and chimps. But it's certainly plausible that miR-941 contributed to the changes that make humans distinctive. Unfortunately, the authors are going to have a hard time testing that. The stretch of DNA that encodes miR-941 is right in the middle of another gene that helps control neural function, and the only known genetic defect in the area takes out both of them. But the defect does produce changes in brain and behavior.
Nature Communications, 2012. DOI: 10.1038/ncomms2146 (About DOIs).
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