Micro-RNA 941

2 minute read

John Timmer covers the story of miR-941, a micro-RNA that may influence the expression of genes in human brains, and which appears to have taken on a novel role in our lineage compared to other primates:

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.

The research was carried out by Hai Yang Hu and colleagues Hu:2012 in an open access paper (“Evolution of the human-specific microRNA miR-941”. It deserves a bit more attention than I can give it at the moment, as it is one of a series of recent papers demonstrating human-specific duplications that affect gene expression. It is one of the first cases in which RNA structure and function have been investigated in an ancient genome. The number of copies of miR-941 varies substantially both within and among human populations.

This passage from the paper is provocative:

Humans display both increased longevity and increased occurrence of certain forms of cancer compared with both chimpanzees and macaques39. It is, therefore, appealing to speculate that emergence of miR-941 enhanced the maintenance of adult stem cell populations, thus supporting longer human lifespan, but rendering human cells more prone to malignant transformation. The role of miR-941 in the regulation of insulin signaling adds support to this notion. The insulin-signaling pathway was consistently implicated in lifespan regulation in many species, including humans. Notably, experimentally verified targets of miR-941 within this pathway include genes directly shown to be involved in lifespan extension in model organisms: IRS1, PPARGC1A and FOXO140 (ref. 40). Furthermore, FOXO1 was linked to extended human longevity.

Still, I am skeptical of the idea that this molecule had a strong effect on the human phenotype. The greater the network of genes influenced by this micro-RNA, the less likely a massive up-regulation or down-regulation will have a simple phenotypic effect. Most genes that were duplicated or deleted during our evolutionary history probably were free to change because of a lack of fitness effect. Maybe this micro-RNA is an exception – with a new effect on the human lineage, and extensive variation in copy number within humans. But it seems more likely to me that the variation in miR-941 dosage leads to a minor phenotypic effect across the network of affected genes, not a major directional effect.