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What if there were a way that didn’t involve CRISPR to give your offspring a natural talent for athletics?
Well that’s totally possible as it turns out, because scientists just demonstrated it in mice, and it didn’t even involve so-called “good genes”.
It involved a modern and exciting field of genetic biology called epigenetics: a term that refers to adaptations to genetic expression in response to life stressors. Here, the actual nature of the DNA doesn’t change, but adaptations packaged in the similarly important RNA made their way into sperm cells, the embryo, and the offspring.
The story of this fascinating innovation begins in Nanjing University, where lead investigator on the study Xin Yin used to notice during his time as an undergraduate that the children of athletes seemed to possess a natural talent for sports. The reproductive biologist didn’t really see the sense in it; certainly, genes coding for larger lung volume would increase a child’s ability to run, but what could explain having a ‘knack’ for what takes months and years of training to master? There’s no gene that codes for having a knack.
This curiosity led Yin to launch a research project with a fellow reproductive biologist at Nanjing to see whether a male mouse’s mastery of treadmill running could somehow imprint onto his offspring. Together with his co-authors, Yin subjected male mice to treadmill work everyday for 2 weeks before breeding them with female mice who did not exercise.
What they found was remarkable. The mice thusly born possessed more oxidative muscle fibers, could run for longer on treadmills, and were more resistant to weight gain from a high-fat diet, than the offspring of sedentary male and female mice. During the study period, Yin and his team sequenced the microRNA snippets in the sperm cells and the fertilized egg, and after observing the significant athletic adaptations, went back to see what might be causing it.
Exercise boosts the levels of a protein called PGC-1 alpha in muscle cells, where it activates genes that build more mitochondria, the organelles responsible for cellular energy and metabolism. PGC-1A is suppressed by another protein called NCoR1. In the exercised mice, sperm-bound microRNAs which proliferate under conditions of exercise target, once inside the mouse embryo, NCoR1. In effect, these RNAs released a natural, cellular brake on the development of metabolic power and muscle function.
A true breakthrough
To triple check whether or not classic genetic transfer was behind this adaptation for countering NCoR1, the researchers looked through 10 of the microRNAs that seemed most likely confer the exercise benefits, selected one in particular, and injected it into embryos fertilized by untrained fathers. Just that action alone, a single, non-DNA molecule, was enough to reproduce the endurance benefits seen in trained fathers.
Biologists commenting on the study to Science Magazine said they were “surprised” that a single RNA could have such an impact.
With that in mind, and to investigate whether similar effects were at work in humans, the team collected sperm from 8 men who trained regularly and 24 others who didn’t. An examination revealed that the equivalents of 7 of the 10 miRNAs seen in the mouse model were elevated in the sperm of trained men.
It’s the first study to show that RNA can pass down the benefits of exercise, commented Colin Conine, an epigeneticist at the University of Pennsylvania, who was not involved in the work but who called it “really a novel paradigm”. It probably suggests that the lifestyle choices of fathers need to be looked at with more scrutiny than in the past, he said.
Caveats included that the endurance/exercise benefit was only seen in male offspring, suggesting the sperm microRNAs only make it through the paternal germline. Grandchildren never received the benefit their parents did.
Yin’s study couldn’t go so far as to investigate the mechanism behind the transfer: why and how did exercise affect sperm? How did the microRNAs pass through the blood-testes barrier? How did they reach the epididymis, the tubes where sperm cells mature? They had time and data to present two hypotheses: that exercise codes for the creation of small-extracellular vesicles which themselves have the capacity to bring microRNA through the testes-blood barrier, or that within the blanket hormonal response of exercise, steroids and thyroid hormones may alter microRNA expression in sperm directly, without relying on the blood stream.
The authors are now extremely curious to know what other effects microRNAs packaged in sperm cells are having on the father’s offspring. WaL
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