Ancient enzymes adapted to a cooler Earth to keep life’s chemical reactions going

Re-creating 3-billion-year genetic history of adenylate kinase reveals evolutionary path

adenylate kinase enzyme bond

HOT AND COLD Scientists reconstructed three billion years of genetic history for the adenylate kinase enzyme (shown here bound to another molecule) to see how ancient enzymes might have adapted to a cooler Earth.

Ayacop/Wikimedia Commons 

Like lifelong Floridians dropped into a Wisconsin winter, enzymes accustomed to warmth don’t always fare well in colder climes. But ancient heat-loving enzymes forced to adapt to a cooling Earth managed to swap out parts to keep chemical reactions going, scientists report online December 22 in Science.

By reconstructing enzymes as they might have looked billions of years ago, the research “helps to explain the natural evolutionary history of life on this planet,” says Yousif Shamoo, a biochemist at Rice University in Houston who wasn’t part of the study. And the findings question the idea that enzymes must sacrifice their stability to become more active.

Enzymes are natural catalysts that jump-start essential chemical reactions inside living things. Most work only within a specific temperature range. Too cold, and they can’t get going. Too hot, and they lose their shape — and by extension, their function.

Life on Earth is believed to have started out in warm environments like hot springs or hydrothermal vents, so the first enzymes probably worked best in those toasty temperatures, says study coauthor Dorothee Kern, a biochemist at Brandeis University in Waltham, Mass. But gradually, Earth cooled. For life to continue, early enzymes had to shift their optimal temperature range.

Kern and her colleagues looked at the evolutionary history of an enzyme called adenylate kinase. Some version of this protein is found in every cell, and it’s essential for life to survive.

The researchers used a technique called ancestral sequence reconstruction to figure out what the enzyme’s genes might have looked like at different points in the last 3 billion years. The scientists edited E. coli’s genes to make the bacteria produce those probable ancient enzymes, and then looked at how the reincarnated molecules held up under different temperatures.

“These very old enzymes were way more lousy at low temperatures than anyone expected,” says Kern. But over time, natural selection gradually pushed the enzymes to work better at cooler temperatures, she found. The enzymes accumulated mutations that swapped some of their amino acid building blocks, ultimately lowering the enzymes’ energy demands. That let the enzymes keep moving essential reactions along at a fast-enough pace for life to survive. 

There wasn’t a corresponding disadvantage to also working well in heat, so the enzymes didn’t immediately lose their heat tolerance. Some of them became what Kern calls “superenzymes” — they worked impressively fast and could catalyze reactions at low temperatures, but they remained stable at high temperatures.

That finding goes against a widely held assumption that an increase in an enzyme’s activity — which would allow it to keep trucking at the same speed at lower temperatures — typically comes with a corresponding decrease in stability.

That assumption was a logical one: Like chilly fingers struggling to tie shoelaces, enzymes get stiffer and don’t work as well when the temperature drops. To up their activity, they‘d need to increase their flexibility. That could make them less stable at higher temperatures — more likely to lose their shape and stop working. But now, it seems that some enzymes can have the best of both worlds.

The idea of a generalist enzyme that works well across a wide temperature range isn’t new — scientists have engineered such proteins in the lab, Shamoo says. But this work shows it might have happened in a real-world setting. “Just because I can do something in the laboratory, that I can build an enzyme that’s a true generalist, doesn’t mean that’s how it happened on this planet,” he says.

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