No need for statins —

Billion-year-old grease hints at long history of complex cells

Our ancestors once thrived on cholesterols that are now just reaction intermediates.

Image of a complex, multi-ringed molecule.
Enlarge / All steroids past and present share the complex ringed structure but differ in terms of the atoms attached to those rings.

All of the organisms we can see around us—the plants, animals, and fungi—are eukaryotes composed of complex cells. Their cells have many internal structures enclosed in membranes, which keep things like energy production separated from genetic material, and so on. Even the single-celled organisms on this branch of the tree of life often have membrane-covered structures that they move and rearrange for feeding.

Some of that membrane flexibility comes courtesy of steroids. In multicellular eukaryotes, steroids perform various functions; among other things, they’re used as signaling molecules, like estrogen and testosterone. But all eukaryotes insert various steroids into their membranes, increasing their fluidity and altering their curvature. So the evolution of an elaborate steroid metabolism may have been critical to enabling complex life.

Now, researchers have traced the origin of eukaryotic steroids almost a billion years further back in time. The results suggest that many branches of the eukaryotic family tree once made early versions of steroids. But our branch evolved the ability to produce more elaborate ones—which may have helped us outcompete our relatives.

A confused timeline

To some extent, the new work involves testing an idea proposed decades ago by the biochemist Konrad Bloch. Bloch won a Nobel Prize for figuring out the biochemical pathways that allow cells to produce steroids from simpler precursors. In 1994, Bloch suggested that the chemical intermediates on the pathways he identified were, at some point in our evolutionary paths, the end products. Cells would make these less complex steroids, which played critical roles in their survival; over time, however, our branch evolved enzymes that further modified them in ways that were advantageous.

This had the potential to make sense out of a variety of evidence that otherwise didn't fit together very well. We've found microfossils as old as 1.6 billion years that seem to show complex cells with surface processes that are typically limited to eukaryotes. That works well with the DNA evidence, which suggests all current eukaryotes can be traced to a common ancestor that existed at least 1.2 billion years ago, perhaps as early as 1.8 billion years ago.

But we can also look for steroids in old rocks, since the molecules are remarkably stable. But the steroids in current eukaryotes don't show up until about a billion years ago—much later than the eukaryotes themselves. That gap could be neatly explained if the earlier eukaryotes were using Bloch's biochemical intermediates.

It was here that Bloch, despite getting so much right, got a big thing wrong. He suggested that the intermediates would be chemically unstable, and so they wouldn't survive in sediments long enough for us to find them. In this view, there was no point in looking.


An international team of researchers decided it might be worthwhile testing Bloch's assumption about the robustness of these molecules. So, the researchers synthesized a bunch and subjected the molecules to heating and accelerated aging conditions and looked at what happened. While they lost a couple of atoms off the side of the ringed structures, most of the molecule survived. And, more critically, no other steroids are known to produce the same molecules when they degrade, so these aged intermediates can serve as tracers of steroid production.

With that information in hand, the researchers obtained oil and bitumen samples from sediments dated to different points in the Earth's past. And even the oldest sample, at 1.6 billion years old, already had lots of the remains of these steroid intermediates. The researchers isolated dozens of relatives of steroid intermediates but found none of the molecules you would expect if modern steroids were present.

Eukaryotes also seem to have been everywhere. "These protosteroids were detected in deep and relatively shallow water environments, microbial mats and pelagic habitats, shales and carbonates, as well as marine and likely lacustrine basins," the researchers write.

Again, the first signs of modern steroids don't appear until less than a billion years ago, suggesting that eukaryotes—both our ancestors and other branches of the evolutionary tree—thrived for nearly a billion years using molecules that are now just chemical intermediates. Different classes of modern steroids also appear slowly in the geological record, suggesting there wasn't a burst of innovation.

Surviving extremes

The researchers propose an intriguing idea that places the origin of modern eukaryotes within the geological record. Eukaryotes seem to have arisen within a geological time period named the "boring billion," which ran from roughly 1.8 to 0.8 billion years ago. During this time, as its name implies, not a lot happened. For most of this time, geology saw Earth's continental plates assembled into a supercontinent, which helped support a seemingly stable climate. Life seems to have responded to the relative stasis by forming equally stable ecosystems that persisted for much of this time.

While the ancestor of all modern eukaryotes probably evolved during the boring billion, the lack of ecological upsets may have meant that it faced a difficult time finding an unoccupied ecological niche. Given that challenge, the researchers suggest, the evolution of modern steroids could potentially have given them the tolerances needed to occupy more extreme environments, such as where cold or high temperatures prevailed or places like mud flats that periodically dried out. This could mean that modern steroids were being made, but only at levels that make their detection unlikely.

The boring billion ended with a rise in tectonic activity and global glaciations, which could have set off the microbial equivalent of mass extinctions. In the turbulent environment that ensued, the ability to tolerate environmental extremes allowed by modern steroids could have given our ancestors an edge, allowing them to push all the other branches of the eukaryotic tree to extinction.

Nature, 2023. DOI: 10.1038/s41586-023-06170-w  (About DOIs).

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