Infancy of sterol biosynthesis hints at extinct eukaryotic species

In the view of GEITP, this discovery might be very important. Recall that: Prokaryotes (e.g., bacteria) are single cells having a cell wall made of carbohydrates and polysaccharides, no subcellular organelles, and their single-stranded DNA —> mRNA —> protein machinery are all together inside. On the other hand, Eukaryotes (e.g., plants, fungi, animals) are single cells or complex organisms having many cells with cell membranes comprised of steroids and lipids, with double-stranded DNA enclosed in a nucleus with mRNA —> protein machinery in the cytosol that has many distinct subcellular organelles — including mitochondria [which contain mitochondrial DNA (mtDNA) plus their energy-producing respiratory chain complex].

In the history of our planet, eukaryotic life appears to have flourished surprisingly late. This belief is based on the low diversity of diagnostic eukaryotic fossils in marine sediments of the mid-Proterozoic age [~1,600 to 800 million years ago (MYA)], combined with the absence of steranes (the molecular fossils of eukaryotic membrane sterols).

This scarcity of eukaryotics has been difficult to reconcile with molecular clocks suggesting that the last eukaryotic common ancestor (LECA) had already emerged between >1,800 MYA and ~1,200 MYA. LECA, in turn, must have been preceded by stem-group eukaryotic forms by several hundred million years.

Authors [see attached preprint] report the discovery of abundant protosteroids in sedimentary rocks of the mid-Proterozoic age; these primordial compounds had previously remained unnoticed — because their structures represent early intermediates of the modern sterol biosynthetic pathway — as had been predicted by Nobel Laureate Konrad Bloch. The protosteroids reveal an ecologically prominent ‘protosterol biota’ that was widespread and abundant in aquatic environments — from at least 1,640 MYA to ~800 MYA and that probably comprised ancient protosterol-producing bacteria and deep-branching stem-group eukaryotes.

Modern eukaryotes started to appear during the Tonian period (1,000 MYA to 720 MYA), fueled by the proliferation of red algae (rhodophytes) by ~800 MYA. This ‘Tonian transformation’ emerged as one of the most profound ecological turning-points in Earth’s history.

Sterol biosynthesis includes monooxygenase activities, including the presumed earliest cytochrome P450 in eukaryotes, CYP51A1. Cytochrome P450 14α-sterol demethylases (CYP51 family) catalyze the oxidative removal of the 14α-methyl group of lanosterol and 24-methylene-24,25-dihydrolanosterol in yeast and fungi, obtusifoliol in plants, and 24,25-dihydrolanosterol in mammals to give Δ14,15-desaturated intermediates in ergosterol (fungi), phytosterol (plants), and cholesterol (animals) biosynthesis. During the catalytic cycle, a substrate undergoes three successive monooxygenation reactions resulting in formation of 14-hydroxymethyl, 14-carboxaldehyde, and 14-formyl derivatives — followed by elimination of formic acid with introduction of a 14,15-double bond.

For those with an interest in chemical structures, squalene epoxidase is a mixed-function oxidase that is not a cytochrome P450; squalene is a naturally-occurring unsaturated hydrocarbon that precedes (evolutionarily) any oxygen-containing sterol or other steroid chemical [see Fig. 1 of the attached editorial News’N’Views preprint for additional chemical structures in these pathways].

What follows is a lay description of the Nature articles. 😊😊


07 June 2023
A ‘lost world’ of early microbes thrived one billion years ago

Fat-like compounds in ancient rocks point to a vast array of previously unknown microorganisms that once dominated complex life on Earth.

Heidi Ledford

Coloured transmission electron micrograph of a liver cell.

The oceans teemed with eukaryotic micro-organisms (modern eukaryotic cell pictured; artificially colored) more than 1 billion years ago.

Rocks, hundreds of meters beneath the Australian Outback, have yielded clues to a lost world of primitive microbes that once populated the world’s oceans and might have eventually given rise to modern plants and animals.

Analysis of fat-like molecules isolated from the rocks suggests that they were made by a previously undiscovered, ancient population of organisms called eukaryotes, the group of living things whose cells typically contain a nucleus and various intracellular components. The molecules are 1.6 billion years old and hint that eukaryotes were abundant and widespread much longer ago than earlier biochemical evidence had suggested.

“The previous story was that eukaryotes were extremely rare until 800 million years ago,” says Phoebe Cohen, a palaeobiologist at Williams College in Williamstown, Massachusetts, who was not involved in the research. “Palaeontologists really bristled at that, because that’s not what we were seeing in the fossil record.” The findings, she says, help to bridge the gap between the two types of evidence.

The new results were published on 7 June in Nature1.

Chemical fingerprint

Most modern eukaryotes rely on fat-like compounds called sterols, such as cholesterol, to build cell membranes and carry out other cellular functions. Because sterols are found throughout the eukaryotic family tree, they are thought to have been present in the last common ancestor of all modern eukaryotes. For that reason, palaeontologists have used the compounds as a biomarker for the presence of eukaryotes in ancient rocks.

But look further back in time than 800 million years ago, and the sterol-trail runs dry. Researchers have not been able to find traces of the compounds in rocks older than that, despite the existence of fossils of a red and a green alga — both eukaryotes — dating back to about one billion years.

This absence has led to speculation that before 800 million years ago, eukaryotes were not abundant enough to leave a detectable sterol trace.

Another possibility, however, was that researchers were looking for the wrong molecules. Benjamin Nettersheim, a geobiologist at the University of Bremen in Germany, Jochen Brocks, a palaeobiogeochemist at the Australian National University in Canberra, and their colleagues decided to focus on short-lived molecules that modern eukaryotes make while synthesizing sterols. Such modern intermediates might have been the end product for primeval eukaryotes.
Wild ocean

The team combed rocks from around the world and found widespread traces of these ‘protosterols’ — evidence that the eukaryotes that produced them were abundant in water environments between 800 million and 1.6 billion years ago.

This contradicts previous thinking, says Nettersheim. One possibility is that eukaryotes — that made more-modern sterols — gained a selective advantage between one billion and 800 million years ago, eventually displacing their protosterol-making counterparts.

The work could show why scientists could not find biochemical traces to confirm the fossil record, says Laura Katz, a biologist who studies microbial eukaryotes at Smith College in Northampton, Massachusetts. “We were just looking for the wrong thing.”

The mysterious microbes that gave rise to complex living organisms

But Andrew Roger, who studies comparative genomics and the evolution of eukaryotes at Dalhousie University in Halifax, Canada, notes that fossilized red and green algae dating back one billion years look remarkably similar to living algae, and probably made modern sterols. That would suggest that modern sterols — not just their precursors — should also be present in rocks that are more than 800 million years old. “The finding raises as many questions as it answers,” he says.

And although there are reasons to suspect that the protosterols were made by eukaryotes, the researchers have not yet been able to rule out the possibility that they were made by ancient bacteria, says Susannah Porter, a palaeontologist who focuses on early eukaryote evolution at the University of California, Santa Barbara.

But the team’s approach — using hypotheses about the evolution of biosynthetic pathways to guide the search for ancient life — could reveal more about early life, she adds. “It’s thinking about the record of biomarkers from an evolutionary perspective,” Porter says. “And I think that’s needed.”


Read the related News & Views: ‘The long infancy of sterol biosynthesis’

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