The secret role histones played in complex cellular evolution


that’s why Tobias Warnecke, who studies Archean histones at Imperial College London, believes that “something special must have happened at the dawn of eukaryotes, where we go from simple histones… to octameric nucleosomes. And they seem to be doing something qualitatively different.

What it is, however, remains a mystery. In the Archaean species, there are “quite a few that have histones, and there are other species that do not have histones.” And even those with histones vary a lot, ”Warnecke said. Last December, he published an article showing that there are various variants of histone proteins with different functions. Histone-DNA complexes vary in their stability and affinity for DNA. But they are not organized as stably or evenly as eukaryotic nucleosomes.

As puzzling as the diversity of Archean histones is, it offers an opportunity to understand the different possible ways of constructing gene expression systems. This is something we cannot get out of the relative “boredom” of eukaryotes, says Warnecke: By understanding the combinatorics of archaeal systems, “we can also understand what is special in eukaryotic systems.” The variety of different types and configurations of histones in archaea can also help us infer what they might have done before their role in gene regulation solidified.

A protective role for histones

Because archaea are relatively simple prokaryotes with small genomes, “I don’t think the original role of histones was to control gene expression, or at least not in a way that we are used to by eukaryotes. Said Warnecke. Instead, he speculates that the histones could have protected the genome from damage.

Archaea often live in extreme environments, such as hot springs and volcanic vents on the seabed, characterized by high temperatures, high pressures, high salinity, high acidity, or other threats. Stabilizing their DNA with histones can make it more difficult to merge DNA strands under these extreme conditions. Histones could also protect archaea against invaders, such as phages or transposable elements, which would have a harder time integrating into the genome when it is wrapped around proteins.

Kurdistani agrees. “If you were studying archaea 2 billion years ago, genome compaction and gene regulation are not the first things you would think of when you think of histones,” he said. . In fact, he tentatively speculated about another kind of chemical protection that histones might have offered to archaea.

Last july, The Kurdistani team reported that in yeast nucleosomes, there is a catalytic site at the interface of two H3 histone proteins that can bind and electrochemically reduce copper. To understand its evolutionary significance, Kurdistani traces back to the massive increase in oxygen on Earth, the great oxidation event, which occurred around the time when eukaryotes first evolved over of 2 billion years. Higher oxygen levels must have caused an overall oxidation of metals like copper and iron, which are essential for biochemistry (although toxic in excess). Once oxidized, the metals would have become less available to cells, so any cells that kept the metals in reduced form would have had an advantage.

During the great oxidation event, the ability to reduce copper would have been “an extremely valuable commodity,” Kurdistani said. It could have been particularly attractive to the precursor bacteria of mitochondria, because cytochrome c oxidase, the last enzyme in the chain of reactions that mitochondria use for energy, needs copper to function.

Because archaea live in extreme environments, they may have found ways to generate and manage reduced copper without being killed by it long before the great oxidation event. If so, proto-mitochondria could have invaded Archaian hosts to steal their reduced copper, suggests Kurdistani.

Siavash Kurdistani, a biochemist at the University of California, Los Angeles, speculated how the catalytic abilities of certain histones might have supported the endosymbiosis that produced eukaryotes.Photograph: Reed Hutchinson / UCLA Broad Stem Cell Research Center

The hypothesis is intriguing because it could explain why eukaryotes appeared when oxygen levels rose in the atmosphere. “There were 1.5 billion years of life before this, and no sign of eukaryotes,” Kurdistani said. “So the idea that oxygen led to the formation of the first eukaryotic cell, for me, should be at the center of any hypothesis trying to find out why these characteristics developed.”

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