Before the evolution of animals, humans and plants, one of the most important evolutionary events on Earth was the development of the nucleus in single-celled organisms. This nucleus is what defines eukaryotes, one of the three main branches of living organisms, and is the structure that protects the genetic material that defines who we are. Now, a team of researchers has uncovered more information on how the nuclear pore complex - the channel-like structure that transports the many molecules that need to pass in or out of our nucleus - came to be.
Prior to the current study, research revealed the nuclear pore complex as a composition of an inner ring in between two outer rings, with one facing in and one facing out. The outer rings possess classes of proteins that are compatible with either the chemistry of the nucleus or cytoplasm, and this asymmetric distribution is what is believed to help push transported materials in and out of the nucleus using the nuclear pore complex.
The nuclear pore complex is a fundamental structure, and its asymmetrical composition was believed to be universal to all eukaryotes. However, a new study reveals a new kind of pore structure in eukaryotes that has never before been studied, implying that the evolution of this structure may be more complex than previously believed.
"We were driven by curiosity about the evolution of the nuclear pore complex," said Samson Obado, first author on the study, pointing to the fact that everything we know about the complex was observed in yeasts and humans. "But what did the original pores look like, and how have they developed in different eukaryotes?"
Obado and his team examined trypanosomes (Trypanosoma brucei), parasites that are responsible for diseases such as sleeping sickness and Chagas disease. This family diverged from those that developed into yeasts, humans and plants around one and a half billion years ago, which just about coincides with the last common ancestor of all eukaryotes.
"Compared with many other eukaryotes, trypanosomes have an unusual and quirky molecular biology," Obado said. "A key example is how they transcribe their genes into messenger RNAs for translation into proteins, which is very different from textbook models. Furthermore, because they are so divergent, you can't just search for gene sequences similar to those in yeast or humans."
The team examined the nuclear pore complex in trypanosomes by walking each protein through it until they had a complete survey of each protein involved in the process. Using electron microscopy, they then determined the location of each component with respect to one another and created the first complete picture of the trypanosome nuclear pore structure.
The results showed that the inner rings of the trypanosome nuclear pore complex are similar to those in yeast, plants and vertebrates, pointing to an ancient origin for the common adaptation.
Conversely, the outer rings show differences that suggest they were not "conserved" as evolution proceeded, the complex possesses a unique mechanism not seen in other organisms that attaches it to the surrounding nuclear envelope, and its overall structure exhibits a near-complete symmetry of its components.
The findings shed light on the origins of the nuclear pore complex and suggest that it evolved before the last ancestor of all eukaryotes.
"These differences may offer something we can target therapeutically without risking harm to our own transport mechanisms," Obado said.
The findings were published in the Feb. 18 issue of PLOS Biology.
