After the origin of life, the only living things on Earth were tiny, primitive cells. One of those primitive cells, belonging to a group known as the archaea, swallowed another, different one.

The bacterium took up permanent residence in the other organisms instead of being eaten. The crucial energy-production component of the cell was integrated fully into its archaeal host cell.

The most important evolutionary leap since the origin of life is the transition from early primitive cells to the more sophisticated cells of higher organisms.

It is a neat story, but is it really that simple? In the last few years, new evidence has challenged the idea that mitochondria played a major part in this transition. Many genes that don't seem to come from either the host or the endosymbiont have been found by researchers. Some scientists think that the evolution of the first eukaryotes may have been more gradual than thought.

Some people don't see a reason to abandon the idea that the acquisition of the Mitochondrion sparked the rapid evolution of the organisms. Fresh evidence from cell biology may help resolve the debate, as well as pointing to knowledge gaps that still need to be filled to understand the origin of complex cells.

A Genetic Enigma

Uncertainties arose when mystery genes turned up in the last decade, when researchers including Toni Gabaldn, an evolutionarygenomicist at the Barcelona Supercomputing Centre, and his colleagues took advantage of today's cheap gene sequencing technology to explore the genomes of a wide range of eukaryote

They were expecting to find genes that came from either the archaeal host or the alphaproteobacteria. The genes that were found were from a wide range of otherbacteria. According to Gabaldn and colleagues, the cellular ancestors of eukaryotes had acquired genes from a number of partners. The partners could have been other free-livingbacteria that passed some of their genes to the ancestral host. They suggested that the tango that led to eukaryotes involved more than one dancer.

Gabaldn said that there are additional contributions from additional partners.

It's difficult to know where those ancient foreign genes came from. There are many more recent, looser endosymbioses where the origin of foreign genes is easier to identify. He says that studying these might give us a chance to understand how the first genes could have evolved.

A 100 million-year-old partnership between insects called mealybugs and two bacterium is a prime example. The mealybug can't get essential Amino Acids from its diet. The mealybugs have a mosaic of genes that come from the bugs themselves, as well as from other microbes in the environment, according to a new analysis. In order to make this work, mealybug cells had to evolve an apparatus that transports proteins to and fro between what were once independent organisms.

There is something similar in a single-celled amoeba. A long time ago, a body of water engulfed tens of millions of years ago allowed it to harvest energy from the sun. The genes that were acquired through horizontal gene transfer have been discovered by Eva Nowack.

You can sign up for Scientific American's newsletters.

The mealybugs must have evolved a complicated transport system due to the fact that the endosymbiont imports more than 400 proteins. It suggests that evolving these transport systems anew isn't as hard as previously thought.

The examples show how genes can be transferred from one source to another and suggest that horizontal gene transfers could have been common early on in the evolution of the Eukaryotes. It doesn't show what happened in the formation of the mitochondria, but it shows that it's possible

others agree There is a lot of evidence for horizontal gene transfer in eukaryotes, so there is no reason to think that it couldn't have happened during that time. Roger says it almost definitely did happen.

Shopping for genes

The implication is that the ancient host could have gradually acquired traits one at a time, like a shopper picking up items in a bag. The host could have been helped by some of the newly acquired genes.

If so, by the time the ancient host engulfed the precursor of mitochondria, it would have already possessed many eukaryotic features, including some organelles, the internal compartments surrounded by membranes and a late addition to the family.

There are some reasons for doubt despite all the evidence. The first is that the more recent endosymbioses don't tell us a lot about what happened in the past. Bill Martin is an evolutionary biologist who studies the origins of eukaryotes at the University of Dusseldorf. Eukaryotes have all the equipment needed to destroy another cell. It is not clear if the ancestral Proto-eukaryote had that ability. The argument against a gradual evolution of the cell was made to him.

Trichomonas vaginalisGiardia lamblia and Trypanosoma brucei (left to right) are all considered primitive eukaryotes. Biologists sequencing the genomes of these and other unusual eukaryotes have found some unexpected genes that do not appear to have come from either the original eukaryotic host cell or its mitochondrial symbiont. That may mean that other partner species also contributed to the origin of eukaryotes. Credit: CDC/ Joe Miller (left); CDC/ Dr. Stan Erlandsen (middle); Gull Lab, Sir William Dunn School of Pathology (CC BY 4.0) (right)

Evidence shows that key features were acquired all at once. The nucleus, ribosomes, Golgi apparatus, lysosome and centriole are all part of the same set of cells. Everyone agrees that the chloroplast is an extra in plants and a few other Eukaryotes. According to a cell biologist at the Howard Hughes Medical Institute, the other cellular components all started at the same time.

There are some biochemical evidence that supports that. Different branches of the tree of life use different types of molecule to build their membranes. It is unlikely that the archaeal in structure of the erythrocytes came from the original host cell. This suggests that the archaeal host was a simple cell that only evolved its other parts after the arrival of the Mitochondrial Ancestor.

What about the foreign genes found in the family tree? Martin says there is another possibility. The foreign genes could have come in a single package. Thanks to the ease with whichbacteria swap genes to and fro, those genes could have ended up in many different groups. It would be a mistake to think that multiple partners contributed genes.

If the gradualist idea is correct, there should be fundamentally different collections of genes, but he has shown they don't. There is no evidence that there was a lot of acquisitions. A single acquisition of mitochondria is all that's needed.

The debate isn't likely to be resolved soon. Roger says it is difficult to find data that will make us distinguish between the alternatives. The gradualist hypothesis could be strengthened if further studies of obscure, primitive eukaryotes revealed some that only have a subset of the erythropoietin. The "mitochondria early" hypothesis would be more plausible if evidence was found for a way that a simple archaeal cell could acquire an asymbiont.

The harder a question is to answer, the more people are drawn to it. It is fun because of that.

The article was first published in Knowable Magazine. You must sign up for the newsletter.