For billions of years, the only living organisms on Earth were tiny, primitive bacteria-like cells. Then, 1.5 billion years ago, something amazing happened: A primitive cell belonging to the archaea swallowed a bacterium.
Instead of being digested the bacterium took up permanent residence in the other organism, becoming what biologists refer to as an endosymbiont. It eventually absorbed fully into its archaeal host cells, becoming what we now call the mitochondrion. This is the vital energy-producing component of the cell.
Its acquisition has been long regarded as the crucial step in what has been called the greatest evolutionary leap since the birth of life: the transition from primitive cells (or prokaryotes) to more advanced cells of higher organisms (eukaryotes), which includes us.
This is a fascinating story that you’ll find in biology textbooks. But, is it really that simple? New evidence has disproved the idea that mitochondria played a pivotal role in this transition over the past few years. Researchers have discovered many genes that are not derived from the host or the endosymbiont by sequencing the genomes modern-day relatives of the earliest eukaryotes. Scientists believe that this could indicate that evolution of the first eukaryotes took place with more than two partners, and occurred more slowly than previously thought.
Other scientists don’t think there is a reason to abandon the theory of rapid evolution of eukaryotes. This spark gave rise to animals, plants, and vertebrates eons ago. The debate may be resolved by new evidence from genomics, cell biology, and other sources. However, it also points out knowledge gaps that remain to help us understand one of our ancestors’ most important events, the origins of complex cells.
A Genetic Enigma
Uncertainties were created when mystery genes were discovered in the last decade by researchers Toni Gabaldon and his colleagues at the Barcelona Supercomputing Centre. They used today’s inexpensive gene sequencing technology to examine the genomes of many eukaryotes including some obscure, primitive, and modern-day relatives of early Eukaryotes.
They expected to find genes whose lineage could be traced back to either an archaeal host, or the mitochondrial ancestral, a member a group called alphaproteobacteria. The scientists were surprised to discover that genes from other bacteria were also found. Gabaldon and his colleagues speculated that the cell ancestor of eukaryotes acquired the genes from a variety partners. These partners could have been additional endosymbionts later lost or free-living bacteria who passed a few genes to the ancestral host through a process known as horizontal gene transfer. They suggested that the tango that led eukaryotes was more than two dancers.
“It is clear now that there are additional contributions from additional partners,” says Gabaldon, who wrote about the early evolution of eukaryotes in the 2021 Annual Review of Microbiology.
It’s difficult to pinpoint the origin of these ancient foreign genes because so much time has passed. But there are many more recent, looser endosymbioses where the origin of foreign genes is easier to identify, says John McCutcheon, an evolutionary cell biologist at Arizona State University in Tempe who wrote about endosymbiont evolution in the 2021 Annual Review of Cell and Developmental Biology. These might be used to help us understand how mitochondria and the first Eukaryotes evolved, he suggests.
A prime example is a roughly 100-million-year-old partnership between insects called mealybugs and two bacterial endosymbionts, one nested inside the other in the mealybugs’ cells. (The mealybug cannot get essential amino acids from its diet because the endosymbionts produce them. McCutcheon’s genomic analysis revealed that mealybugs’ metabolic pathways were a mosaic of genes that originated with them, came in with their endosymbionts, or were acquired by horizontal transfer from other microbes. McCutcheon’s group demonstrated that mealybug cells needed to develop an apparatus to transport proteins between previously independent organisms. This allowed proteins from the mealybug nucleus to travel across two sets endosymbiont membranes to be used by the innermost .
Something similar occurs in a single-celled, amoeba-like eukaryote called Paulinella. Paulinella has an endosymbiont, engulfed tens of millions of years ago, that allows it to harvest energy from sunlight without the chloroplast organelles that usually power photosynthesis. Eva Nowack, who is the head of a laboratory at the University of Dusseldorf, Germany, discovered that Paulinella’s genome now includes genes from the endosymbiont, as well as other genes that were acquired by horizontal gene transfer.
Remarkably, the endosymbiont imports more than 400 proteins from the host nucleus, so it also must have evolved a complicated protein transport system like the mealybugs. Andrew Roger, a molecular evolutionaryist at Dalhousie University in Halifax Canada, says that this is quite exciting. It suggests that it is not as difficult to create new transport systems.
These examples show how endosymbionts integrate with their hosts. They also suggest that horizontal gene transfer from different sources may have been common early in the evolution eukaryotes. McCutcheon says, “It doesn’t prove that is what happened in formation of the mitochondria. But it shows that it’s possible.”
Others agree. “There is strong evidence that horizontal gene transfer occurred in eukaryotes during the period of prokaryote to eukaryote transition. There is no reason to believe that it wouldn’t have. Roger believes it almost certainly happened.
Shopping for genes
This suggests that the ancient host could have acquired eukaryotic characteristics one at a moment, much like a shopper picking items up in a shopping bag. This could have been done via horizontal gene transfer or by consuming a series endosymbionts. John Archibald is a comparative genomicist at Dalhousie University. Some of these newly acquired genes may have been useful to the host in the evolution of modern eukaryotic cell machinery.
If so, the ancient host would have already engulfed the precursor to mitochondria by the time it was engulfed by membranes. This would mean that mitochondria would not have been the primary driver of eukaryotic development but a late addition.
Despite all the evidence supporting a gradualist hypothesis regarding the evolution of eukaryotes there are still some questions. First, these more recent endosymbioses might not provide much information about the evolution of eukaryotes. After all, these modern host cells were already eukaryotes in these cases. These examples show how easy it can be, once you have an eukaryotic cells, to establish intracellular symbioses,” states Bill Martin, an evolutionary biologist at the University of Dusseldorf who studies the origins of the eukaryotes. Eukaryotes have all the intracellular machinery necessary to engulf another cells. Martin claims that it is not clear that the proto-eukaryote that was the first to have this ability did not have it. This would increase the barriers to the first endosymbiosis. This, Martin says, is against gradual evolution of the eukaryotic cells.
Some evidence suggests that key features of eukaryotic life were acquired quickly, rather than slowly. Every eukaryote has the exact same set organelles that are familiar to anyone who has studied cell biological sciences: nucleus and nucleolus; rough and smooth endoplasmic retinalum; Golgi apparatus; cytoskeleton; lysosome, centriole and cytoskeleton. (Plants and some other photosynthetic Eukaryotes have an additional organelle, the chloroplast. Everyone agrees that it arose in a separate endosymbiosis. This strongly suggests that the other cellular components originated at roughly the same time. If they didn’t, then different eukaryotic lineages should have different combinations of organelles. Jennifer Lippincott-Schwartz is a cell biologist at Howard Hughes Medical Institute’s Janelia Research Campus, Virginia.
Some biochemical evidence also supports this conclusion. The ancestral host and the endosymbiont were from different branches of tree of life — bacteria and archaea — which use different molecules to build membranes. The membranes of eukaryotic organelles do not have an archaeal structure and it is unlikely that they were derived from the ancestral host cell. This suggests that the archaeal host cell was simple and evolved its other organelles after the arrival of a mitochondrial ancestor.
But, what about all the mysterious foreign genes that were recently discovered in the eukaryotic tree? Martin suggests another explanation. Martin suggests that all those foreign genes could have been in one package, with the endosymbiont which evolved into the mitochondrion. Because bacteria can swap genes easily, those genes could have spread to many bacterial groups in the 1.5 billion years that followed. This would lead to the false impression that multiple people contributed genes to the early Eukaryote.
Martin also stated that, if the gradualist theory is true, different lineages should have fundamentally and measurably distinct collections of genes. However, he has proven they don’t. Martin states that there is no evidence to suggest serial acquisitions. “A single acquisition at the origin of eukaryotes of mitochondria is sufficient .”
The debate is unlikely to settle soon. Roger says that it is difficult to find data that will allow us to distinguish between these alternative options. However, Roger says that further research on primitive, obscure eukaryotes could reveal some that only have a subset eukaryotic organelles. This could support the gradualist hypothesis. If evidence were found that an archaeal cell could acquire a endosymbiont, it would make the “mitochondria young” hypothesis more plausible.
“People love big questions. The more difficult they are, the more people will be drawn to them and engage in debates about them,” Archibald says. That’s what makes it fun .”
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