Revealing the Origin of Eukaryotes

Tracing the breadcrumbs of deep phylogeny through gene duplications. 

Last week, we discussed the jamboree of mutation that is the MHC locus in animals. One part of that story was the persistent duplication and pseudogene-i-zation (which is to say, the birth and death) of genes in that locus through primate evolution, another consequence of the never-ending arms race with our pathogens. Gene duplication has much deeper significance, however, as it has given rise to new genes throughout biological evolution, as it is merely an accident of DNA (or RNA) replication, thus operationally rather frequent. Significant transitions, such as the advent of eukaryotes, and the advent of plants and of angiosperms, all feature rapid gene duplication, even whole-genome duplication, which provide grist for new functions, refinement of old functions, and speciation.

A recent paper did a deep dive into the origin of eukaryotes, perhaps the watershed event in the history of life, second only to the origin of life itself on the early Earth. It is very difficult to reconstruct what happened during these extremely early events, which these authors put as long as three billion years ago. There has been so much mutational churn in our molecules, and no fossil record to speak of, that, again like the origin of life itself, we do not have a great deal to go on. Thankfully, the discovery of the kingdom of archaea, and its especially eukaryotic-like class, the Asgard archaea, has provided a much better platform for speculating about what the originating organisms might have been like.

Eukaryotes differ from bacteria and archaea by numerous characteristics, implying extensive development/evolution before the last common ancestor from which we can trace all the extant descendants. These include the eponymous nucleus, an internal system of membranes and membrane-bound organelles, a complex cytoskeleton of both actin and microtubules, a mitochondrion, meiosis, a microtubule spindle-driven division system, and many other, more obscure molecular differences. The lack of intermediate forms is certainly frustrating from a scientific perspective, making it difficult to go through the catalog of life today to identify the steps involved in this transition. It also implies that the process ended with an evolutionary bang that in essence caused the final iteration to wipe out all the preceeding forms, a bit like humans vs the many other Australopithecines and their descendents. 

These differences are enormous and momentous, making eukaryotic cells far larger, energetically capable, and complex than their antecedents. Another key characteristic is a prevalence of gene duplication and specialization, leading to much larger genomes along with all the other complexity. It has long been theorized that the union of the proto-mitochondrion, which was a bacterium, with the archaeal founding cell that set the whole process off, particularly providing the massive amount of energy required for all this rise in complexity. However the current authors claim definitively that this is not the case, that the mitochondrial symbiosis was a rather late event, coincident with the oxygenation of the atmosphere about two billion years ago (GYA). The authors argue that, since gene duplication and specialization is in any case a clear characteristic of eukaryotes, using molecular clocks to time these duplications can give us the epochs at which the processes they participate in first developed. 

The authors present estimated times of origin for key duplications involved in RNA synthesis. The RNA polymerases I, II, and III were duplicated from one polymerase in archaea, and are composed of numerous gene products, as well as ancillary regulatory proteins. While some subunits are still shared, the ones that duplicated did so in the range of 2.3 to 2.8 billion years ago, before the symbiosis with the mitochondrial precursor, timed at "mFECA", or the mitochondrial first eukaryotic common ancestor, about 2.2 billion years ago. "nFECA" is nuclear first eukaryotic common ancestor, while "LECA" is last eukaryotic common ancestor.

For example, eukaryotes all have three RNA polymerases, while bacteria and archaea only have one. These RNA polymerases specialize on mRNA synthesis (RNA pol II), ribosomal RNA synthesis (RNA pol I), and tRNA, 5S RNA and U6 snRNA (RNA pol III). Why this specialization exists remains a bit mysterious, though once it started there was no going back. In any case, it happened and is totally characteristic of eukaryotes, so these duplications (which involve the duplication of numerous genes encoding proteins of the polymerase complex itself and its regulators and way-finding helpers) can be used to date eukaryogenesis, using a very carefully calibrated and species-sampled molecular clock. And what they find is that all of these duplications, given as ranges in the diagram below, with green dots at the likeliest time point, all lie prior to the point of "mFECA", which is the mitochondrial first common ancestor, at roughly 2.2 billion years ago. Tabulated over studies of almost a hundred other genes that are similarly duplicated and characteristic of eukaryotes, the authors place the "nFECA", or nuclear eukaryotic common ancestor at almost 3 billion years ago. 

That is a very long time! It is a very long time ago that the characteristics of eukaryotes started to come together, and that is also a very long time (well over a billion years) over which that development spanned before culminating in the last common ancestor of all extant eukaryotes, which the authors put at about 1.7 billion years ago. And note that that still comes a billion years before the cambrian explosion of animal life. We are talking about really deep time here. 

If mitochondrial symbiosis came later, (causing another bout of genomic change as hundreds of bacterial genes moved from the symbiont to the nucleus), just as the atmosphere was getting oxygenated, what was going on in the preceding billion years? One can speculate that these evolving proto-eukaryotes were the top predators of their world, a bit like eukaryotic protists in microbial environments today. The competition would as always have been intense, but there were no higher life forms (i.e. animals or protists) to worry about. Size was not a problem, but rather an advantage. The focus was on quality and effectiveness in finding, disabling, and digesting prey. Thus there was little downside to complexity, unlike the constraints on prey species, which had to optimize for rapid growth and reproduction under both nutrient and predation constraints. New and costly systems for protein secretion, for prey digestion, and intelligent, responsive regulation of all cell processes might have been consistently advantageous.

I take this work as being definitive, at least in terms of setting the debate about early vs late symbiosis. It benefits from a clear theoretical basis and new, vouminous data from appropriately related species in its molecular comparisons. I recommend it highly, as I can only touch on its analysis. The advent of mitochondria was then a later step change in complexity, but brought incredible metabolic productivity that, at least in oxygen-rich environments, would have definitively superceded all the prior forms of the proto-eukaryote, and (unfortunately for us) erased that record of evolution. Another later innovation, between mFECA and the last eukaryotic common ancestor "LECA" was meiosis

One more sample from the author's presentation of molecular duplications that help time eukaryogenesis. Here, DNA repair proteins are emphasized, including some involved in meiosis (light blue dots, see legend). Some of these duplications involve genes from the mitochondrial endosymbiont, (MSH4), and some (such as EME1/2 and MUS81) come from older repair processes, but later specialized for meiosis. 

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