Giardia protozoa in the small intestine of a gerbil

Studying Giardia to find a creature that all eukaryotes are related to -- our most recent common ancestor. (CDC)

by Ursula Goodenough

I'll take a break from thinking about human nature this week and instead riff on something that's more directly related to what goes on in my lab. I'll be lifting up some recent studies that have given us a whole new understanding of evolutionary history, specifically, the more than 1.5-billion-year history of our kind of creature, the eukaryote.

The studies build on a global project, underway in hundreds of labs, wherein the genomes of numerous eukaryotes are being sequenced and their genes identified and compared, making use of increasingly sophisticated sequencing devices and computational algorithms. As more and more genome sequences have become available, it has become clearer that all present-day eukaryotes share a great many genes, meaning that they must share deep common ancestry.

This has lead to the concept of a unicellular organism called the most recent common ancestor (MRCA) of all eukaryotes, a creature to whom we eukaryotes are all directly related.

Granted that taxonomies are in continuous states of revision, a consensus seems to be building that the eukaryotic MRCA gave rise to five mega-radiations or "super-groups," which each branched into numerous sub-radiations and eventually into countless modern-day species. These five supergoups have lovely if arcane names: the Unikonts (that includes us,) the Plantae, the Chromalveolates (including most marine algae,) the Rhizaria (you've probably never heard of any of them,) and the Excavates, including the two major players in our story.

So what was our ancient MRCA like? Was it simple or complex? Was it similar to any known modern organism, or was it something altogether different?

Insights along these lines have come from studies of the Excavates, an eclectic group of related unicellular eukaryotes that includes a number of parasites, like the trypanosomes that cause sleeping sickness. A particularly intriguing excavate is a human intestinal parasite called Giardia, which some readers may have experienced after drinking from streams during a camping trip -- apparently it's not pleasant. Giardia is unquestionably a eukaryote, but in early studies it was found to have peculiar features: It lacked the mitochondria that are present in most eukaryotes; it lacked a sexual cycle and meiosis; and it had only about 6,000 genes, a low number for eukaryotes. Hence some thought that Giardia might resemble a very early version of the eukaryotic state, with mitochondria and sex added later on in evolution.

This inference fell apart in three stages. First it was discovered that Giardia cells in fact have degenerate forms of mitochondria called mitosomes. It then became evident that unicellular parasites in general have far fewer genes than free-living unicells, presumably because they get much of what they need from their hosts, and hence genes encoding many functions degenerate because natural selection no longer operates to maintain them.

But the biggest surprise was finding that the Giardia genome contains a set of genes-encoding proteins that are used only during the process of meiosis in sexual eukaryotes. Because such genes are present in the other analyzed supergroups as well, this means that the MRCA also engaged in a sexual cycle, fusing two haploid gametes to form a diploid zygote and restoring the haploid state via the elaborate meiotic process.

The MRCA was starting to look quite complex indeed.

Very recent insights have comes from a study of the genome of a second Excavate called Naegleria, a free-living unicell that inhabits the soil, crawling around amoeba-style to eat bacteria, growing flagella to swim to a new destination when the bacteria give out, and, if all else fails, forming a cyst around itself and hanging out until things improve.

Naegleria proves to weigh in with 15,727 genes, right up there with the human (~23,000 genes). Again, the genes involved with meiotic sex are present, albeit Naegleria, like Giardia, has never been observed to engage in sex in the lab. Chandler Fulton, a Naegleri expert and one of the authors of the new report, tells me that he figures that they must be shy.

The authors then went on to do an exhaustive search of numerous published eukaryotic genomes in four of the five supergroups (no Rhizaria genomes are yet available), the search criterion being that if a gene is found in Naeglaria and in at least one other supergroup, it was scored as having been present in the MRCA genome. The result: 4,133 genes, a number that is likely to be well on the low side of the MRCA endowment. The inventoried genes encode all the major protein families found in eukaryotes, including those involved in flagellar and amoeboid motility -- key eukaryotic traits -- and in the regulation of gene expression, including the recently discovered RNA interference system. Genes involved in photosynthesis are absent because this capacity showed up later in the Plantae and Chromalveolates, but most everything else appears to have been in place.

The upshot, then, is that the eukaryotic MRCA was likely to have been as genetically complex, and as versatile, more than 1.5 billion years ago, as are free-living unicellular eukaryotes today.

So where, then, did this eukaryotic MRCA come from? Here, in very much of a nutshell, is how the sequence is starting to look.

1) At some point after the early earth cooled down sufficiently (less than 3.8 billion years ago), an original life-form, possibly quite different from what we're familiar with, emerged from non-life.

2) This life-form underwent evolution until some of its descendents attained the genetic make-up of a prokaryote (the alternative to a eukaryote).

3) The ancestral prokaryote then gave rise to two prokaryotic sub-lineages, the bacteria and the archea, that have continued to evolve to this day.

4) At some point, certain archeal and bacterial cells fused together to form the draft version of a eukaryote, organisms that we can call proto-eukaryotes.

5) The proto-eukaryotes evolved until some of their descendents attained the genetic make-up of the MRCA.

6) There then commenced the more than 1.5 billion-year radiation of eukaryotes from the MRCA into present times, with the bacteria and archea evolving lock-step alongside us.

Details of this sequence are as yet murky if not obscure -- there's a huge amount of early evolutionary history left to understand. But meanwhile, we've come to understand that our MRCA would probably have looked something like some sexy unicellular critter you might find today forging about in the mud.

10:14 - March 24, 2010