According to the theory put forward by Cavalier-Smith as long ago as 1983, some of the simple single-celled eukaryotes living today do still resemble the earliest eukaryotes. More than a thousand species of primitive eukaryotes do not possess mitochondria. While many of these probably lost their
mitochon-Quest for a Progenitor 41
dria later, simply because they didn’t need them (evolution is always quick to jettison unnecessary traits), Cavalier-Smith argued that at least a few of these species were probably ‘primitively amitochondriate’—in other words, they never did have any mitochondria, but were instead primitive relics of the age before the eukaryotic merger. To generate their energy, most of these cells depend on fermentations in the same way as yeast. While a few of them tolerate the presence of oxygen, most grow best at very low levels or even in the complete absence of the gas, and thrive today in low-oxygen environments.
Cavalier-Smith named this hypothetical group the ‘archezoa’ in deference to their ancient roots and their animal-like, scavenging mode of living, as well as their similarities to the archaea. The name ‘archezoa’ is unfortunate, in that it is confusingly similar to ‘archaea’. I can only apologize for this confusion. The archaea are prokaryotes (without a nucleus), one of the three domains of life, while the archezoa are eukaryotes (with a nucleus) that never had any mito-chondria.
Like any good hypothesis, Cavalier-Smith’s was eminently testable by the genetic sequencing technologies then reaching fruition—the capacity to work out the precise sequence of letters in the code of genes. By comparing the gene sequences of different eukaryotes, it is possible to determine how closely related different species are to each other—or conversely, how remote the archezoa are from more ‘modern’ eukaryotes. The reasoning is simple. Gene sequences consist of thousands of ‘letters’. For any gene, the sequence of these letters drifts slowly over time as a result of mutations, in which particular letters are lost or gained, or substituted one for another. Thus, if two different species have copies of the same gene, then the exact sequence of letters is likely to be slightly different in the two different species. These changes accumulate very slowly over millions of years. Other factors need to be considered, but to a point the number of changes in the sequence of letters gives an indication of the time elapsed since the two versions diverged from a common ancestor. These data can be used to build a branching tree of evolutionary relationships—the universal tree of life.
If the archezoa really could be shown to be among the oldest of eukaryotes, then Cavalier-Smith would have found his missing link—a primitive eukaryotic cell, that had never possessed any mitochondria, but which did have a nucleus and a dynamic cytoskeleton, enabling it to change shape and feed by phago-cytosis. The first answers became available within a few years of Cavalier-Smith’s hypothesis, and apparently satisfied his predictions in full. Four groups of primitive-looking eukaryotes, which not only lacked mitochondria but also most other organelles, were confirmed by genetic analysis to be amongst the oldest of the eukaryotes.
The first genes to be sequenced, by Woese’s group in 1987, belonged to a tiny
42 The Origin of the Eukaryotic Cell
parasite, no larger than a bacterium, which lives inside other cells—indeed, can only live inside other cells. This was the microsporidium V. necatrix. As a group, the microsporidia are named after their infective spores, all of which come replete with a projecting coiled tube, through which spores extrude their con-tents into a host cell, then multiply to begin their life cycle afresh, ultimately producing more infective spores. Perhaps the best-known representative of the microsporidia is Nosema, which is notorious for causing epidemics in honeybees and silkworms. When feeding inside the host cell, Nosema behaves like a minute amoeba, moving around and engulfing food by phagocytosis. It has a nucleus, a cytoskeleton and small bacterial-style ribosomes, but has no mitochondria or any other organelles. As a group, the microsporidia infect a wide variety of cells from many branches of the eukaryote tree-of-life, including vertebrates, insects, worms, and even single-celled ciliates (cells named after their tiny hair-like
‘cilia’, used for feeding and locomotion). As all microsporidia are parasites that can survive only inside other eukaryotic cells, they can’t truly represent the first eukaryotes (because they would have had nothing to infect) but the diverse range of organisms that they do infect suggests that they have ancient origins, going back to the roots of the eukaryotic tree. This assumption seemed to be confirmed by genetic analysis, but there was a catch, as we shall see in a moment.
Over the next few years, the ancient status of the three other groups of primitive eukaryotes was confirmed by genetic analyses—the archamoebae, the metamonads, and the parabasalia. All three groups are best known as parasites, but free-living forms do also exist, perhaps fitting them better than the microsporidia as the earliest eukaryotes. As parasites, these three groups occasion much misery, illness, and death; how ironic that these repellent and life-threatening cells should be singled out as our own early ancestors. The archamoeba are best represented by Entamoeba histolytica, which causes amoebic dysentery, with symptoms ranging from diarrhoea to intestinal bleed-ing and peritonitis. The parasites burrow through the wall of the intestine to gain access to the bloodstream, from where they infect other organs, including the liver, lungs, and brain. In the long term, they may form enormous cysts on these organs, especially the liver, causing up to 100 000 deaths worldwide each year. The other two groups are less deadly but no less smelly. The best-known metamonad is Giardia lamblia, another intestinal parasite. Giardia does not invade the intestinal walls or enter the bloodstream, but the infection is still thoroughly unpleasant, as any travellers who have incautiously drunk water from infected streams know to their cost. Watery diarrhoea and ‘eggy’ flatu-lence may persist for weeks or months. Turning to the third group, the parabasalia, the best known is Trichomonas vaginalis, which is among the most prevalent, albeit least menacing, of the microbes that cause sexually trans-mitted diseases (though the inflammation it produces may increase the risk of
Quest for a Progenitor 43
contracting other diseases such as AIDS). T. vaginalis is transmitted mainly by vaginal intercourse but can also infect the urethra in men. In women, it causes vaginal inflammation and the discharge of a malodorous yellowish-green fluid.
All in all, this portfolio of foul ancestors just goes to prove that we can choose our friends but not our relatives.