Life is hard for free-living microbes. Many of them undertake great efforts to obtain their energy, some get it directly from sunlight while others derive it from unusual compounds. To them, living inside an animal gut must be like living in some mythical land of plenty. Consider the luxuries! The lucky resident of a gut (biologists call these permanent inhabitants endosymbionts) never has to worry about food, since the host will take care of a steady, pre-processed supply. The gut is also something like a safe haven for the microbial tenants, since there are less predators about than in the big outside world. Is living inside entrails truly the bacterial equivalent of living in the fictional Land of Cockaigne of which medieval peasants dreamed?
"Luilekkerland" / "Land of Cockaigne" by Pieter Breugel (1567). There is no need to worry about food in the land of Cockaigne, where roasted geese fly and pigs walk around with knives in their backs!
Not so much. Even for gut microbes, there’s no such thing as a free lunch. Since many microbes have a wider repertoire of biochemical tricks up their sleeve than their hosts (seriously, animals are biochemically pretty boring, all we do is break down carbon using oxygen), hosts often take advantage of their their abilities. The champion amongst endosymbionts might be Mixotricha paradoxis. This protist inhabits the gut of some termites and produces enzymes that break down cellulose, the main component of wood. Whether you like it or not, it is by virtue of these little creatures that termites enjoy chewing through your wooden garden shed.
The protist Mixotricha paradoxa, endosymbiont of termites (source). Are those little hairs or ... ?
This feat alone is hardly enough to be a champion of endosymbionts, so why did I call them such? It turns out that the endosymbiont Mixotricha has endosymbionts of its own! When Mixotricha was first described in the 30s, it was noted that the cilia (the little hairs) on its surface were unlike normal cilia. The name of Mixotricha even means something like ‘paradoxical mixed-up hairs’. As microscopy techniques became more advanced in the 60s, Cleveland and Grimstone noted that these hairs were not cilia at all, but bacteria anchored to the body surface of Mixotricha! The Mixotricha take lots of effort to fixate these hair-shaped spirochaetes. In fact, bacillus-like bacteria are found at the ‘root’ of every spirochaete! So ultimately we end up with a Matryoshka set of organisms and endosymbionts, all dependent on each other. Amazing.
But let’s leave termites behind and turn our attention to another insect, the carpenter ant. Carpenter ants are home to another endosymbiont called Blochmannia (no, this does not refer to a period of manic blogging). This bacterium synthesizes a bunch of amino acids and other nutrients, which of course benefit the carpenter ant. Like any endosymbiont, Blochmannia is losing genes at a rapid rate. This is not necessarily a bad thing, since many genes that are required for living in the great wide open, are simply not that useful in an environment where you receive your food in pre-processed chunks.
A worker carpenter ant from Tanzania (Camponotus). Source.
Losing genes is not the only form of gene erosion that these endosymbionts face. Scientists have detected a lot more homopolymers inside genomes of endosymbionts. Homopolymers are long stretches of adenosine nucleotides. Now, when a RNA polymerase comes along to transcribe the gene, it is likely to get confused by the repeated adenosines, causing it to ‘slip’ . When such slippage occurs, the RNA polymerase loses its grip, quite likely missing some bases and changing the reading frame in the process (see picture), producing dysfunctional mRNAs and proteins. But the story doesn’t end here.. Many of these homopolymeric tracts contain -conserved- frameshifts themselves! So what is going on there? Why do endosymbionts like Blochmannia combine these two detrimental features, that would make any gene cry its nucleotides out?
Every three bases of DNA (triplet) code for an animo acid. Now, if the RNA polymerase 'slips' and misses a base, the resulting message will be totally different from the original. If a single base is deleted or inserted, the resulting message is also 'frame-shifted'.Source.
Let’s try to make some sense of this confusing situation. Since the Blochmannia populations in ant guts are relatively small, purifying selection that would normally eliminate homopolymeric tracts (they are rarely observed in free-living bacteria) plays a smaller role. While such a slippery tract is not optimal, it’s certainly not the end of the world. For in-frame tracts of 10-11 adenosines long, slippage is estimated to occur 3%-17 % of the time, producing enough functional transcripts. Now, just like RNA polymerase, DNA polymerase is not that happy with these slippery tracts. So during replication, it is likely that the DNA polyemerase screws up and puts in one adenosine too many or too few, leading to frame-shifts. But precisely because the tract is slippery, some transcripts will accidentaly correct the frameshift, and give a full functional transcript! Blochmannia (and many other endosymbionts) are now in the interesting position that they need the slippery tract in order to at least partially transcribe their genes correctly. But why on earth would the frameshift be maintained (some of them have been conserved for millions of years)? Honestly, I’ve got no clue. The frameshifts don’t generate additional transcripts, so that’s not the solution. Some scientists speculate that the combination of slippery tract and frameshift is a convoluted way of reducing gene expression, since many endosymbionts lack gene regulation capabilities. This really does sound convoluted, so I’m not so sure whether it’s the right explanation.
Returning to the Matryoshka story with which we started: recent evidence suggests that the carpenter ants acquired the Blochmannia from aphids or mealy bugs. Ants are known to herd these insects like cows, living from the honeydew that they produce. So the nutritional symbiosis between ants and aphids, lead to the endosymbiosis of ants and Blochmannia. Wicked. I think it’s safe to conclude that living a endosymbiont’s life, is in no way like living in the Land of Cockaigne. Aside from the funky genome erosion, endosymbionts have to actively assist their host and sometimes have to take care of endosymbionts of their own. Ah well, a medieval peasant can dream right?
Cleveland, L., & Grimstone, A. (1964). The Fine Structure of the Flagellate Mixotricha paradoxa and Its Associated Micro-Organisms Proceedings of the Royal Society of London. Series B, Biological Sciences (1934-1990), 159 (977), 668-686 DOI: 10.1098/rspb.1964.0025
Tamas I, Wernegreen JJ, Nystedt B, Kauppinen SN, Darby AC, Gomez-Valero L, Lundin D, Poole AM, & Andersson SG (2008). Endosymbiont gene functions impaired and rescued by polymerase infidelity at poly(A) tracts. Proceedings of the National Academy of Sciences of the United States of America, 105 (39), 14934-9 PMID: 18815381
Wernegreen JJ, Kauppinen SN, & Degnan PH (2010). Slip into something more functional: selection maintains ancient frameshifts in homopolymeric sequences. Molecular biology and evolution, 27 (4), 833-9 PMID: 19955479
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“The Mixotricha take lots of effort to fixate these hair-shaped spirochaetes.” any idea why? Cellulose digestion? Lignin decomposition?
The spirochaetes confer motility to the Mixotricha. The Mixotricha itself is a flaggelate, but it uses its flagella for steering, instead of movement. The spirochaetes give the Mixotricha the ability to move like a ciliate: including the ability to rapidly turn, change speed and generally gliding along smoothly.