They say that size doesn’t matter, but try telling that to bacteria. Most are very small, for they rely heavily on passive diffusion to ferry important nutrients and molecules across their membranes. To ensure that this happens quickly enough, bacteria need to ensure that their surface area is large enough relative to their volume – become too big and they won’t be able to import enough nutrients to support their extra size.
These constraints greatly limit the size of bacteria. The larger ones solve the problem by being extremely long and slender, or by using an internal compartment called a vacuole to push their insides to their outer edges. But even these solutions have their limits, and the simple fact is that most bacterial cells are far smaller than those of the more complex eukaryotes – a group that includes all known animals, plants and fungi.
But one group of bacteria – Epulopiscium sp. – flouts this rule. It has developed a genetic trick that allows it to grow to (relatively) gigantic proportions. While a typical bacterium like Escherichia coli is a mere 2 micrometers long, Epulopiscium can grow up to a length of 300 micrometers. That’s not much smaller than the full stop at the end of this sentence and certainly comparable to most eukaryotic cells. And the secret to its mammoth size? DNA, and lots of it.
Repetition repetition repetition
Jennifer Mendell from Cornell University studied the Epulopiscium by working in the lab of Esther Angert, who first identified it as a bacterium in 1993. Angert’s lab had previously shown that the colossal bacterium contains a large quantity of DNA concentrated near its membrane, and Mendell wanted to work out how much.
But doing that wasn’t easy. When it comes to choice of home, Epulopiscium redefines the word ‘picky’, for it only lives in the intestines of surgeonfish. Different species colonise different fish and Mendell worked with one that lives only in the guts of the bulbnose unicornfish. While most microbiologists can culture their subjects, Mendell had to collect hers by spearfishing in the Great Barrier Reef and with these samples, she managed to measure the amount of DNA in over 10,000 Epulopiscium cells.
Most bacteria reproduce by splitting in two or budding off daughters but Epulopiscium produces offspring in a way that’s a lot like a live birth. It grows two daughters inside itself, until they fill the mother cell entirely and burst out of it. These larger, mature cells contained about 250 picograms of DNA, while the smaller, immature ones contained about 85 picograms. That’s still a huge amount – a typical human cell only contains about 6 picograms.
It’s unlikely that all that DNA belongs to a single, massive genome because only a small amount is passed onto each daughter. Epulopiscium may be enormous but its genome is fairly standard in size for bacteria – it just has many copies of it.
Mendell demonstrated this by measuring the frequency of three bacterial genes that are always found once per genome. She found that the large cells contained an average of 41,000 copies of each of these genes for every 156pg of DNA, implying that every cell contained tens of thousands of genome facsimiles! This strategy of having more than two copies of the same genes (as humans do) is known as “polyploidy“.
Mo’ genomes, mo’ proteins
What use could the bacterium have for so many copies of its genome? Mendell offers several answers. For a start, the multiple copies allow it to tolerate significant genetic mutations that would kill most other bacteria. Having more genetic material also allows a cell to become much larger, and being big has its advantages. The bacterium can travel to parts of the gut that are richest in food, and it’s so large that predatory cells that would eat lesser bacteria find it too large a mouthful.
Epulopiscium‘s lifestyle also provides a clue. It is a symbiont, a bacterium that lives in harmony with its fishy hosts. In their intestines, it finds a constant stream of warm, nutritious fluid and in return, it pays its landlord by secreting valuable molecules. If this molecular rent provides the fish with a survival advantage, the bacterium benefits too and will experience a strong evolutionary pressure to provide its host with even more.
And indeed it does – it produces very high numbers of molecular pumps that shuttle proteins out of its borders. The extra genetic material helps it to do that, and Mendell thinks it’s no coincidence that many other symbionts also carry duplicated genomes (albeit not to the same extent).
The bacterium’s extra genetic material is dotted around its edges, near the cell membrane. This means that new proteins can be created and directly fed into the membrane without any transport problems, in the same way that a retailer can minimise shipping delays by having multiple warehouses dotted around a region rather than a single central depot. This division of labour allows a single Epulopiscium cell can act as a colony with different parts responding independently to local conditions.
Many of these advantages – large size, mobility, defence against predators – are typically found in large eukaryotic cells or even multi-celled organisms. By accumulating thousands of copies of its genomes and redistributing them effectively, Epulopiscium has achieved all of these benefits through a completely different route. It’s another testament to the wondrous diversity and abilities of bacteria.
Reference: Mendell, J.E., Clements, K.D., Choat, J.H., Angert, E.R. (2008). Extreme polyploidy in a large bacterium. Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0707522105
Images: Cells from PNAS; unicornfish from Fishbase;
April 28th, 2008 at 5:18 pm
That is SO COOL!
Great post!!
They have *got* to figure out a way to grow that one in lab… I wanna through mutagens at it and see if it can use all those genome copies like radiodurans.
April 28th, 2008 at 6:50 pm
Is there some mechanism to ensure that each individual copy of the genome is the same as all the others? If not, you could construct an awesome phylogeny of the genomes within the one individual.
If these guys can be cultured they might be the perfect bug for large scale biomanufacturing. Once you figure out how to get 41000 copies of a gene into the cell that is. I wonder what viruses prey on these guys.
April 28th, 2008 at 6:59 pm
I wonder if my landlord would accept molecular secretions?
Great post Ed.
April 28th, 2008 at 7:24 pm
I love how cool stuff like this brings out the mad scientist in everyone. “Let’s chuck stuff at them and see what happens!”
FutureMD – they did this but it was getting late so I didn’t write about it. For each of the three genes they looked at, there was definitely a predominant sequence. But there *were* variants – the vast majority differed from the default sequence in just 1 or 2 positions and all of them were unique.
dnaA was the exception – here they found that a single nucleotide was often deleted. It’s not clear what this deletion does, but it occurs within a chain of 10 adenine residues. These chains are apparently very unstable. They’re not common in bacteria and you’d typically find them in proteins for which variety is a good thing. Here, there’s one smack in the middle of an essential gene. Mendell speculates that the existence of multiple genome copies allows the bacteria to tolerate this genetic feature that would cause massive problems for a species that only carried one copy of its genome per cell.
And Dennis, you keep your secretions to yourself
April 28th, 2008 at 8:02 pm
Wow! That’s totally fucking cool!
April 28th, 2008 at 8:49 pm
dammit! Now I have to re-write my lecture notes about prokaryotes being mostly haploid. Normally, I would let just one exception slide, but 40,000-ploid is too much to ignore.
April 29th, 2008 at 10:17 am
Sequence data is interesting, but what about gene expression? Even we have small variations in our genome all throughout our body simply because cells are replicating, but what makes different parts of us different is that we have hugely different gene expression patterns in our different parts. Do you think this bacteria controls gene expression differentially in different regions? You mentioned that they keep their DNA close to the cell surface so that may indicate some locational/functional interaction, especially if not ALL of their DNA is at the surface…
April 29th, 2008 at 4:07 pm
This little fellas seem to be very efficient at reproduction. The strict dependence on their generic DNA appears to be limiting this effective bugs.
April 29th, 2008 at 6:04 pm
As far as I know, DNA is always anchored to a membrane. That just happens to be the inner nuclear membrane in eukaryotes.
May 4th, 2008 at 12:20 pm
The strategy of having high copy numbers of the genome is not limited to giant bacteria.
One group of protists, such as Oxytricha, have two nuclei. A micronucleus with a diploid genome. And a macronucleus that is nonreproductive and has multiple copies of all the genes and is biosynthetically active.
May 29th, 2009 at 10:00 am
Is there some mechanism to ensure that each individual copy of the genome is the same as all the others? If not, you could construct an awesome phylogeny of the genomes within the one individual.
If these guys can be cultured they might be the perfect bug for large scale biomanufacturing. Once you figure out how to get 41000 copies of a gene into the cell that is. I wonder what viruses prey on these guys.
October 21st, 2010 at 9:53 am
Hi thanks for the report..I have a question though:
From the start you mentioned the energy problem grows with bigger size. But why does having more duplicated DNA materials help solving the issue? You didn’t mention this most important question that you’ve raised.