Simple Ain’t So Simple Anymore

Biology Concepts – prokaryotes, simplicity, complexity, organelles, microcompartments

Newer is better, right? Everything old is simple and plain. Back in the good old days, you had to read a book, but today you can browse the internet and pick from 8000 songs while you drive to the superstore to pick up a Kindle. Today is faster. Better. More complex?

How about living in 1800. Could you catch and kill your dinner with a trap of your own making, followed by gutting and dressing it on the back porch of a house you built with your own hands, while you try to keep your entire family from being eaten or dying from an infected scratch?  Now whose world seems complex!

This same belief has been applied to forms of life. Bacteria are old and simple; we are new and complex. Plants and animals can do millions of things that bacteria can’t, because they are so simple and primitive and we are so high tech, biologically speaking.

But it is a mistake to call bacteria simple or primitive. They may not have all the bells and whistles that eukaryotic (eu - true and karyo = nucleus) cells have, but they have survived much longer than other life forms, and they outnumber us by billions. There are more bacteria in a handful of rich soil than people who have ever lived on Earth. So don’t confuse complexity with success.

A cursory look at bacteria would suggest that they are indeed simple. They are bags of chemicals, without the complex organelles that mark eukaryotic cells. Plus, they're small; the whole organism is just one cell. They have just one chromosome and fewer genes than eukaryotic cells. It would be easy to see them as simple.

Even at the biochemical level prokaryotes (pro = primitive) appear simple compared to eukaryotic cells. Our more modern cells aren’t satisfied with just making more proteins, they also modify many of these proteins, adding carbohydrates, acetyl groups, phosphate groups, sulfur groups, etc. These post-translational modifications (after peptides are translated from mRNA messages) are crucial for different functions and for interactions with messengers and DNA.

The exception here is that less than a decade ago scientists found that many prokaryotes also do some kinds of post-translational modifications, includingphosphorylation and acetylation. Acetylation, the addition of a -COCH₃ group to a molecule, is important in eukaryotic cells for several reasons, not the least of which is in determining which DNA is open to be replicated or transcribed (copied to mRNA).

Data from 2004 was the first to show that prokaryotes can carry out phosphorylation (addition of PO₃ groups) to proteins. What is more, acetylation and phosphorylation are reversible modifications, so an additional layer of complexity is added. Prokaryotic proteins have one function when modified and another when not modified, just like modification of eukaryotic proteins. Sounds like prokaryotes have more going on than we thought.

Prokaryotes are the real success stories of life on Earth. They can do things some things eukaryotes can’t do (more on this next time). Even more amazing, every deficit we have said they have - they can’t do this, they don’t have those – can be seen as a reason they are more amazing.

Prokaryotes are single celled organisms, so they have less specialization. But this means that the cell has to carry out every function that the organism needs. Could your fat cells produce antibodies and kill off protozoan invaders? I think not. We also poke fun at prokaryotes because they don’t have organelles; but this means they have to find a way to do all their chemistry in one big open environment, much more difficult .……….or maybe not.

That classic rule of biology, "eukaryotic cells have organelles and prokaryotic cells don’t," may not be completely true. This would be a big exception.  Evidence shows that many kinds of prokaryotes do have local environments, called microcompartments. We have all been living a lie!

The most studied of the microcompartments is the carboxysome. This hollow shell, first described as far back as 1956, holds enzymes (RuBisCo, see When Amazing Isn’t Enough) that many prokaryotes use for carbon fixation. Photosynthesis is the most obvious type of carbon fixation, where carbon in a gas form (CO₂) is converted to carbon in an organic, solid form (carbohydrates).

RuBisCo is a fairly inefficient enzyme, so sequestering it with its substrate inside a microcompartment works to increase the production of energy. Doesn’t this sound a lot like one of the key reasons for the development of organelles – the bringing together of reagents for increased efficiency of reactions?

But it is not just photosynthetic bacteria (cyanobacteria) that use carboxysomes. Many other autotrophic bacteria (auto = own and troph = food) use carboxysomes to fix carbon during chemosynthesis. Chemoautotrophs, for instance, are organisms that use chemical energy rather than sunlight energy to fix carbon.

In many prokaryotes, the oxidation of hydrogen sulfide or ammonia (a nitrogen containing compound) provides the energy for producing organic carbon; Thiomargarita namibinesis from our posts on giant bacteria uses sulfur for chemosynthesis. But there are also organisms that use the energy from the production of methane to drive carbon fixation. You have undoubtedly had experience with intestinal prokaryotes that produce methane gas (methanogens) – don’t try to say you haven’t.

The carboxysome (as a model of many microcompartments) is not a membrane bound bag as organelles are in eukaryotes. Carboxysomes are more like soccer balls made of protein, but in this case they hold a rigid polyhedral form and don’t get bicycle kicked into a prokaryotic net by Pele.

Each face of the shell is made up of a two dimensional polymer of protein hexagons. However, as architects will tell you, this is a difficult shape to close using only hexagons, even with 10,000 of them, like the typical carboxysome has. Soccer balls and the dome at the Epcot Center use strategically placed pentagonal faces that allow for the turning of the hexagonal faces and a closing of the compartment (see cartoon above).

We have used this hexagonal and pentagonal combination for decades, but it was identified in bacteria less than five years ago. This arrangement is also seen in viral protein coats, as well as in carbon fullerenes, which are superstable carbon nanostructures described in 1985 and named for the inventor of the geodesic dome, Buckminster Fuller.

Could this be the exception – nature stealing an idea from humans? Probably not, I’m guessing Dr. Fuller independently happened upon the same solution that nature had worked out millions of years ago – but it took a heck of an intellect to recognize a good thing.

It might be lucky for us that Fuller’s domes had us looking for this combination in other areas. Carboxysomes are present in up to 25% prokaryotic pathogens (disease causing organisms), and current research is aiming to disrupt the formation of the hexagonal/pentagonal compartments as a way to kill, or at least slow down, the microbes. So many prokaryotic pathogens are developing resistance to traditional antibiotics that a new approach will be heartily welcomed.

There are other microcompartments besides the carboxysome. The bacterium Clostridium kluyveri is proposed to have a metabolosome compartment for the conversion of ethanol into carbohydrates. Furthermore, Salmonella enterica, is capable of producing two different metabolosomes; one for propane-1,2-diol and one for ethanolamine, for conversion of these substrates into energy-containing carbon sources.

The evidence of these additional microcompartments makes one wonder just how many different species of protein shelled microcompartments there may be. To investigate this question, a group from UCLA recently published a study using comparative genomics (comparing genes of similar and dissimilar organisms to find groups of genes of similar function) to point out possible enzyme pathways that may be sequestered in microcompartments.

Their late 2012 study suggests that new types of microcompartments for different types of propanediol metabolism, and the identification of microcompartments in organisms for which they were previously unknown, like mycobacteria. The genomic evidence also suggests new types of protein shells, differing compartments being used for differing variants of enzyme function.

It is in these final examples that we see a more concrete purpose for the microcompartment. During the metabolism of alcohol, propane-1,2-diol, or ethanolamine, a compound called acetaldehyde is formed. This is a toxic product that needs to be converted to acetic acid in rapid order to avoid toxicity to the cell. By isolating the acetaldehyde in the metabolosome, S. enterica improves its own living conditions. This is also important to us humans.

Many Asians and Ashkenazi Jews have a mutation of the acetaldehyde dehydrogenase (ALDH₂) gene that produces the enzyme that rids the body of acetaldehyde after the consumption of alcohol. The mutation produces a poorly functioning enzyme, so acetaldehyde builds up in their systems and causes a facial flushing reaction. If both ALDH₂ genes (one from mom, one from dad) are mutated, the person gets violently ill from consuming ethanol. As you might imagine, populations in which this mutation is prevalent have very low rates of alcoholism.

So we have the exception that prokaryotes are not really without organelles; theirs just look different. Could you guess that the exception goes the other way too? Well, it does. The nucleus of eukaryotic cells works with microcompartments that allow certain things in and out, but keep your DNA inside the nucleus.

The pores of the nucleus (Cells Are Great Multitaskers) are complex openings made up of many proteins. Why? Nuclei could just use receptors to allows certain things in or out, similar to the system used by the cell plasma membrane. But evolution went with a more complex solution.

There is a protein microcompartment called a vault complex that works with the pore complex. This is a highly regulated way of moving RNAs and ribosomes (made in the nucleolus which is inside the nucleus) out of the nucleus, while keeping your DNA inside. I don’t think it is a hard concept to grasp that you cells are happier when your DNA stays inside the nucleus; do you keep your valuables on your front lawn?

Next time we will see how the nucleus, its pore complex, and its microcompartment carriers helped us make the jump from prokaryote to eukaryote. The nucleus is a later evolutionary development, but it still uses a prokaryotic system. This is clue that helps us investigate our cellular family tree.