A Computer Scientist’s Guide to Cell Biology, Chapter 1.2: Types of Life

Prokaryotes

At the most basic level, all living organisms can be divided into two categories: eukaryotes and prokaryotes, depending on whether they keep their genetic material sectioned off from the rest of the cell.

Prokaryotes, at first glance, seem like a pretty monotonous lot—bacteria, bacteria, and more bacteria. (To be fair there are also archaea, but they look so much like bacteria that it wasn’t until the 1970’s that people noticed that they were genetically different.) Structurally speaking, prokaryotes are more or less just bags of proteins and genetic material, where the “bag” is a plasma membrane, which, in many prokaryotic cells, is reinforced by a layer of stiff starchy armor called a cell wall. Numerous proteins are anchored in the plasma membrane, and inside is a convoluted soup of proteins, sugars, nucleic acids, and other biomolecules known as the cytoplasm. Prokaryotic DNA takes the form of a simple loop which floats somewhere inside the plasma membrane.

If you look a little closer, though, you’ll find an absolutely unbelievable amount of diversity among prokaryotes. These seemingly simple organisms can be found in every nook and cranny of the planet, from hot springs to ice fields to deep-sea vents, and feed on everything from sunlight to elemental sulfur. In 2006, scientists even discovered some prokaryotes can sense magnetic fields, using chains of tiny magnetic crystals as a sort of rudimentary compass needle.

Perhaps the most famous and most-studied prokaryote is Escherichia coli (E. coli to its friends), a bacterium normally found in the human intestine.

Eukaryotes

Eukaryotes are probably more familiar, at least in the sense that most of the living things you’ve ever seen are eukaryotes. As a rule of thumb, anything you can see with your naked eye is a eukaryote. It’s certainly true that all multi-celled organisms are eukaryotes, but the category also includes a number of single-celled organisms like yeast and amoebas. Despite seeming like they have more in common with their prokaryotic cousins than, say, an elephant, the structure and biochemistry of single-celled eukaryotes like yeast is far closer to that of a pachyderm than to a bacteria.

For a start, eukaryotic cells are big, much more so than prokaryotes. The famous E. coli bacterium, for instance, is about 2 μm long, but a typical mammalian cell is 10–30 μm. It’s like comparing a hamster to a human, or a human to a sixty-foot sperm whale.

Eukaryotes also have a much richer inner life than prokaryotes. Every cell, regardless of whether or not it’s part of a more complex organism, has its own set of internal organs, conveniently enough known as organelles, each one enclosed in its own little plasma membrane. The nucleus, for example, keeps the DNA safe and segregated, mitochondria house all the machinery needed to turn sugars into cellular energy, and the endoplasmic reticulum is a vast factory for protein synthesis, to name a few of the most prominent examples.

Not only is eukaryotic DNA tucked away in its own compartment, there’s also far more of it, stored in a much more complicated way. For a start, we don’t just have a single loop—instead, we have many separate sections of DNA, each one wound around thousands of proteins called histones. Histones are then packed together to form nucleosomes; nucleosomes are compressed into supercoils, and ultimately thousands of supercoils collect into a single large complex known as a chromosome.

All this wrapping is extraordinarily effective. A single human cell is microscopic, but if you took all of its DNA and stretched it out end-to-end, it would make a strand almost six feet long. A multi-cellular organism like you has billions of miles worth of DNA in its body.

As another way of emphasizing the relative complexity of eukaryotes, it’s very possible that a eukaryotic cell’s organelles were once completely independent prokaryote-like creatures. According to the theory of endosymbiosis, smaller prokaryotes once took shelter inside the membranes of their larger cousins, providing some sort of service—photosynthesis, say—in exchange for safety and a share of the cell’s resources. Over time, the symbiotic cells became smaller and more specialized, delegating more functions and shifting more DNA to the host cell until they were reduced to the status of internal organs.

The two biggest candidates for this role are mitochondria and chloroplasts, the site where plants turn sunlight into energy. Even today, these organelles retain scraps of their original genomes, with DNA sequences that use completely different codes than those found in the cells’ nucleus

Multi-cellular Life, Tissues and Signaling

The human body—indeed, most any kind of multi-cellular body—is made up of a staggering variety of different cell types. For instance, red blood cells carry oxygen, muscle cells contract and expand our muscles, and nerve cells carry electrical signals across (comparatively) vast distances. And yet, somehow, they all contain the same exact sequences of DNA.

How does one set of instructions give rise to such a staggering variety of end products?  The answer is surprisingly simple—different cells use different parts of the genome. Some genes, such as those related to DNA transcription or metabolic activity, are active in all cells. Other, more specific sequences are only found in certain types of cells.

In addition to differentiating into different types, cells (even bacterial cells) communicate among each other, a process called signaling.

Viruses

When studying biology, prokaryotes are a good place to start because they are the simplest living things. Eukaryotes, in particular multicellular ones, are relevant because, well, that’s what we are. But we’re not done surveying types of life yet, because there are also the entities that are only sort of alive, such as viruses.

Viruses don’t have plasma membranes, or cytoplasm, or metabolic processes, or any of the other machinery normally involved in keeping a cell alive. Instead, they infect more complex organisms and hijack their inner workings, just as an email virus uses existing programs on an infected machine to propagate.

A typical virus, such as the lambda phage, is made up of only two components—a protein coat, and a strand of DNA or RNA with instructions for how to make said coat. In spite of this simplicity, the lambda phage has a rather interesting life cycle.

When it encounters the right type of host cell, the coat binds to the cell’s plasma membrane and injects its payload of genetic material directly into the cytoplasm. Once it’s there, the host cell has no way of telling the difference between its own nucleic acids and those of the invader. The organelles, whose job it is to make proteins, simply “read” the new code and build the new proteins, using the cell’s own resources to do it.

Just to make matters more confusing for the poor cell, the first thing many of these illicitly produced proteins do is splice the virus’s DNA into one of the host’s chromosomes—-in the case of the lambda phage, the protein that does this is called the lambda integrase. Once the integrase has done its dirty work, the cell continues to grow and reproduce, and as it does so, it passes the viral sequences on to its daughters. Eventually, some environmental signal tells the cells to start copying viral DNA and producing viral proteins as fast as they can. Even as its own processes wither away, the cell continues making new viruses, until it finally bursts and releases thousands upon thousands of viruses to seek new targets.

If we think of DNA as a cell’s source code, then a virus, like the lambda phage, is a sort of self-modifying program. Not only does it hijack the cell’s machinery to make copies of itself, but it permanently changes the original code. Often a phage’s alterations will eventually be corrected by the cell or its descendants, but sometimes non-executable fragments of phage “code” stay in the genome. After millions of years of evolution, our genome is littered with the remains of viral insertions, sequences known as transposons.

Plasmids

Viruses aren’t the simplest possible things that can replicate themselves, however. If a virus is nothing but a bit of DNA or RNA in a protein capsule, a plasmid ditches its shell in favor of existence as a free-floating loop of nucleic acid. Once scooped up by a larger cell, the plasmid takes advantage of the same vulnerabilities as the virus and uses the cell’s own machinery to make new copies of itself.

Plasmids are particularly common in prokaryotes, where they serve as a way for bacteria to swap bits of genetic information back and forth. A common—and troublesome—example of this is the transmission of antibiotic resistances from one species of bacteria to another. Experimental biologists can also exploit the process to quickly introduce genes they are interested in.

Prions

Plasmids may be the simplest things that qualify as “sort of alive,” but there is another type of ultra-simple self-replicating biomolecule out there—prions, mis-folded proteins most famous as the cause of “mad cow disease,[1]” along with a number of similar neurodegenerative diseases such as kuru and Creutzfeldt-Jakob disease.

A normal, “living” copy of something called the major prion protein (PrP) is an important player in the nervous and immune systems. Its exact roles are still unknown, but it’s been connected to circadian rhythm, long-term memory, neural plasticity (the brain’s ability to change and adapt), and the activation of various immune cells. Whatever it does is clearly vital, though—prion diseases inevitably lead to death.

It is possible, however, for healthy PrP (referred to as PrPC, for cellular) to mutate, dramatically changing its three-dimensional structure. The new, misfolded variants (or PrPSc, after one of the earliest known prion diseases, scrapie) proceed to attach themselves to healthy PrPC molecules and somehow twist them into the same misfolded shape. PrPC becomes PrPSc, and both copies are released to infect more proteins. So basically, prions are like zombies—they used to be “living”, healthy proteins, but after mutation, they begin to “bite” other healthy proteins and turn them into more zombies, which go on to “bite” more healthy proteins, and on and on until the brain is nothing but a zombie-infested wasteland.


[1] More properly known as bovine spongiform encephalopathy in cows, and variant Creutzfeldt-Jakob disease in humans unfortunate enough to said cows.