For those unfortunate enough to inherit it, sickle cell anemia is a devastating disease. Victims suffer from symptoms like frequent infections, persistent fatigue and bouts of crippling pain. It’s a little surprising to realize all this havoc stems from a single and seemingly minor change in the hemoglobin protein — exchanging one amino acid called glutamate for another called valine. That swap creates a pocket on the surface of the protein that can bind other hemoglobin molecules when oxygen is in short supply.
As sickle cell illustrates, small changes in the amino acid sequence of a protein sometimes cause large changes in its structure and properties. And that’s precisely why a chain of amino acids would be a terrible way to store genetic information. Chains of amino acids in water fold up like origami. If a living organism added more “letters” to its genetic code, it would potentially alter the structure and properties of the molecule it used to store the code completely. What living organisms need, then, is a water-soluble polymer where you can add, exchange or take away subunits without changing the molecule’s key physical properties. There aren’t many good answers to this riddle, but life on Earth has hit on one of them: a polyelectrolyte.
If you look at the structure of DNA (see picture on left), all the nucleotides in the chain are linked by phosphate groups. At the pH in your cells, these phosphate groups are negatively charged, so DNA is a polyelectrolyte — a polymer with subunits that bear a charge when it’s dissolved in water. Those negative charges keep the DNA molecule soluble in water even as you add more units. They also repel each other, preventing the molecule from folding up, and force the interactions between the bases in the two strands to occur as far away from the backbone as possible. Without its negatively-charged backbone, DNA would be unable to serve as the genetic template for life. Swapping a dimethylenesulfone for the phosphate in the backbone, for example, creates a polymer without a charged backbone, and chemists have found that if you do this, you end up with a molecule whose properties change dramatically depending on how many units it contains and what those units are.
None of this means that DNA is the only possible template for life. Far from it. I’d be extremely surprised if extraterrestrial life also used DNA to store its genetic information. But the key point is that you need a polyelectrolyte as long as you have life in liquid water, and in part II we concluded that liquid water has all kinds of great advantages over other solvents. So aliens in other solar systems may not use DNA as the vehicle for their genetic information, but they almost certainly use some kind of polyelectrolyte, although what specifically is open to debate. There are lots of options.
Some of those options, of course, would work better than others. In a now-infamous 2010 Science paper, a group of NASA scientists claimed they had found bacteria that could grow in an arsenic-rich environment by incorporating arsenic into their DNA in place of phosphorus. Their evidence, however, was far from sufficient to demonstrate the bacteria really were using the arsenic in their DNA, and the paper drew a great deal of well-deserved criticism from other scientists. Rosie Redfield at the University of British Columbia has investigated the NASA group’s findings in greater detail, and she’s been blogging about her progress at RRResearch (see sidebar); her results give even more reason to think the NASA group were incorrect. It’s not terribly surprising, either, because DNA with arsenic in its backbone would be rather bizarre. Arsenate esters hydrolyze or break up much faster in water than phosphate esters, and arsenic-backbone DNA would be far too fragile to be useful as genetic material for a living organism.
A similar issue explains why your cells use DNA rather than RNA as genetic material. RNA and DNA are very much alike, but look closely at the two structures below and you’ll notice a key difference:
The RNA has an extra oxygen atom on what’s called the 2′ carbon — and it may not look like it, but that’s actually a big deal. The 2′ oxygen in RNA can serve as a nucleophile, an electron-rich atom looking for an electron-poor atom to keep it company. So the 2′ -OH or hydroxyl group in RNA can actually attack the phosphate group and thereby break the connection holding two nucleotides together. Although this reaction is very slow under normal conditions, it still ensures that RNA breaks down much faster than DNA in water at room temperature, and if you turn up the heat or put them in a strongly basic solution, the difference becomes even more obvious. That’s why your cells use DNA as the repository and RNA as the messenger. When it comes to storing genetic information, you need a polymer that’s going to remain intact for a long time.
Action and Reaction
Chemical reactions are fascinating for many of us, I think, because they can seem both dramatic and mysterious. Let’s say I go into the lab, take some lithium aluminum hydride and mix it with some water in a small beaker. I’m not actually going to do this, of course, because if I did the beaker would blow up. But why would it do that? The molecules in the beaker are just molecules, after all; they don’t have minds of their own. Why do they “want” to react with each other? Why do chemical reactions happen?
If you’ve read part I, you may have already guessed the answer: the Second Law of Thermodynamics.
We know from the Second Law that the total entropy of the universe will always increase (see Part I for more on why this is true). So thermodynamics is like a casino game where the house always comes out on top. You can only decrease the entropy of one object or system by increasing the entropy of another.
Your freezer, for example, decreases the entropy of water in an ice cube tray by cooling it and turning it into ice. But you can get away with this because you expend energy from a power plant to keep your freezer running, and this process causes a much bigger increase in entropy. Likewise, the entropy of a cup of coffee decreases as it cools. But the entropy of the surrounding air increases by a greater amount as it takes up the heat, which is why the cup cools until it and the room are at the same temperature.
So a net increase in entropy can come in one of two ways. The entropy of the system where a reaction takes place could increase, or the reaction could release heat, thereby increasing the entropy of its surroundings. All chemical reactions happen because they do one or both of these things. (I’ll come back to this in Part IV in connection with photosynthesis.)
Ultimately, thermodynamics determines which reactions will happen of their own accord and which ones won’t. But it doesn’t tell us how fast those reactions will happen. Thermodynamics predicts, for example, that diamond will tend to spontaneously turn into graphite; but this process is so slow that for all practical intents and purposes it’s not happening. If you want to wait for your engagement ring to turn into pencil lead, you’ll have to wait a long time. So even though thermodynamics is central to chemistry in the sense it dictates what happens, by itself it’s not sufficient to make predictions, because we also need to know how fast reactions happen.
This is where a catalyst comes in handy. A catalyst is a substance or compound that speeds up a reaction. No catalyst can violate the Second Law, however; it can only speed up a reaction if that reaction is something that would happen anyway. But there’s a huge difference between a reaction that takes decades and a reaction that happens in real time. And that’s why catalysts are essential to life; indeed, no organism could continue to live or maintain itself without catalysts. The catalysts your cells employ are proteins called enzymes.
Could E.T. employ some other kind of molecule in place of an enzyme to speed up reactions? Perhaps; but life doesn’t just need catalysts, it needs highly selective catalysts, catalysts that speed up specific reactions and can be modified to turn the catalyst on or off as needed. A huge number of reactions take place in a cell, and the cell needs to regulate them and make things happen at the right time.
Like all other proteins, enzymes are chains of amino acids, and the properties of the amino acids in that chain cause it to fold up like an origami figurine and assume a specific shape. This shape is critical to its function, because it determines what kinds of molecules the enzyme can grab, just as the shape of a lock determines what kind of key will fit. So it results in a catalyst that is highly efficient and highly selective. By employing amino acid chains, the cell also ensures all the enzymes it needs can be made from the same basic building blocks, and enzymes can be assembled and taken apart using standard machinery.
These clear advantages strongly suggest life forms on other planets also employ polymer catalysts — in fact, it’s difficult to see what else they could use. What kind of polymer is a tougher question. Terran enzymes/proteins are all polyamides, meaning the subunits are joined by an amide bond. Polyesters would be inferior by far, because the polyester backbone lacks some of the properties that cause proteins to fold. We can’t definitely assume E.T. uses polyamides, however, because we can think of other things like sulfonamides that would be interesting too. Likewise, we don’t know E.T. necessarily uses amino acids, and even if E.T. does, there’s no reason to assume E.T. relies on the same 20 you and I use. But polymer catalysts definitely and probably a polyamide of some kind or another is my bet, assuming we’re talking about life in liquid water.
In the next post: Why life elsewhere in the universe probably relies on sunlight just like us — and why we’ll never be able to meet alien life to find out whether I’m right anyway.
Steven A. Benner, Daniel Hutter, Phosphates, DNA, and the Search for Nonterrean Life: A Second Generation Model for Genetic Molecules, Bioorganic Chemistry, Volume 30, Issue 1, February 2002, Pages 62-80, ISSN 0045-2068, 10.1006/bioo.2001.1232.
Tackett, A. (2002). Non-Watson-Crick interactions between PNA and DNA inhibit the ATPase activity of bacteriophage T4 Dda helicase Nucleic Acids Research, 30 (4), 950-957 DOI: 10.1093/nar/30.4.950
