October 2013: The Genetics of Blood Groups
I have been reading a book called “Genome” by Matt Ridley. It is an introduction to genetics, and to human genetics in particular, in twenty three chapters – one for each pair of chromosomes on the human genome – and it explains how genetic fingerprinting works, the genetics behind aging, the genetics of intelligence and the heritability of a variety of different diseases as well as giving a simplified explanation of what a gene actually is. It’s also a wonderful illustration of how learning about one thing in depth can lead one in a variety of different and unexpected directions.
A chromosome, it appears, is a molecule of DNA and a molecule of DNA is a long chain of things called bases (little sub-molecules) coiled together in a double helix (like a spiral staircase with two sets of steps: incidentally there is a staircase of this kind at Dover Castle which was built like that so they could get twice as many soldiers up and down in a hurry). There are only four bases: Cytosine, Guanine, Adenine, and Thymine and so if we only worry about the information in a gene (rather than the chemistry) a chromosome can be thought of as a (very) long list of letters C,G,A and T. The information in our genes is determined by the order of these letters.
A gene is a recipe for making a protein. Proteins, it turns out, are surprisingly complicated molecules made by sticking simpler molecules called amino-acids together and so the recipe is a list of the amino acids that are needed to make the protein in the right order to be stuck together. There are twenty amino acids to choose from and every sequence of three bases on the chromosome gives one amino acid. Proteins come in a wide range of sizes but are typically made up of hundreds of amino acids.
Different proteins do different jobs in the body including (and this is a really clever bit) telling each other when and where to do their particular job. Pretty much everything that is clever about life seems to be done by one protein or another and so having the recipes for the right proteins is vitally important.
We get our genes from our parents. We have two copies of each chromosome and so for each gene we have two protein recipes: one from each parent. Often these will be the same: there are some proteins that you can’t live without and so we share a lot of our genes (recipes for proteins) with each other and with other living things. Sometimes, though, there are differences: occasionally the system for copying chromosomes from one cell to another breaks down and gets a letter wrong, misses one out or even repeats a whole section; this leads to different versions of the same gene. Sometimes this makes no difference at all (several three letter sequences give the same amino acid and so it’s possible to make changes to the DNA that make no difference at all to the protein); sometimes it changes the protein in a fairly minor way that has some effect but doesn’t stop it doing its main job; and sometimes the changes completely transform the protein (interestingly, changing a base has much less impact than missing it out completely).
Many of the differences between people can be explained, at least partly, by these differences in their genes. Sometimes one version of a gene will be better for some reason and will give the person with that gene a better chance of survival. One interesting example of this is in blood groups. I already knew that there were four basic blood groups: A,B,AB and O; and that these were determined genetically. I also already knew that cholera was a disease spread through dirty water that killed large numbers of people where the sewers and water supply got mixed up. What I didn’t know is that the proteins in the blood that make you group A or B (or AB, if you have both) make you less susceptible to getting cholera. The protein in group A blood is better at protecting you from cholera than the protein in group B. At first sight this should mean that blood group B should have died out by now but it hasn’t because if you have both proteins (type AB) then you are even more protected (apparently blood group AB people are almost immune to cholera). In a population that is mostly A, the children of a type B person are likely to be type AB which means that B never quite dies out because, although type B isn’t great at surviving, their children are amazing. This argument doesn’t explain why type O blood has survived but cholera is, of course, not the only disease to have killed people over the centuries and it seems that O blood has some benefits in relation to some other diseases. The amazing thing is that a disease that is not apparently genetic (you can’t inherit cholera from your parents) explains the diversity in a feature that doesn’t appear to have anything to do with it (cholera affects your digestive system, not your blood).
Genetics, genetic testing and genetic engineering are an increasing part of our world with new ideas, developments and inventions often making the news. The genetic code is at once surprisingly simple (only four letters in groups of three to make each amino acid) and reassuringly complex (the sheer length of the code – about 3 billion bases, seventy thousand protein recipes – and the interactions between different proteins under different conditions makes for an almost unlimited set of possibilities to work out). There are lots of questions to do with why we catch diseases, why we’re all different, and how we’ve developed that can be answered (at least partially) using genetics: we live in an amazing time when those questions are beginning to be answered.