Recent data have shown that there is significant interaction between the systems in our cells that try to regulate and respond to energy and metabolism fluctuations, and those that maintain genomic integrity, including telomere stability.{80} It’s unsurprising, therefore, that scientists have analysed the lengths of telomeres in cells from obese individuals. The same paper that examined the effects of smoking on telomere length also looked at the effects of obesity. They found that the telomere shortening associated with obesity was even more pronounced than for smoking, equating to nearly nine years of life.{81}
If all this inspires you to keep your weight under control, choose how you do this rather carefully. According to the United Nations, the country with the highest percentage of people who are aged 100 or over is Japan.{82} The traditional Japanese diet almost certainly plays a role in this, because Japanese people who have changed to a Western diet develop Western chronic diseases. The traditional diet is based on low protein intake and relatively high carbohydrate levels. Studies in rats also showed that a low-protein diet early in life was associated with increased lifespan, which in turn was associated with long telomeres.{83}
So if you’re thinking of adopting the high-protein and low-carb Atkins or Dukan diets, have a little word with your junk DNA first. I suspect your telomeres might say no.
6. Two is the Perfect Number
One cell becomes two; two become four; four become eight and, to quote from The King and I, ‘et cetera, et cetera, and so forth’{84} until there are over 50 trillion cells in a human body. Every time a human cell divides, it has to pass on exactly the same genetic material to both daughter cells as it contains itself. In order to do this, the cell makes a perfect copy of its DNA. This results in a replicate of each chromosome. The two replicates stay attached to each other initially, but then are pulled apart to opposite ends of the cell. A basic schematic for this is shown in Figure 6.1.
Figure 6.1 A normal cell contains two copies of each chromosome, one inherited from each parent. Before a cell divides, each chromosome is copied to create a perfect duplicate. The copies are pulled apart when the cell divides. This creates two daughter cells, containing exactly the same chromosomes as the original cell. For simplicity, this figure shows just one pair of chromosomes, rather than the 23 pairs in a human cell. The different colours indicate different origins of the pair, one from each parent. The diagram only shows division of the nucleus, but this is also accompanied by division of the rest of the cell.
The only exception to this is when the germ cells in the ovaries or testes create eggs or sperm. Eggs or sperm only contain half the number of chromosomes that are found in all the other cells of the body. The result of this is that when an egg and a sperm fuse, the full chromosome number is restored in the single cell (the zygote) which will then divide to become two cells et cetera, et cetera and so forth.
This halving of the chromosome number is possible because all our chromosomes come in pairs. We inherit one of each pair from our mother and one from our father. Figure 6.2 shows how the chromosome number is halved when eggs or sperm are created.
If cell division goes wrong, either when new body cells are created or when the germ cells create eggs or sperm, the effects can be really serious, as we will see later in this chapter. Cell division is an exceptionally complex process, involving hundreds of different proteins working in a highly coordinated fashion. Given how complicated it is, and how vital it is that cell division happens smoothly and successfully, it might seem surprising that quite a lot of it is critically dependent on a long stretch of junk DNA.
This particular stretch of junk DNA is called the centromere, and unlike the telomeres from the last chapter, the centromere is found on the interior of a chromosome. Depending on the chromosome, it may be pretty much in the middle, or it may be near to an end. Its position is consistent in the sense that on human chromosome 1, for example, it’s always near the middle whereas in human chromosome 14 it’s always near the end.
Centromeres are essentially attachment points for a set of proteins that drag the separated chromosomes to opposite ends of the cell. Imagine Spider-Man is standing in a set position and needs to get something. He throws a web at the thing he wants, and then drags it to him. Now imagine that a very tiny Spider-Man is standing at one end of a cell. He throws a web at the chromosome he wants, the web attaches, and he pulls the chromosome to his end of the cell. A tiny Spider-Man clone does the same thing at the opposite end of the cell for the other chromosome in the matching pair.
Figure 6.2 This shows the cell division process that generates gametes (eggs or sperm) each containing just one of every pair of chromosomes. The process initially looks like the standard cell division shown in Figure 6.1. However, this is followed by a second separation of chromosome pairs, to create gametes with only half the normal number of chromosomes. There is also an early event where genetic material is swapped over within chromosome pairs, to create greater genetic diversity in offspring, but this isn’t shown in this figure.
There is a complication for Spider-Man. Most of the surface of the chromosome is coated with web-repellent. There is only one part where his web will stick. This part is the centromere. In the cell the centromere attaches to a long string of proteins which pulls the chromosome away from the centre and to the periphery. This string of proteins is called the spindle apparatus.
Centromeres play a very important and consistent role in all species. They form the essential attachment point for the spindle apparatus. It’s essential that this system works properly, or cell division goes wrong. Given that this is such a vital process, we would expect that the centromere DNA sequence would be highly conserved throughout the evolutionary tree. But weirdly, this isn’t the case at all. Once we move beyond yeast[9] and microscopic worms,[10] the DNA sequence is highly variable when we look at different species.{85} In fact, the DNA sequence of a centromere may differ between two chromosomes in the same cell. This level of sequence diversity, in the face of functional consistency, is really quite counterintuitive. Happily, we are starting to understand how this vital region of junk DNA manages to pull off this strange evolutionary trick.
In human chromosomes, the centromeres are formed from repeats of a DNA sequence that is 171 base pairs in length.[11] These 171 base pairs are repeated over and over, and may reach lengths of up to 5 million bases in total.{86} The critical feature of the centromere is that it acts as a location for the binding of the protein called CENP-A (Centromeric Protein-A).{87} The CENP-A gene is highly conserved between species, in contrast to the centromere DNA.
Our Spider-Man analogy might be useful again here in terms of understanding the apparent evolutionary conundrum we laid out earlier. Spidey’s web can bind to CENP-A protein. It doesn’t matter if the CENP-A protein is bound to meat, bricks, potatoes or lightbulbs. So long as the CENP-A protein is bound to something, Spider-Man’s web will stick to it, and pull the CENP-A and the something towards our superhero.