It’s a little as if our protein-coding genome has been built from a giant LEGO kit. Most LEGO kits, especially the large starter boxes, contain a selection of bricks that are variations on a small number of themes. Rectangles and squares, some sloping pieces, perhaps a few arches. Various colours, proportions and thicknesses, but all basically similar. And from these you can build pretty much all basic structures, from a two-brick step to an entire housing development. It’s only when you need to build something extremely specialist, like the Death Star, that it’s necessary to have very unusual pieces that don’t fit the basic LEGO templates.
Throughout evolution, genomes have developed by building out from a standard set of LEGO templates, and only very rarely have they created something completely new. So we can’t explain human complexity by claiming we have lots of unusual human-specific protein-coding genes. We simply don’t.
But where this all becomes odd is when we compare the size of the human genome with that of other organisms. Looking at Figure 3.1, we can see that the human genome is much bigger than that of C. elegans and much, much bigger than that of yeast. But in terms of numbers of protein-coding genes, there isn’t anything like as great a difference.
Figure 3.1 In the upper panel, the areas of the circle represent the relative sizes of the genomes in humans, a microscopic worm and single-celled yeast. The human genome is much bigger than those from the simpler organisms. The lower panel represents the relative numbers of protein-coding genes in each of the three species. The disparity here between humans and the other two organisms is much less than in the top panel. The large relative size of the human genome clearly can’t be explained solely in terms of numbers of protein-coding genes.
These data demonstrated convincingly that the human genome contains an extraordinary amount of DNA that doesn’t code for proteins. Ninety-eight per cent of our genetic material doesn’t act as the template for those all-important molecules believed to carry out the key functions of a cell or an organism. Why do we have so much junk?
One possibility is that the question is irrelevant or inappropriate. Maybe the junk has no function or biological significance. It can be a mistake to assume that because something is present, it has a reason to be there. The human appendix serves no useful purpose; it’s just an evolutionary hangover from our ancestral lineages. Some scientists speculated back in 2001 that this might also be true of most of the junk DNA in the human genome.
Part of the rationale for this suggestion lay in an interesting animal, the pufferfish (also known as the blowfish). Pufferfish are remarkable creatures. Because they are slow, clumsy swimmers they are unable to evade predators. If faced with a threat, they rapidly take in huge amounts of water and swell up into a globe, which in some species is covered in spikes. If that isn’t enough to deter a hungry predator, they also contain a toxin which is over a thousand times more powerful than cyanide. This has given the pufferfish a weird notoriety. In Japan it is considered a delicacy (called fugu), but one with a highly chequered history, since inexpert preparation can carry lethal consequences for the diner.
Genetics researchers were very fond of pufferfish, or at least its DNA. The genome of a particular pufferfish called Fugu rubripes is the most compact of any vertebrate. It is only about 13 per cent of the length of the human sequence, but it contains pretty much all the usual vertebrate genes.{25} The reason the pufferfish genome is so small is because it doesn’t contain very much junk DNA. In the days when it cost a lot of money to sequence DNA, pufferfish was a very useful species to use when comparing genomes from different organisms. And because its genome contains so little junk, it was relatively easy to identify individual genes, because there weren’t the signal-to-noise issues that were such a problem when annotating the human genome. Scientists were able to spot genes in Fugu rubripes very easily, and then use the sequence data to help them search for similar genes in noisier genomes such as our own.
Because pufferfish have very little junk DNA but are functional and successful organisms, it was suggested that the non-coding regions of the human genome might be ‘simply parasitic, selfish DNA elements that use the genome as a convenient host’.{26} But this isn’t necessarily a logical projection. Just because something has no apparent function in a specific organism, it doesn’t mean it is irrelevant in all species. Because evolution is usually building from a relatively limited repertoire of components (remember the LEGO set), there is a tendency for features to be co-opted for new functions. So, junk DNA could easily have roles in other organisms, especially ones that are more complex.
It is also worth bearing in mind that there is a functional cost for a cell in containing so much junk DNA. Humans all start life as one cell, formed when an egg fuses with a sperm. That single starting cell divides to form two cells. The two cells divide to form four, and the process continues. An adult human is composed of about 50–70 trillion cells. That’s a lot of cells to visualise, so try it this way. If each cell was a dollar bill, and we stacked 50 trillion dollar bills on top of each other, they would stretch from the Earth to the moon and halfway home again.
It takes about 46 cycles of cell division, at a minimum, to create that many cells. And every time a cell divides, it first has to copy all its DNA. If less than 2 per cent of the DNA is important, why would evolution maintain the other 98 per cent if it is simply functionless junk? As we have already acknowledged, the greatest evidence in favour of evolution of species lies in all those things we are stuck with because of our forebears (such as the appendix). But using huge amounts of resources to reproduce 49 ‘useless’ base pairs for every one that performs a function seems like taking redundancy a bit far.
One of the first theories for why the human genome contains so much DNA arose even before the draft human genome sequence had been completed, when researchers already recognised that there was a significant part of our genome that didn’t code for protein. It’s the insulation theory.
Imagine you own a watch. Not just any old watch, but a phenomenally expensive watch such as a vintage Patek Philippe of the type that sells for a couple of million dollars. Now imagine there is a large and very angry baboon in the vicinity, carrying a really heavy stick. You have to put your watch in a room and you are given a choice. You can’t stop the baboon going into any of the rooms, but you can decide on the room where you want to leave the watch. The choices are:
A. A small room with nothing else in it but a table, on which you have to leave the watch.
B. A large room containing 50 rolls of loft insulation, each roll being 5m in length and 20cm deep, and you can hide the watch deep in any one of the 50 rolls.
It’s not that difficult to work out which to choose to maximise the chances of the watch escaping damage, is it? And the insulation theory of junk DNA was built on the same premise. The genes that code for proteins are incredibly important. They have been subjected to high levels of evolutionary pressure, so that in any given organism, the individual protein sequence is usually as good as it’s likely to get. A mutation in DNA — a change in a base pair — that changes the protein sequence is unlikely to make a protein more effective. It’s more likely that a mutation will interfere with a protein’s function or activity in a way that has negative consequences.