The problem is that our genome is constantly bombarded by potentially damaging stimuli in our environment. We sometimes think of this as a modern phenomenon, especially when we consider radiation from disasters such as those at the Chernobyl or Fukushima nuclear plants. But in reality this has been an issue throughout human existence. From ultraviolet radiation in sunlight to carcinogens in food, or emission of radon gas from granite rocks, we have always been assailed by potential threats to our genomic integrity. Sometimes these don’t matter that much. If ultraviolet radiation causes a mutation in a skin cell, and the mutation results in the death of that cell, it’s not a big deal. We have lots of skin cells; they die and are replaced all the time, and the loss of one extra is not a problem.
But if the mutation causes a cell to survive better than its neighbours, that’s a step towards the development of potential cancer, and the consequences of that can be a very big deal indeed. For example, over 75,000 new cases of melanoma are diagnosed every year in the United States, and there are nearly 10,000 deaths per year from the condition.{27} Excessive exposure to ultraviolet radiation is a major risk factor. In evolutionary terms, mutations would be even worse if they occurred in eggs or sperm, as they may be passed on to offspring.
If we think of our genome as constantly under assault, the insulation theory of junk DNA has definite attractions. If only one in 50 of our base pairs is important for protein sequence because the other 49 base pairs are simply junk, then there’s only a one in 50 chance that a damaging stimulus that hits a DNA molecule will actually strike an important region.
It’s also consistent with why the human genome contains so much junk DNA compared with the relatively tiny amounts present in less complex species such as the worm and yeast, as we saw in Figure 3.1. Worms and yeast have short life cycles, and can produce large numbers of offspring. The cost — benefit equation for them is different from that of a species such as humans, who take a long time to reproduce and only have small numbers of offspring. For worms and yeast there probably isn’t much point putting a large amount of effort into protecting the protein-coding genes so extensively. Even if a few of their offspring carry mutations that make them less fit for their environment, the majority will probably be OK. But if you get very few shots at passing your genetic material on to the next generation, protecting those important protein-coding genes makes good evolutionary sense.
Nature, as we have seen, is nothing if not adaptive, and so even though the insulation theory makes good sense, it raises another couple of questions. Is insulation the only role of junk DNA?; and where did all this insulating material come from in the first place?
4. Outstaying an Invitation
Every British schoolchild knows the date 1066. It’s the year that William the Conqueror and his troops from Normandy in what is modern-day France invaded England. This wasn’t some temporary raiding party. The invaders stayed, brought their families over and expanded in numbers and influence. They ultimately assimilated, becoming an integrated part of the English political, cultural, social and linguistic landscape.
Every American schoolchild knows the date 1620. It’s the year that the Mayflower anchored at Cape Cod, triggering the great wave of European migration and settlement to North America. Like the Normans in Britain over 500 years before them, these early settlers expanded in numbers rapidly, altering the landscape forever.
A similar event happened in the human genome many millennia ago. It was invaded by foreign DNA elements, which then multiplied hugely in number, finally becoming stable integral parts of our genetic heritage. These foreign elements act as a kind of fossil record in our genome, which can be compared with the records from other species. But they also can affect the function of our protein-coding genes, influencing health and disease.
Although they can affect expression of protein-coding genes, these foreign elements don’t code for proteins themselves. This makes them an example of junk DNA.
When the draft human genome sequence was released, it was astonishing to realise just how widely these genetic interlopers have spread through our DNA.{28} Over 40 per cent of the human genome is composed of these parasitic elements. They are called interspersed repetitive elements, and there are four main classes.[1] As their name suggests, they are DNA stretches in which particular sequences are repeated. The sheer numbers are extraordinary. There are over 4 million of these interspersed repetitive elements in the human genome. One class alone is present 850,000 times throughout the genome and constitutes over 20 per cent of our DNA.
Most of these sequences found ways in the past of increasing their numbers within the genome. Often they mimicked the action of certain types of viruses, similar to the virus that causes AIDS. The basics of this are shown in Figure 4.1. It provides a mechanism whereby a cellular sequence can be copied over and over again and reinserted back into the genome. This creates an amplification cycle that results in the repetitive sequences increasing in number faster than the rest of the genome.
Figure 4.1 A single DNA element is copied to create multiple RNA copies. In a relatively unusual process, these multiple RNA molecules can be copied back into DNA and reinserted into the genome. This amplifies the number of these elements. This may have happened multiple times in early evolution, but just one round is shown here for clarity.
In many ways, the repeats have undergone the equivalent of copy-and-paste in the genome. This is what has allowed them to spread all over our chromosomes.
As a consequence of these amplifications, we carry enormous numbers of these elements in our genome. The question is whether or not this actually matters. Do these sequences have any effect, or are they just passengers in the genome, with neither positive nor negative impacts?
There are various ways in which we can consider this question. Most of the repeats are very old in evolutionary terms. Comparisons with other animals show that the majority of the repeats arose before placental mammals separated from other animal lineages, over 125 million years ago. For at least one of the classes of repeats, we haven’t developed any new insertions since we separated from the Old World monkeys about 25 million years ago. So there seems to have been a huge expansion in repeats in the human genome in our distant past. After that, the numbers didn’t increase significantly, which might suggest that there is an upper limit to the number of these repeats we can tolerate. But they also seem to be cleared out of the genome very slowly, which in turn suggests that as long as the number of repeats is below this limit, we can put up with them.
And yet there does seem to be some difference in the ways that the human genome copes with such repeats, compared with other species. Mammals in general seem to have a more diverse range of certain repeats than other species. But in mammals, these are based on very ancient sequences that have stuck around for a long time. In other organisms, the old repeats have been cleared out to some extent, and newer ones have taken their places. The authors of the draft human genome sequence calculated that in the fruit fly, a non-functional DNA element has a half-life of about 12 million years. In mammals, the half-life is about 800 million years.
But even among mammals, humans seem to be unusual. Repeat elements have been decreasing in number in the hominid lineage since the expansion in the number of mammalian species. This hasn’t happened in rodents. The majority of the repeats in the human genome also no longer undergo copy-and-paste. Essentially, the repeats are more active in rodents than in primates.
1
The four classes are known as SINES (short interspersed repetitive repeats); LINEs (long interspersed elements); LTRs (elements with long terminal repeats); DNA transposons.