5
All our efforts to reconstruct the past can only ever give an approximation of what really happened. Well-preserved fossils are spectacular but rare and their discovery can only ever convey a patchy record. History is notoriously inaccurate, depending on the inclinations of the author. Mythologies require sophisticated interpretation. Genetics is no different. It is just another foggy lens through which we try to make sense of times gone by. Bearing that in mind, let us clean the eyepiece and take another look.
In Chapter 3 we saw how DNA from living dogs and wolves was able to reconstruct a plausible genetic relationship between the two. These were inferences from modern DNA but, astonishingly, DNA can survive for thousands of years in fossil bone and teeth. As we will see later, it is often in a pretty bad state. Nonetheless it does give us the chance to examine ancient sequences directly rather by inference. Later on, we will have a closer look at how ancient DNA has helped us follow the evolution of the dog. But before that we need to know a little more about DNA itself.
All genetics depends on mutation, the ultimate source of all variation. DNA changes over time. When a cell divides, its DNA is copied so that each of the two daughter cells contains the full set of genetic instructions. The copying process is astonishingly precise and accurate, and the error rate is minuscule. Editing mechanisms within each cell scan the copies for errors and correct them. But the error rate is not zero. After each cell division, roughly 1 in 1,000 million mutations gets through uncorrected. If the emerging mutation changes a vital component of a gene, then the daughter cell will either malfunction or die. Only extremely rarely will a mutation be beneficial. The most dangerous malfunctions are those that turn normal cells into malignant ones which lose the capacity to restrain their own cell divisions, and they develop into tumours. That is why in some rare diseases, where the DNA editing and correction capacity of cells is faulty, it leads to much higher rates of malignancy.
Fortunately, the majority of DNA copying errors has no consequences whatsoever; first, because the errors don’t occur in important genes, or, second, because they are not passed to the next generation. Only mutations in the germ line, being the cells that go on to form eggs and sperm, are capable of travelling on through time. Even then, the vast majority of sperm never get to fertilise an egg, and, in mammals, most eggs are not fertilised anyway. For these reasons alone, the overwhelming majority of germ-line mutations which occur through faulty copying, even the most potentially damaging of them, are not passed on.
Some mutations, however, do get through to the next generation. Most will not be noticed and have no significant effect on the body, either because they occur in unimportant genes or in the gaps between genes in the long stretches of DNA whose function, if any, is still largely unknown. Here it is worth distinguishing between genes and the rest of our DNA. Genes do something, usually instructing cells how to make proteins. There will be more on this when we take a look at gene mutations that have been found in dogs, but for now we will concentrate on the inconsequential mutations that have no effect, neither good nor bad. Precisely because they are so inconsequential, these unassuming ‘neutral’ mutations are the lifeblood of the sort of genetic reconstructions of past events that we have covered so far. A damaging mutation in a vital gene will disadvantage the individual who carries it. Not necessarily fatally, of course, but enough to put him or her at a slight reproductive disadvantage and thus reduce the prospects of the mutation being passed on to the next generation. Generally, over time, the mutant gene will be eliminated by selection, though not always, as we shall see in pedigree dogs. However, the humble and meaningless mutations that have no effect on anything of great importance will escape the scrutiny of selection and will sail on unmolested through future generations. It is these humble mutations that are the guiding lights that illuminate the history written in the language of the genes.
To explain how mutations are used, in dogs and humans, to date past events like the timing of the transformation from wolf to dog, let us imagine a desert island in the middle of a vast ocean. A young couple arrives in a canoe. For our purposes, it could equally well be a couple of shipwrecked dogs. The island is a paradise, with plentiful fresh water in bubbling streams flowing down from high mountains in the interior. There are coconut palms, shellfish and crabs in the sea and no predators or dangerous animals to disturb the idyll. Everything needed for life is on hand, and the couple start a family. Their children grow up in this cradle of abundance and, ignoring incest taboos for the sake of this exercise, have children with their siblings.
Time passes. The population settles down to a stable total of 1,000. Nobody leaves the island, there is plenty for everybody, and no one else arrives. Until one day a scientist and a research assistant turn up and begin taking a DNA sample from each of the inhabitants. The samples go off to the lab and the sequences are read. A few weeks later the scientist and his assistant, now back home, get the results. What can they deduce about the people on the island from the results? It doesn’t matter all that much which genetic markers we are talking about for this example to work, so let’s keep it simple and imagine that we are working with mitochondrial DNA. The first things the researchers notice is that everyone’s DNA sequence is very similar. Some sequences are identical, and we will call that the ‘core’ sequence of the island. However, about half the people have a sequence that differs at just one DNA base from the core.
DNA sequences are written using a childishly simple alphabet with only four letters. These letters represent simple organic chemicals, or bases, joined together in a linear sequence. Their abbreviations are even simpler : A, G, C and T. Any DNA sequence is a long string of these bases: … CCGGTAA … and so on. A mutation might change a T to an A, making the new sequence read as … CCGGAAA … The language may be child’s play, but the meaning is far from simple, as we will explore further in a later chapter, but not now. Instead we travel back to our island.
Of the 1,000 people who were tested, 500 have the core sequence and 500 have a one-base difference from it, but not all at the same one.
The researchers draw the reasonable conclusion that everybody on the island is ultimately descended from one couple, or rather from one woman, as we are dealing with mitochondrial DNA. Can they tell from the results how long ago the island was settled? To get an answer, we need to agree a very important factor. The mutation rate. That is the rate at which mDNA mutations occur and get passed on. It is going to be an estimate, drawn from other results. The factors which contribute to the estimate are sometimes astonishingly crude.
A common approach is to take two species, say human and chimpanzee, compare their DNA sequences and make an assumption about how long it is since they last shared a common ancestor. In this example the usual figure is 6 million years, based on fossil evidence which, for both species, is extremely flimsy. All genetic dating of past events depends crucially on the accuracy of the mutation rate and that it has remained stable over the period.
Fortunately, the estimates of the mitochondrial DNA mutation rate by the various methods come up with a figure that most are happy to accept. For the segment of mitochondrial DNA that Wayne and Vilà used, the rate is estimated to be one base change every 20,000 years. Mutations occur randomly as cells divide, so we must turn to discussing probabilities. A mutation rate of one per 20,000 years doesn’t mean that no mutations occur until that time has passed. It is an average. It could happen in the first generation or the last or, more likely, somewhere in between. Let us say the time between generations on the island is twenty years. If a quarter of the population has a mitochondrial DNA sequence that is one mutation away from the core, the average number of mutations per person across the whole island is then one quarter. The estimated time from first settlement then becomes the average number of mutations (a quarter) from the core, multiplied by the mutation rate (20,000), which comes to 5,000 years.
Returning to our scientists, they go back to the island to inform the council of elders of their results of the project. They also reveal that the original settlers had come from the mainland far away to the east because that is where they have also found the core mDNA sequence among the inhabitants. After listening politely to the presentation, the elders turn to the scientists and, as I have experienced first-hand, they say, most politely, something like ‘Thank you for your trouble. We knew that all along.’
In my deliberately simplified example we were dealing with just one segment of DNA on an island originally settled by only one couple. No one arrived or left for millennia. It doesn’t get any simpler than that.
Let us now suppose that other things happened on the island. Perhaps half the population died in an earthquake, or the central volcano erupted, destroying the crops, and three-quarters of the people starved, or an epidemic killed 90 per cent of the population. These are the sorts of catastrophes which might have happened in real life. Those events can severely distort our calculations. For instance, and let’s make it extreme, a tsunami kills everybody on the island except a couple who were far out to sea fishing at the time. They survived and, over time, their offspring repopulated the island. In this scenario, the genetic calculations would give the time that had elapsed since the tsunami rather than since the original settlement. The island would have undergone a ‘population bottleneck’. There would be no way of telling, by genetics alone, for how long the island had been settled before the tsunami struck. If we introduce further complexity, like a few boatloads of new arrivals, then all hope of being precise about the original settlement date goes up in a puff of smoke.
Given these unknown and often unknowable factors, I take claims of accurate genetic dating of past events with a large pinch of salt. That does not mean they lack value, but it is a mistake to become a slave to such calculations. We will use the island metaphor again when we come to consider the origins of pedigree dog breeds. Wayne and Vilà also used this kind of calculation to estimate the timing of the wolf–dog transition. The answer was much further back than anyone suspected, between 76,000 and 135,000 years ago.