Natural Selection and the Human Lineage

Has natural selection shaped the human genome?

Sometimes students, having learned about natural selection in other organisms, balk at the notion that this process was involved in our own origins. Despite this hesitation, there is very strong evidence that our own lineage has been subject to natural selection over its long history leading to our species. One example of this evidence comes from the history of our own amylase genes. The story shares similarities to what we have seen for the dog lineage, but also has some interesting differences.

Unlike dogs, humans have two distinct types of amylase genes. Both types have the same enzymatic function (breaking down starch), but they are produced in different locations in the body. One of the types is produced in the pancreas, just like the equivalent enzyme in dogs. Unlike dogs, however, humans have amylase in our saliva as well. This “salivary” amylase works quickly enough that we perceive starchy foods as sweet when we chew them—the amylase enzyme goes to work on the starch, breaking it down into glucose quickly enough for us to taste it. Studies have also shown that salivary amylase continues breaking down starch right through our stomachs and on into our intestines—thereby increasing the amount of glucose we can extract from foods rich in starch.

As you might expect, the human pancreatic and salivary amylase genes sit side-by-side in our genomes, and show the clear signs of being duplicates of each other.* All mammals have pancreatic amylase genes, but only some, such as humans, have salivary amylase genes. This means that the ancestral state was a single pancreatic amylase gene, and the first duplication event produced a second copy, just like what we have seen for dogs. This doubling of pancreatic amylase would likely have been an advantage and come under natural selection in a similar way to what we have seen for dogs. The fact that humans and other great apes share the same duplication event indicates that this event took place in the common ancestor of these species, and thus on the order of 16-20 million years ago.

Once the two pancreatic amylase genes were present in our ancestral lineage, a second event occurred that altered one of the copies: an endogenous retrovirus inserted into the genome next to one of the copies. (Retroviruses are viruses that insert their own genome into the genome of their hosts as part of their infection cycle. Endogenous retroviruses insert into the genome of reproductive cells, such as eggs or sperm—and once inserted, they can persist at a specific spot in a host genome and be passed down from generation to generation.) This retrovirus insertion event altered the DNA sequence that controlled when and where the amylase protein was made—and instead of being made in the pancreas, the altered copy began to be made in salivary glands instead.** Over time, this new combination (one pancreatic copy and one salivary copy) came under natural selection and replaced the previous version that gave rise to it (two pancreatic copies).

Summing up

So, the story of the human amylase gene cluster thus far shows clear signs of repeated mutations (such as duplications) coupled with natural selection to produce the genes that we see in humans today. Of course, if humans were directly created without common ancestry, there would be no need to create these genes directly and then embed within them the evidence of a convoluted history—yet what we see, time and time again, is the clear evidence of mutation and natural selection. It seems that God was pleased to create this aspect of our biology slowly, through what we perceive as a “natural” process—but of course, what we perceive as “natural” is merely the consistent outworking of God’s ordained and sustained providence that is amenable to scientific investigation. As we became human, and shifted our diet towards agriculture and starchy foods, this God-given mechanism allowed us to take advantage of the shift in our environment.

Previously, we described some of the early steps on the path to the present-day human amylase gene cluster, and the role that natural selection played in the process. Having set the stage, we’re now ready to continue the story—and, as we’ll see, it was a long and winding path from this starting point to arrive at what we see in the present day.

As you will recall, the early evolutionary steps in this process (a) duplicated the original human pancreatic amylase gene, and (b) later changed the activity of one of the copies, such that it was no longer made in the pancreas, but rather in saliva. We further noted that this new variant (which we can abbreviate as “1 pancreas / 1 salivary”) came under selection and replaced the “2 pancreas / 0 salivary” variant that it arose from. Having arrived at this point our ancestors would have had amylase enzyme secreted into the small intestine by the pancreas, but also a new function, amylase secretion from the parotid gland into saliva. This salivary amylase would have provided an advantage in an environment with access to starchy foods, since amylase can break down more starch into glucose with enzymes made in both locations than it can with merely two copies made in the pancreas.

This was not the end of the story, however: the stage was now set for further mutational steps that would also be selected for.

What happens next is more straightforward duplication events, similar to the duplication events we have seen before. This time, however, the duplication copies the newer salivary amylase gene. This duplication results in yet another new variant (1 pancreas / 2 salivary) that is selected for as well, since it is an improvement over the (1 pancreas / 1 salivary) variant it arose from. Later on, there is another duplication that spans both salivary copies to give a combination of 1 pancreas / 4 salivary copies. At this point there are five distinct gene copies, all side by side in the genome, and this variant also replaces the previous version due to selection.

The next stage, however, has a twist. Recall that it was the insertion of a retroviral DNA sequence that originally converted the second amylase gene copy from a pancreas enzyme to a salivary enzyme. This retrovirus sequence was copied along with the rest of this gene when it was duplicated, and at this point is still present in each of the four salivary gene copies. Later, the retrovirus excises itself from one of the four salivary copies (leaving only a small “footprint” behind), reverting it back to production in the pancreas. This results in a new (2 pancreas / 3 salivary) variant. This new variant also comes under selection and replaces the (1 pancreas +4 salivary) variant that it arose from, since the doubling of the pancreas enzyme offers an advantage at this point, even if it comes at the expense of one of the salivary genes. The salivary copy that was converted back to a pancreatic gene retains a “scar” of once having been a salivary gene—with a genetic “there-and-back again” tale to tell.

If this all seems a little convoluted, I don’t blame you—it is convoluted. But that is the point—this is the convoluted history that is written into this region of our genomes. It ably demonstrates that we have been shaped by mutation and natural selection. These are the very same types of mutation and selection events that scientists have observed in real time in experimental organisms, and they demonstrate that random mutation (again, random in the biological sense, as we discussed yesterday) is quite capable of producing new genes with new properties, and that natural selection is able to shift a population over to new, advantageous variants that arise.

And on it goes, even to this day

At this point you might think that the story was over, and that all humans now have the “2 pancreas / 3 salivary” version of the amylase gene cluster. What is interesting is that this is not actually the case. Some humans have even more copies of the salivary amylase genes – individuals with up to a staggering 10 salivary copies side-by-side have been identified. At the other end of the scale, some humans have less than the “standard” 3 copies, perhaps just two or even only one. These variants arose as deletions from the “standard” 2 pancreas / 3 salivary arrangement. In other words, humans are hugely variable for the number of salivary amylase genes – as a population, we are not uniform. Some of us have more amylase in our saliva than others.

Variation, of course, is only one part of the recipe for evolutionary change. In order to shift average characteristics of a population over time, natural selection needs to be acting on that variation. To test the hypothesis that natural selection is acting on human salivary amylase copy number variation, researchers have looked to see if human populations using a high starch diet have different copy numbers, on average, than  human populations using a diet low in starch.

The results are striking, and support the hypothesis that natural selection is acting on copy number variation in modern humans. In populations that have historically used a high starch diet, the average salivary amylase copy number is significantly higher than for populations that historically use a low starch diet. Detailed molecular analysis of the genomic region containing the amylase gene cluster in populations using a high-starch diet also showed signs of selection, in that they had greatly reduced variability (as one would expect if selection was acting). This reduced variability was not seen in these same populations for other genome regions with variable copy numbers. Taken together, these results support the hypothesis that natural selection is at work on the amylase gene cluster region in human populations. So, it seems that this story is still unfolding—and that we can observe a snapshot of the process at our moment in history.

Completing the circle: from man to dog

Two further lessons we can draw from this example require us to think back to the similar process that occurred during dog domestication. In dogs, there are numerous copies of pancreatic amylase genes, and dogs are currently variable for the number of copies they have. These duplication events in the dog lineage owe their selective advantage to the prior amylase duplication events in the human lineage. The human duplications were part of improving our reproductive success as we shifted over to a diet with greater starch content. While humans made the shift, dog populations associated with humans experienced a similar shift in environment—they, too, had access to greater amounts of starch.

This altered environment provided a selective advantage to variants within the dog population that, like their human companions, could benefit from increased starch consumption. The shift in the first species (humans) has a direct link to the shift in a second species (dog). This is an example of what is known as co-evolution: where two species in close contact act as major features of the other species’ environment, and selective changes in the one species shift what is advantageous for the other species. This human / dog amylase story is also an example of evolution “repeating” itself in two independent lineages—in this case, similar gene duplication events that boosted the amount of pancreatic amylase independently in dogs and humans. The technical term for this is convergent evolution—evolutionary paths that arrive independently at the same “solution” in two lineages.

While we will look at co-evolution and convergent evolution in more detail in later posts, it is worth noting these features now, while this example is fresh in our minds. The take-home message here is simple: evolution is not just a chance-based process, but also one that is, at least to a certain degree, repeatable. In part, this repeatability is based on organisms encountering similar environments, and these environments selecting for similar outcomes in both species. In the case of species in close contact, a shift in one species can open up a new opportunity for the second species.

In the next post in this series, we’ll examine further details of how genetic variation arises in populations, and how selection may or may not act on it.