At the Guardian Hay Festival in Wales, I was asked a question that almost always comes up when I speak in public: Is natural selection/evolution still operating in humans? From first principles we almost have to say “yes,” for if humans experience differential pre-reproductive mortality, or differences in reproductive output (which is true), and if some of those differences are affected by genes (as they almost certainly are), then selection will be operating. But first principles are not enough: people want hard evidence for natural selection in our species.
The classic example of selection operating on humans—selection that’s certainly going on today—is that occurring in sickle-cell anemia, where a mutation in the beta chain of hemoglobin confers (in single dose) some protection against falciparum malaria. Individuals with one copy of the mutant gene have protection, but individuals with two copies have sickle-cell disease, which is invariably fatal. This kind of selection keeps the mutant gene present in appreciable frequencies in African populations.
A while back I cited a study suggesting that selection is operating on cholesterol, blood pressure, age at first reproduction, and other traits in modern humans. A new study in PNAS by Cynthia Beall and 27 colleagues (reference below) gives evidence for selection in humans on another hemoglobin-related trait: adaptation to high altitude.
The reason this study has so many authors is because it’s really three independent (but related) studies agglomerated into one publication. All the studies examine the region of the genome that contains the gene EPAS1, which encodes half of a transcription factor (a protein that regulates the expression of other genes). Among its functions, the transcription factor helps control the production of red blood cells, increasing their number under low oxygen conditions (hypoxia). This is a short-term adaptive response to living at high altitudes, but can also cause excessive production of red blood cells, leading to chronic mountain sickness that can kill people or reduce their reproduction. Some mutations in EPAS1 that increase its expression, for instance, are associated with increased hypertension and stroke at low altitude, symptoms similar to that of mountain sickness.
These facts suggest that people living permanently at high altitudes might undergo selection at EPAS1 to reduce the fitness consequences of excessive red blood-cell production. The three studies suggest that this is indeed the case:
- Genome-wide comparisons of high-altitude Chinese (Tibetan) populations with related but low-altitude Han Chinese populations show 8 DNA regions that are highly differentiated between them. All eight are in the EPAS1 region. This suggests (but of course does not prove) natural selection differentiating this region between the populations.
- An association study showed a relationship between EPAS1 sequence and hemoglobin concentration in Chinese Tibetans. In all cases, the DNA sequences in higher frequency were associated with lower hemoglobin titer.
- This association study was replicated in another sample of Chinese Tibetans, with similar results: individuals having the DNA variants in highest frequency showed the lowest hemoglobin concentration.
These are suggestive results, made stronger because differentiation in this region was predicted from knowing the function of the DNA. But the results are not conclusive. EPAS1 helps regulate at least a hundred genes, and perhaps selection is acting not on hemoglobin concentration, but something else. Indeed, an earlier study of Andean populations compared to lowland ones showed no sign of selection at EPAS1. (Perhaps there is a specific Tibetan mutation for resistance to mountain sickness that is not present in the Andes.) A more conclusive result would be to follow individuals of known genetic constitution at EPAS1 throughout their life, seeing if differential survival or reproduction is associated with specific mutations at that gene.
If the results do stand up (and I find them fairly convincing), we’d have a nice demonstration of selection acting in our species over a short period of time. Despite our technological and medical advances, we are not immune to Darwinian natural selection so long as people continue to die before they stop reproducing, or have different numbers of offspring, and so long as this differential mortality/reproduction is associated with genetic differences between individuals. It will be a long time, if ever, before we free ourselves from the kind of selection that acts on all other species.
________
Beall, C. M. et al. 2010. Natural selection in EPAS1 (HIF2α) associated with low hemoglobin concentration in Tibetan highlanders. Proc. Nat. Acad. Sci. USA 107:11459-11464
At the risk of people accusing me of being a troll or thread-jacker, I’ll move my comments on human intelligence interrupting evolution here.
See, while this is interesting, it also allows me to clarify my point, which was that intelligence and tool-making ALLOW humans to interrupt evolution by choosing what impacts them. Let’s look at the impacts of the EPAS1 gene:
“but can also cause excessive production of red blood cells, leading to chronic mountain sickness that can kill people or reduce their reproduction. Some mutations in EPAS1 that increase its expression, for instance, are associated with increased hypertension and stroke at low altitude, symptoms similar to that of mountain sickness.”
But if you look at the effects, particularly hypertenson and stroke, those can, in fact, be treated with drugs. So someone that has those additional side effects might be able to live perfectly well and reproduce perfectly well simply by taking drugs to reduce hypertension, and other things to reduce the risk of stroke. If there are enough of these, there wouldn’t be ANY significant statistical difference caused by those extra factors; people with the hypertension and stroke risks from the EPAS1 gene expression simply wouldn’t die or reproduce statistically significantly less than those that didn’t have the gene or the added risks from it. Thus, those selective factors end up going away, because we filter them out and correct for them.
The same thing can be said for the differences in high and low altitude. It is, in fact, theoretically possible for us to invent a drug that someone can take to increase red blood cell production when at high altitudes and reduce it at low altitudes (it might not be the same drug). So, then, people who don’t naturally have increased red blood cell production can simply take the drug and in fact have that — temporarily, while in the environment that needs it. And those who have the increased production, when coming down to lower altitudes, can take the drug to reduce it. Thus, as long as the drug is readily available and has no other significant side effects (which rarely happens), there’s no difference selectively between those who have the EPAS1 gene and those who don’t. Or, rather, there ARE differences, but no selective factor can select on them since humans control for it.
Now, you’re correct that practically selection will work on us for quite some time because we don’t correct for everything and can’t correct for extremely drastic changes that we aren’t ready for. So, as I said elsewhere, the big things and the little things will always count. But we interrupt evolution in a signficant sense using our intelligence and our tools, and I just want to make sure that that is properly recognized.
You’ve got your own blog, so could you post these long comments over there? I’m not going to point out your many misconceptions, including the fact that mountain sickness can be successfully treated at high altitude, or that drugs are always completely successful at reducing hyptertension.
That is not a nice reply; I mean, to a man with so many degrees? Surely, there must be a few words that are perfectly true.
“You’ve got your own blog, so could you post these long comments over there?”
He is a troll. His goal of causing aggravation to readers of a different blog will not be met if he posts on his own blog.
“If wishes were fishes, we’d all cast nets.”
— Frank Herbert (Dune)
mor power to you oldbob. long live the dune
What about the enzyme lactase and the elimination of primary lactose intolerance in humans as an example of present day evolution in our species ?
It is a quite recent mutation on chromosome 2 which allows the production of lactase to continue after childhood – and this provides the bearers of that mutation the possibility to drink cow’s milk and use dairy products. That must provide at least some advantage in those areas where cow’s milk is available?
Yes, I wrote about this in WEIT and also posted on it here in March.
Another example is amylase in saliva, in populations with a historically cereal dominated diet.
Most interesting! Since we seem to be touching on other examples, there’s a big enigma out there in the mitochondrial aldehyde dehydrogenase (ALDH2), an enzyme which has been touched on in comments here before.
ALDH2 is the enzyme that is believed responsible for most of the conversion of ethanol-derived acetaldehyde to acetate. It is also the enzyme in which the mutation is found in Asians who are intolerant to (display facial flushing in response to) alcohol- the mutation results in a Glu–>Lys substitution at position 487, which has an allosteric effect on the tetrameric enzyme such that heterozygotes for the mutation still have extremely low ALDH2 activity. With equal production of ALDH2a and ALDH2b* subunits, only something like 6% of all tetramers will be all ALDH2a subunits; the level of activity is consistent with 6% of normal.
Now, here’s the evolutionary aspect, or maybe better put, the evolutionary enigma. The enzyme clears acetaldehyde, but there is no clear indication of what the physiological substrate actually is. It works on a wide variety of aldehyde substrates so it is thought of as a general-purpose aldehyde-oxidizing enzyme, handling any dietary aldehyde that comes along. Orthologous forms are found in other species, so it’s not something that has arisen just so we can drink microbrews (and wine if you insist), but even those Asians who are homozygous seem to have no problems as a result of having inactive ALDH2. This would seem to make it a superfluous enzyme – perhaps the only one in that category(?)
But why, then, has the mutation been assimilated in Asians? Something like 50% of any such population display the flushing reaction, most of whom are heterozygotes. The situation seems somewhat reminiscent of the sickle-cell situation, but without any underlying cogent explanations.
*I think this is the accepted terminology for the subunits but I’m not positive. Also, some acetaldehyde is doubtlessly cleared by the (paralogous) liver cytosolic ALDH1 enzyme. Further, there are something like 18 distinct families in the ALDH superfamily across all phyla, of which we have something like 12, most of which act on distinct aldehyde substrates involved in intermediary metabolism.
“A while back I cited a study suggesting that selection is operating on cholesterol, blood pressure, age at first reproduction, and other traits in modern humans.”
Your link here goes to the same NIH sickle cell link as the one above it. Is that what you meant?
So, I’m a little confused about the caveat.
In one geographically distinct population living at high altitude, we see a distinct mutational pattern leading to a beneficial adaptation. And in another geographically distinct population, we don’t see that mutation.
So, this is evidence against natural selection, how? Seems to me it’s exactly what you would predict under the circumstances. And by inference, you should find some other heme-regulatory gene in the Andean population that confers the same advantage (or not, and they suffer higher relative rates of altitude sicknesses).
Else, you could easily run into an inference of “god-directed” mutational patterns if the same mutations in the same transcription factor showed up in geographically separated populations.
Or am I being hopelessly simplistic?
It is NOT evidence against natural selection. It just shows that the opportunity (alternative allele) must also be there.
Layman’s answer until Jerry or another biologist can weigh in: It’s not strong evidence against, but if the scenario is as you describe it, we have to assume that either the proteins being coded for are not particularly likely to mutate into a more high altitude-friendly form, or that there were different selective pressures, or maybe that the Andeans just got unlucky.
To put it another way… we’d like to believe that the EPAS1 gene has a large number of mutational pathways that would allow it to improve fitness for high altitude populations, that these mutations show up fairly regularly, and that therefore anywhere they are selected for, we’ll see them. The reason we’d like to believe that is then we don’t have to do any special pleading about the Tibetan Chinese. Ideally, we say “all populations experience EPAS1 mutations that improve high altitude fitness, but those mutations are only selected for in high altitude areas”. The Andean data may force us into a somewhat-less-desirable though still plausible fallback position of “occasionally some populations experience EPAS1 mutations that improve high altitude fitness, and the Tibetan Chinese had the good fortune of being one of those populations and living in conditions that would select for those mutations.”
Does that make any sense?
That would be my understanding of the issue. But I still don’t understand why the absence of EPAS1 mutations in non-Tibetans warrant the caveat as being inconclusive, as Dr. Coyne suggests.
Unless there’s no other pathway to achieve the adaptation other than EPAS1 gene products. In other words, without the product of the mutations in that particular gene and no other gene, high-altitude adaptation doesn’t occur?
But I still would predict that in some populations living at high altitudes, you would see a different level of penetrance of the mutations. Some populations (Tibetans), see a lot; some (Andeans), little or no.
To me, it would seem to be quite improbable that in geographically diverse people, the same mutation or sets of mutations would show up conferring the same advantage. Unless that’s a biological bottleneck at that specific gene required for improved high-altitude fitness.
After all, only Africans and their (close) descendants have the sickle cell trait. Other populations where malaria is endemic do not have it. Yet, we cite sickle cell trait as evidence FOR natural selection. Precisely BECAUSE it’s population specific.
This seems to be telling the same story.
I’m just quibbling; perhaps wanting this to be more of a slam dunk than an easy lay-up. In any event, it certainly doesn’t seem to be a three-pointer from the baseline.
That is a good point, actually. See my comment below.
Well see, mutations happen at random. Beneficial mutations are selected for, but there is no reason to think that the same mutations will happen in two different populations under similar circusmtances. While the resulting phenotypes may be similar (“convergent evolution”), underlying modifications are typically different.
Sorry, but this is as elemental population genetics as it gets.
Eh, but these studies were not looking for a specific mutation (though it’s conceivable that’s what they detected), they were looking for evidence of selection going on in the EPAS1 region.
So I think your answer is only partial. If it really is just one specific mutation in the Tibetan Chinese population, then fine, sure. But it could also be that there are any number of potential EPAS1 mutations that would modify gene expression in such a way as to potentially be more fit for high altitudes. The latter seems especially plausible given that there were multiple (8) areas within EPAS1 that showed evidence of selection. It’s not a deal-breaker to have to rely on one or two unique mutations in the Tibetan Chinese genome, but I think it makes it less of a slam dunk.
IANABiologist, so maybe I got all this wrong. But that was how I interpreted the post.
OK. First, my response was to Kevin, not you. So, I am sorry if the response came across the wrong way.
Second, there are different ways of responding to low oxygen concentrations that are chronic. While tunning the structure of hemoglobin is one, increasing the capacity of lungs is another. And that is something you see in the natives of the Andes.
The president of Bolivia who is a native participated in a soccer match some years ago, just to show how safe it is at La Paz, one of the highest-altitude cities in the world. Except that if it is safe for him it doesn’t mean it would be safe for your and me, since our ancestors haven’t been living there for hundreds of years.
No worries. After re-reading all the comments in this nested thread, I think we are all pretty much on the same wavelength 🙂
Question: Is the fact that there were 8 regions in EPAS1 showing selection indicative of multiple truly independent mutations in EPAS1? Or is it just as likely that one successively built off the last, e.g. there is no selective advantage to mutation Y, unless you also have mutation X?
Or, am I totally misinterpreting the implications of their being “8 regions” that show signs of selection?
The reason I ask is that if the 8 regions of selection is indicative of 8 truly independent EPAS1 mutations, then I would still maintain that it’s a little troubling that nothing EPAS1-related showed up in the Andean population. If, on the other hand, it’s just as likely that it was a serial series of mutations enabled by the last, or if I am misunderstanding and this really refers to a single mutation, then of course the lack of the same mutation/series of mutations in the Andean genome is entirely expected.
The caveat came because this observation itself is not all that “dispositive” (as the lawyers say). You can get this pattern of differentiation simply by a sampling event occurring during population foundation. Or, if another gene, linked to the EPAS1 locus (that is, close to it on the DNA strand), was the real target of selection, and the EPAS1 allele was dragged along for the ride (this is called “hitchhiking” by population geneticists). The case is stronger with the association study measuring hemoglobin concentration, but that’s two observations and not just one.
OK. Yes. I understand.
Thanks for clarifying.
To me, the really interesting (and probably unanswerable) questions is not so much whether selection is taking place — both first principles and evidence like this suggest it is — but rather:
a) Are we still firmly in the midst of the sudden ballooning of cranial size and cognition that started ~200k years ago, or have we reached a point where increased cognition is no longer a significant selective advantage? (i.e. assuming no species-ending catastrophes will evolution produce hyper-intelligent humans in another few dozen millenia?)
b) Has technology caused an abrupt shift in the types of selective pressures being exerted on human evolution? Or is it still more or less the same old game? (I imagine technology is way too recent for this to even manifest itself yet)
c) Assuming civilization more or less as we know it continues indefinitely — which is a pretty huge assumption, but run with me here for a second — will it ultimately prevent speciation? I imagine the answer is yes, simply because the mobility afforded civilization as we know it effectively bars allopatric speciation (unless someday we finally manage to form colonies off this rock, of course), and it is seems like culture would effectively prevent any of the other types of speciation.
(I suspect the last is a moot point because civilization as we know it, even if we were able to find a way to dodge looming environment problems, is probably just not sustainable on the timescale we are talking about. It seems neither pessimistic nor controversial to assert that civilization will most certainly either implode, flame out, or radically transform at some point in the next several hundred thousand years, so…..)
Like I say, I think all of these questions are unanswerable, at least for the next several life times. (a) might be answerable in a few thousand years. (b) and (c) are probably unanswerable, and quite possibly moot, since I am audaciously asking about what will happen if the next hundred thousand years or more turn out to be materially similar to the previous couple hundred. Probably a dumb question, but I can’t help but wonder at it anyway.
Referring to your point b):
It depends on your definition of technology. If the definition includes the use of fire for cooking, farming, fishing, etc. then it may not be too recent to see changes.
point c): we already have human speciation – Republicans and humans 😉
Excellent point about (b), especially given the fairly prevalent theory that cooking enabled our jaws to flatten out (is that still the orthodoxy?) I was more referring to post industrial revolution technology, but I certainly didn’t specify that.
Oh, and I forgot:
a.2) If the selective pressure for larger craniums has leveled off somewhat, does that mean the cervix will finally start catching up, and in a bunch more millenia Homo sapiens can stop having such difficult births?
Heh. At the risk of stating the obvious, the presence of creationists and Republicans seems to indicate that increased cognitive capacity and function is not required to be preferentially successful at procreation.
Yes, interesting questions. I see in your later comments I started out with the same simplistic and erroneous version of “evolution” and “human non-evolution” as you. This is of course a background that makes them extra fascinating.
As for the questions:
a)
I’ve seen some back and forth on that one since it is really iffy to test a fit to the data. So I’m fairly certain there is no such evidence. 😀 What seems clear however is that cranial size has gone down appreciably in modern sapiens compared to older and neanderthals (~ 100 ky).
Here is the latest I read on this.
The less resolved figure doesn’t allow to see the claim or counterclaim above, but instead shows the backdrop of the hominin steady cranial capacity (ie brain size) over the last 3 My.
The hominin increase in turn is immersed in a primate brain size increase that goes back at least 4-5 My. The article goes into theories on why all of this is.
b)
Depends on how you define technology. More importantly, culture is a main driver according to gene-culture evolution, which WEIT has discussed before. IIRC that linked me to this article.
c)
Not according to HG Wells: it will cause it (“The Time Machine”)! :-~
Quite plausible if and when we start to migrate through the solar system through the Oort cloud resources of minerals and volatiles to the next solar system and so forth. (On a log scale, appropriate to measure exponentially increasing economical and technological capacity, it is really the Moon that is the large step here. And we made that one already!)
Nothing prevent speciation as we disperse; not that there will be any means to check it or anyone who would care.
Again, depends on how you define civilization. Culture has certainly been a sustained trait on such time scales (see the last link above).
Oops, local link for the gene-culture review. Try this instead.
Interesting that people would ask if evolution is still going on in humans. Given that we have been evolving over the past millions of years, why would one think that we might stop? Do they believe we have reach perfection or perhaps, our environment has become so stable that no more change is needed?
The argument I always here is that technology allows “the weak” to reproduce just as effectively as “the strong”, so we have short-circuited natural selection.
Which sounded vaguely plausible to me before I actually started learning anything about evolution beyond what they teach in high school…
High rates of travel and the ability of the gene pool to go from one end of the planet to another in a matter of hours would seem to argue not against ongoing evolution (which is happening regardless of what we think about it), but of the low likelihood of a speciation event where homo sapiens sapiens branches off into two separate groups.
Eg, Homo sapiens sapiens and homo sapiens not-so-sapiens, just to bring the discussion back around to my earlier comments regarding creationists and Republicans. Like cave salamanders, only with brain capacity and reasoning power substituting for eyesight.
Are there studies comparing the evidence/amount of recent natural selection on humans (specially those living on not-so-harsh conditions) versus other animals?
With reference to the topic of humankind ceaselessly evolving, and our brains ceaselessly being modified by natural selection and becoming adapted to changing cultural as well as physical environmental circumstances, it is interesting to read what Charles Darwin was thinking on this. Darwin suggests the possibility of religious indoctrination having permanent (inherited) effects on the brain: “Nor must we overlook the probability of the constant inculcation in a belief in God on the minds of children producing so strong and perhaps an inherited effect on their brains not yet fully developed, that it would be as difficult for them to throw off their belief in God, as for a monkey to throw off its instinctive fear and hatred of a snake.” Charles Darwin, Autobiography, p. 93.