I wasn’t suggesting I support the handwringing about putative declining genetic fitness. I was explaining what I think is going on with the folks who do support that POV.
The other point you and others have made is that human genetic change is slow; stupid slow. 10,000 years is an eye blink. If somebody is worried about myopia, get back to us in the year 21,300; that’s about 20K years after eyeglasses were invented. Then we can talk abut whether myopia has really proven to be a problem in the human gene pool. Until then, fuggedaboutit.
It’s a standard term for negative selection to remove deleterious mutations.
But it need not need to be all-or-nothing. It can be the case that a trait still has lower fitness is the current environment, but purifying selection is just weaker because the environment is less harsh.
In any event it’s also a question of the potential loss of a functional gene completely from the population. Suppose a loss-of-function (LOF) mutation arises; in a “less harsh” environment purifying selection is relaxed, allowing the LOF allele to increase in prevalence; then the LOF allele drifts to fixation by chance, and the functional allele is lost completely from the population. This may make it much more difficult for the population to adapt if the environment turns harsher and that gene becomes important again.
However, this is much more of a problem in a small population where genetic drift is rapid. This is why I’ve said: the concept of weakened purifying selection in a less harsh environment leading to loss of genetic “quality” is a real one; denying the validity of the very idea is not correct. Rather, it’s a quantitative question for population genetics as to of whether it’s important in the current human population. And the answer to the latter question is almost certainly no. That’s because:
(a) The size of the population is huge. Even if a LOF allele increases in frequency, genetic drift is inversely proportion to population size, so it’s highly unlikely that all copies of the functional allele would be lost completely from the population;
(b) The time during which the “less harsh” modern environment has prevailed is so short in evolutionary terms that little could have happened to “weaken” the genome overall, at worst a few loci may have slightly higher prevalence of LOF or other deleterious alleles.
So it’s extremely unlikely that any useful diversity has been lost, and if the environment were to turn “more harsh” again suddenly in the future, the population would be able to adapt quickly.
For reference, the notion of weaker or “relaxed” purifying selection is common, a few randomly selected papers:
Consider a loss-of-function (LOF) mutation, a mutation that yields either nothing or useless junk rather than a functional protein. A more precise statement would be: in some environments (where this protein is unimportant), there may be no impact on fitness. But in any environment where there is any difference in fitness, it will be deleterious, never beneficial.
This is almost always true with LOF mutations. Even though it’s better for an organism not to waste energy on producing things it does not need, it’s generally easy and quick to evolve lower levels of expression of a gene. So it’s better (from a genetic diversity persepecive, future capacity to adapt to changing environment) to have a functional gene temporarily downregulated to save energy rather than to lose the functional gene completely.
So this is why I said you cannot take the idea that all fitness is relative to environment too far. Many LOF mutations can have either no effect or a negative effect, but never a good one in any conceivable environment. That’s why the concept of “purifying” selection to remove them is valid.
ETA: I didn’t word some of that well. I did not mean to imply that selection can ever “anticipate” future environments (except in the sense of evolving plasticity).
More concisely: LOF is either neutral or deleterious, almost never good; and if a LOF allele goes to fixation in the population, diversity and capacity for future adaptation is lost.
I’m not sure I understand some positions. Experience shows us that really bad eyesight seems to be hereditary in some families - my experience is to know several families where a number of the parents and siblings sport the same coke-bottle-bottom glasses. (Poor vision can result in many hazards, even as simple as not being able to tell good food from bad) Type 1 Diabetes is apparently hereditary to some extent. Hemophilia is hereditary. This ignores a number of other deleterious genes that are becoming more prevalent due to lack of “winnowing”. (Again, not that I wish the “winnowing” on anyone). There are women who tend to have several miscarriages or premature births, or fail to conceive naturally and need IVF; the increased survival of people with genetic tendencies toward cancer; high blood pressure (yes, due to salt retention, but some people seem to be prone to it, others not, simply due to genetics); one family I knew had a history of liver problems which limited the mothers’ ability to carry children to term.
Another issue is the tendency to have children much later in life, which as I understand it means the children are more likely to have more damaged genetic material, whether it manifests immediately or simply adds to future problems.
Yes, as long as civilization can continue to deliver the tech required to compensate for physical shortcomings, this will never be a problem. The problem occurs when the support of civilization fails, even locally, for too long.
The other important question is of course - how fast are these genetic “problems” spreading in civilization? I tend to not believe the optimistic estimates of 20,000 years. When I took a course on science fiction and futurology in the 1970’s one guest lecturer, a biologist, suggested in 100 years a significant proportion of the population would have genetic issues, which I feel is too pessimistic. So let’s consider those the upper and lower bounds, and hope nothing disrupts civilization for us or our families during that time. Unfortunately, war, famine, earthquakes, ice storms, widespread power failures, etc. - all can and do occur and those caught in them may have problems.
But to get back to the OP - this is certainly an aspect of the question, that certain traits that were selected against for hunter-gatherer have been less and less selected for as civilization and technology progressed - even if it’s something as simple as the food surplus of agriculture supporting a class of artisans who don’t need keen distant vision.
But look back to the example of myopia that Broomstick and I discussed earlier. Type I diabetes looks almost certainly similar to this. Although Type-I is highly heritable (genetic susceptibility), the recent increase in incidence is attributable to environmental change, not to genetic change. There is no contradiction in this.
For example, to take one of the speculative but plausible hypotheses about Type I diabetes:
Type I may be attributable to a recent virus that triggers a dysfunctional autoimmune response, but much more so in people with a certain MHC haplotype (that’s part the genome that encodes the immune system). The increase in incidence is attributable to environmental change (the virus); but susceptibility is highly heritable (genetic), only people with one MHC haplotype are likely to get it. So it has a genetic basis, but not because the proportion of people with that less fit (“inferior”) genotype have increased in the population recently; in fact, that genotype only turns out to be inferior when the virus is around.
So, it’s both genetic and environmental. We could reduce the incidence either by changing the environment (getting rid of the virus), or by eugenics (if that were ethical) - selectively breeding out people with the susceptible genotype.
But the key is that while it’s genetic, it is not due to some “weakening” of the gene pool in the population; the genetics of the population is exactly the same as it was before the virus popped up. No evolution has occurred.
As H/Gs, our population never got higher than about 10M. So, yeah, if civilization disappeared, many of us would not survive. No one is arguing that all 7B of us could survive as H/Gs. That would be true even if we were all “perfect genetic specimens”. If you are postulating that we’d go extinct because of “bad genes”, then that’s just nonsense (outside of some catastrophic event that made the entire earth or most of it uninhabitable). BTW, this topic comes up every year or so on this MB. There have been many threads on this subject if you want to search. [This was in response to md2000]
[The correct term for “winnowing” is purifying selection.]
You will have to provide some evidence that any increase in prevalence of deleterious alleles has actually happened in any significant way, I’m not aware of any such evidence.
I have defended the principle that this can happen in the thread, but at the same time I think in practice it’s highly unlikely to be significant from basic population genetic principles.
As discussed, in the case of myopia and Type I it’s pretty clear that it has not happened. Although both are highly heritable, the recent increase in incidence was not due to a population genetic change, it was due to an environmental change. In the new environment it is true that we are now shielding the inferior genotypes (genotypes that are only inferior now in the new environment) from purifying selection with glasses and insulin injections; but the increase in incidence was not due to weaker purifying selection in the past, it was due to environmental change.
Again - growing up in an HG environment those people might not have had nearly as bad eyesight as they do in our environment. While being farsighted might benefit a hunter, being nearsighted might actually benefit the gathering portion of being HG. Of course, an extreme of either is bad, but Darwinian selection (DS, because I’m tired of typing the whole thing out all the time) doesn’t lead to perfect vision, it leads to vision that is good enough. A few, by chance, will have superior vision and a few exceptionally bad, but most will be good enough to get by.
To some extent - if it hits early enough in life the individual won’t be passing on any genes. It can also arise from injury or illness (anything that damages the pancreas can result in diabetes). In any case, no one is denying that the wrong alleles can lead to death prior to reproduction i.e. an individual that is not fit under DS criteria.
Yes, but carriers are unaffected so the allele continues to exist. Male offspring will die young, without modern medicine usually before they can reproduce but the female offspring do not undergo DS (at least not for that).
That concern has been brought up by other people in other places, and also applies to men with fertility problems as well. However, the portion of people conceived with IVF are such a small fraction of the overall population as a practical matter this has neglible effect on the species as a whole.
Er… very questionable.
For one thing, people who suffer cancer in childhood and survive treatment are frequently left sterile - they’ve already been selected again in DS terms even if they live to an otherwise healthy old age. If you have cancer after you have children are you not selected against under DS even if you die relatively young by today’s standards. If those same alleles that make you susceptible to cancer in, say, your 50’s actually increase the odds of you having more children then DS will select for those alleles.
And example of the last is Huntington’s Disease. It’s a devastating disorder than is invariably fatal, but people with the trait on average have more children than people without it. DS selects for Huntington’s (at least until it starts hitting victims young enough to impair fertility - one perversity of that disorder is that it strikes younger in each generation). It is modern civilization that enables us to select against it by identifying those with the allele that causes it so they can choose to not reproduce or, these days, even opt for pre-implantation screening to have kids without passing it on.
Of course, for much of human history salt was a rare and valuable commodity, so salt-retaining traits likely were selected for rather than against. There is also some speculation that the reason Americans of slave descent have higher rates of high blood pressure than the African populations they are derived from, and higher rates than those whose African ancestors came to North America voluntarily without being chained for weeks or even moths in a hellish belly of a wooden sailing ship is that traits allowing a higher likelihood of surviving the infamous Middle Passage lead to high blood pressure in our modern environment.
Type II diabetes is another interesting situation. The clearly is a hereditary factor at work and it causes much suffering in the modern world. However, it also confers benefits when food is scare, or in an environment with episodic famine. While such people are less fit in our civilization, if civilization collapses and we are forced to go back to subsistence agriculture or even a HG lifestyle (after a lot of people die off, of course) such people will be more fit than those who are not prone to Type II diabetes.
Yes, that would be a problem in any environment in human history.
Except… having children later in life is associated with living longer, and with the diseases/disorders of old age coming later in life. Having children later in life imposes a different type of selection pressure than having children early. Families that go many generations having children late in life are selecting for people who can do that and still have sufficient children survive to reproduce themselves.
The truth is we ALL carrying “bad” genes right now. Everyone has alleles that, combined with the right version of other genes, will result in Bad Things, or in the wrong environment will result in Bad Things. 1 in 25 people of European descent carry the allele that causes cystic fibrosis when they pair up with another carrier. That means you’ve met a LOT of people in your life who are carriers, you might even be one yourself and never know it. Rinse and repeat with various traits for every ethnicity on the planet.
And, ironically, someone with a “problem” gene leading to Type II diabetes in our civilization might survive better than average if something “disrupts” civilization and food becomes scarce for awhile.
Which is why I don’t think we should do a lot of tampering with the human genome at this point - the issues are more complicated than they initially appear to be, and we really don’t understand all the details.
I’m not disputing you, but is there a theory about why Huntington’s carriers have more children? Is it biological or social? etc. Wiki was uninformative that I could see. Any links would be appreciated.
It may be that those with HD are slightly less inhibited than their peers long before the more serious symptoms of the problem manifest. It may be that a side effect of HD is increased libido. Those seem to be the two leading hypotheses.
It’s not a huge difference in reproductive rates, but it is one that show up when studying these families over time. Those with HD have slightly more children than their siblings without HD
If a loss-of-function mutation undergoes positive selection because it’s advantageous to lose it in the modern environment, that’s adaptive natural selection, not a weakening of purifying selection. I’m not trying to make a “no true Scotsman” argument - it’s a quantitative question, and this is rare; so it’s not a counterargument to the idea that a weakening of purifying selection increases the frequency of deleterious alleles. It is a basic tenet of population genetics that most mutations are neutral; and that among those with any effect, most are deleterious.
You’re describing a benefit to one particular organism. Evolution happens to populations. And from a population genetic perspective, it’s what happens to the population of the genes carried inside the organisms that matters.
If purifying selection is weakened, that means the survival of more defective genes (alleles) into the next generation. Of course, by definition, that’s a benefit to those defective copies of the genes - they get to live on!
This has been repeatedly questioned in this thread; but the concept of purifying selection (“winnowing”, if you like) is really not controversial, it is standard populations genetics.
Most mutations are neutral (have no effect of fitness); of those that have any effect, most are deleterious (loss of function or reduced function); beneficial mutations are rare.
Purifying selection is negative natural selection to remove deleterious mutations (as opposed to positive selection for beneficial mutations). Now consider a variable environment. At a given locus, purifying selection may be stronger or weaker, depending how “important” the trait is in the prevailing environment. If individuals bearing a deleterious mutation for the trait are very likely to die without offspring, this is strong purifying selection, under which deleterious mutations at a locus for that trait are removed quickly from the population. If the environment changes such that the trait is less critical to survival, purifying selection is weaker or “relaxed”. Furthermore, if the environment changes such that the trait is no longer important at all, then there is no purifying selection acting at all at that locus: in fact, we should now re-categorize mutations at that locus in the current environment as “neutral” rather than “deleterious”.
It is mistaken to claim that “genetic quality” is a meaningless term as some have done. Genetic load is a valid concept in population genetics, loosely the “baggage” of deleterious mutations carried in a population. In population genetic terms, there is even a meaningful concept of a “perfect” genotype, the optimal theoretical genotype in a population. It is certainly true that fitness is always measured relative to the environmental context, but we should not take this relativism too far, to a point of insisting that there is no such thing as a “defective” gene.
Now, considerations of genetic drift are critical. Drift is the random variation of allele frequency in a population. It is faster in small populations: if you flip 1000 coins, they will always be around half heads; if you flip 10 coins, the proportion of heads has much higher variance. If there are two prevalent copies of a gene, a functional allele and a defective allele, the probability that one of the two alleles may be completely lost is much higher in a small population.
Putting these ideas together: weakened purifying selection is much less likely to be a problem in a large population. If deleterious alleles are removed more slowly, that’s unlikely to be catastrophic in a large population, because there are still plenty of functional copies of the gene around. It is highly unlikely in a large population that all functional copies of a gene will be lost by genetic drift, and there is plenty of time available for slower purifying selection to act.
Thus, with the huge human population, and the short time for which a “softer” environment has prevailed, it is highly implausible that any proposed broad “genetic weakening” of the population has occurred. This does not, in principle, exclude the possibility that there may have been significant effect at a few specific loci. But the burden is upon those who claim “genetic weakness” to demonstrate that there has been a population genetic change over time. It is not sufficient to demonstrate the heritability of the trait. Many diseases with high modern incidence may have a strong genetic basis (heritability) in the modern environment, but that in itself shows nothing. In most cases, the higher incidence of disease is probably attributable to environmental change, and the heritability is only observed in the new environment. So, it is both genetic and environmental, but the increase in incidence is not attributable to population genetic change (“lack of winnowing”), it is attributable to environmental change.
But populations are composed of organisms, and the organisms living on isn’t just beneficial to the defective genes; it’s beneficial to all of the other genes (most of them not defective) that happen to be occupying the same organism.
At different levels this is indeed where the disconnect between the perspectives is and how this ties back to the op.
Let’s ignore the possibility suggested by Chronos that a LOF mutation can in fact be advantageous, Riemann’s point is basically saying the above: sure loss of this particular function might be neutral now but the future may be different. It may suddenly be harsher.
It does tie back. Nevermind that human evolution actually occurs faster than some here seem to think it does. Again, there have been significant changes just since transitioning from HG to farming and skin color has changed in populations very rapidly. The point is that humans by way of becoming the meta-organism of human society with accumulated knowledge and technology resultant of written language as a tool adapts to changing matches of our selves and our environments by means other than evolution. We create tools and we change our environment.
Our environment will change. It is on track to become significantly harsher with flooding of coastlines, greater weather volatility, and mean temperature increases. Who knows whether or not we will someday colonize environments much harsher yet. But our adaptations to these possibly dramatically changing environments will be at the meta-organism level and acting upon the selection of ideas. Farming, writing, etc. did not spread not primarily by selection of the genes associated the ability to do those things but by the spread of the concept and the ability to build upon successive levels of concepts. We adapted to cold and to hot locales with technology and ideas before any genetic changes occurred.
The essential trick of humanity was to adapt to environments that would be too harsh for any individual’s genetic make-up by way of human intellect exceeding the individual (as chronos put it). We are extremely successful generalists by way of group intellect not primarily by way of gene diversity.
Is that change, humans adapting by way of culture and technology, suddenly going to disappear? Or is it more probable that we will develop more technology to further deal further changes in both our environments and ourselves? Because its disappearing is what a return to a “more harsh” environment in this context means.
Genes that predispose to myopia, for example, are to the best of my knowledge, not significantly decreasing reproductive success in the current environment and it is improbable that they will in any non-apocalyptic future case. It is much more likely that they will have less impact on reproductive success in the future than they have now. They therefore are not negative or “weak” traits from a fitness perspective now or in a probable future.
And if there is an apocalypse (nuclear, zombie, asteroid, whatevs)? We remain social creatures and in the rubble quickly rebuild groups in which our potential strengths and weaknesses form into teams that are greater than the parts competing against other such teams with our success more dependent on the ability of the team to work together to outcompete the other teams than on our individual genes. Within our own teams some traits will have more reproductive success than others … and so it goes. Purifying selection.
I appreciate the education that it is a standard phrase that I was unaware of. And it is a tautologic one, to the point of triviality. If something is selected against it is being purified and is deleterious by definition. If not it isn’t. How much impact does a gene have, net, on passing copies of itself into future generations? Strong negative? Then it is selected against. Strong positive? Selected for. And all points in between. Yes, there can be weak positive and weak negative selection pressures.
Returning to our illustration case, is there any selection pressure, strong or weak, for or against a predisposition to myopia in the modern environment of humans? If there is none in either direction then it is by definition neutral. To any degree that technology and culture have made genes that previously were deleterious to being of no impact on the magnitude to which those genes occur in future generations, technology and culture and made those genes no longer deleterious and thus not subject to “purifying selection”.
I love Broomstick’s example of Huntington Disease (HD). To the degree that the gene has increased its incidence over time because it hits after peak reproductive years and something about it leads to greater reproductive success during those years it is NOT a deleterious gene from a fitness perspective. It’s net was more copies of the gene. Once people with the gene choose to not reproduce, or abort affected fetuses, then it becomes deleterious. HD is the subject of purifying selection now by virtue of its being the subject of purifying selection now but while it was not it was not and therefore from an evolutionary perspective was not “deleterious.”
I like this phrase from the article: “antagonistic pleiotropy” - genes that may have beneficial impact during reproductive years along with unselected deleterious effects with increased age. What is the net impact of the gene on the gene’s presence in future generations? That is what defines its fitness.
But this is not how evolution works. Most populations are not constrained by birth rate. It is not survival that matters, but relative chances of survival. If this particular organism died, another would survive in its stead and pass its genes into the next generation instead. Sexual recombination and chromosome assortment means that all other genes are shuffled around randomly, so there is no expectation that the rest of the genes would be on average any better or worse between this organism and another organism that survived in its stead. So all that matters from an evolutionary perspective is the particular locus under consideration: is the defective allele subject to purifying selection or not?
Everyone surviving is “good” for the organisms, of course, because we like being alive; but it’s “bad” for evolution. Purifying selection requires death with fewer offspring.
Note that, in humans at least, genes that have no effect until after reproductive years are past are not entirely neutral. A wise elder can still contribute to the success of his or her descendants or other relatives.
Natural selection is indeed a tautology: that which is better at surviving tends to survive. But the fact that the definition of something is a tautology does not mean that the consequences are trivial. For example, the non-trivial importance of natural selection is that it explains apparent design, and it took humanity a long time to figure that one out.
By the same token, you should not be so dismissive of the concept of purifying selection. The definition may be tautologous, but the ensuing population genetic processes are far from trivial. Populations with high genetic load can can very much go extinct under certain circumstances. The accumulation of deleterious mutations is a genuine problem for evolution, with several interesting and non-trivial evolutionary resolutions. Indeed, it’s one of the explanations for sex, which is extremely messy and has many drawbacks, hardly a trivial consequence!
This is why the genetics of ants is so interesting. The vast majority of ants don’t reproduce at all as individuals, they work tirelessly to get identical copies of their genes that are in a different body into the next generation.