created by jsamke on 29/11/2024 at 09:20 UTC
462 upvotes, 24 top-level comments (showing 24)
I understand that symptoms of such diseases may only show up after the people have already reproduced, so there might be not enough evolutionary pressure on the single individual. But I thought that humans also owe a lot of their early success to the cooperation in small groups/family structures, and this then yielded to adaptations like grandparents living longer to care for grandkids etc.
So if you have a group of hunter-gatherers where some family have eg huntingtons, or even some small village of farmers, shouldn’t they be at a huge disadvantage? And continuously so for all generations? How did such diseases survive still?
Comment by arrgobon32 at 29/11/2024 at 14:26 UTC
696 upvotes, 4 direct replies
While it is true that diseases like Huntington’s primarily passed down through inheritance, a not insignificant number of cases arise spontaneously through random mutations.
The disease can definitely “die out” in a family/community, but it’s only a matter of time before it appears in another population.
Comment by limminal at 29/11/2024 at 17:06 UTC
118 upvotes, 3 direct replies
Hello! I am one of the people in the HD field who calculated the *new mutation rate* for the expanded HTT CAG repeat, so a question I can help answer! New mutations maintain the HD mutation in the population.
There is a constant churn of new mutations for HD into the population because they expand from non-pathogenic premutation alleles called *intermediate alleles* (27-35 CAG) into disease causing alleles (>35 CAG) between generations. There are more intermediate alleles in the population than HD alleles, so intermediate alleles act like a reservoir.
Also, new mutations for HD typically occur with presentation later in life, so people are unaware they have the new mutation until well after they have had children.
Nearly all genetic diseases have their own way of maintaining frequency in the population. This just happens to be how it occurs in HD.
Comment by RudeHero at 29/11/2024 at 17:52 UTC
26 upvotes, 0 direct replies
What others are saying is generally true. I'd like to add one more to the pile.
According to a college human behavioral biology class i watched on YouTube, there's a running theory related to the prodromal (earliest) phase of the disease.
The earliest symptoms are often personality changes- unpredictability, irritability, risk taking, and so on. People don't realize it's a symptom of a disease at first- they think their partner/parent/whoever has had some kind of dramatic, uncharacteristic mid life crisis and become a jerk.
Basically, within those first few years the sufferer is more likely to run off and have unwise sex with new partners. Especially for men in a certain age range, this can significantly increase the number of times their genes are passed on
Comment by MyAcheyBreakyBack at 29/11/2024 at 14:37 UTC
149 upvotes, 2 direct replies
Natural selection doesn't care a bit what makes you live the longest. It only cares what makes you reproduce the best. A disease that only tends to arise after you've reproduced and your offspring is old enough to care for themselves is not going to stop itself from being passed on.
Comment by hippocampus237 at 29/11/2024 at 15:04 UTC
24 upvotes, 1 direct replies
We all have the Huntington’s gene which has the CAG repeat. Repeats can be in normal range and then expand past the point of pathogenic in subsequent generation.
The repeat expands as the DNA replication machinery makes errors that are not corrected- common in repetitive sequences.
The age of onset is often past the time that someone has had children as well.
Comment by Mitochondria95 at 29/11/2024 at 16:26 UTC
11 upvotes, 1 direct replies
Howdy I’m a geneticist so perhaps I can offer some insight. Selection of a trait can be negative (bad, so get rid of it), positive (good, keep it), or neutral (also called drift which means it’s down to probability). A trait like Huntington arises from a spontaneous mutation and can be inherited. If it kills you after reproductive age, it can still be a negative trait but has relatively weaker negative selection. You are right that selective pressures go beyond simple reproductive milestones and there is evidence that human traits favor ultra post-reproductive qualities (eg menopause). But evolution is NOT an infinite numbers game and life is a bit more complicated than mathematical models of selection. To this end, we see all sorts of genetic diseases arise in humans and non-human species which tells us, bare minimum, that selection is not a perfect engine. Take BRCA1/2 mutations — why are these so common?! Well we know why.
The classic ”Huntington’s disease” (HD) arises in two ways. (1) Sporadically from mutations (10% of cases or so). Not much we can do about that. And (2) inheritance. The inherited one we can surely do something about? Historically, we find HD arises in small towns and can usually be traced to a family lineage or sometimes one specific individual! This is called the founder effect and underlies why some groups develop high rates of genetic disease (eg religious enclaves where people marry within a small group like Orthodox Judaism). If a founder has a sporadic case of HD and then goes on to be the ancestor of a whole town, then selection has little to work with. Evolution, again, is not an infinite numbers game. Sometimes mate choices are limited and that is the limited playing field for selection to act on. What are humans to do? Not reproduce out of solidarity?
Take in mind, HD is only well described in modern times. We do not know how many groups of hominins over the last, oh, 2 million years were wiped out by HD. The locus where HD happens is conserved which is a genetics term that shows the area has undergone a lot of purifying selection.
In modern times, one can stop HD if it runs in their family. A little IVF and voilà.
Comment by ThePhilV at 29/11/2024 at 15:14 UTC*
10 upvotes, 1 direct replies
You're coming at this from the viewpoint that humans are done evolving. We aren't. There are a lot of traits that are in the process of evolving out of our gene pool, but we aren't there yet, and might never be (like wisdom teeth, tailbones, pinkie toes, etc.)
There's also the question of "does this hinder procreation"? If not, it probably won't won't evolve out of the gene pool at all. Evolution isn't like writing different drafts of an essay, where it's "trying" to make every last aspect of the "final" product as perfect as possible. We're a tangled mess of glitches that don't cause enough harm to kill us before we mate, things that work well enough, and leftover bits and pieces that we don't really need any more but there's no reason to get rid of them. Bodies are junk drawers - useful but messy. You're viewing the process as a series of conscious decisions, but that's not what evolution is. It's a haphazard "this doesn't not work" scenario.
As for your group of farmers scenario, it sounds a little bit like you might be suggesting eugenics? Which is a largely failed "science" that aimed to improve the human gene pool through selective breeding, basically. But it's largely impossible, and leads to a LOT of problematic behaviour (like the holocaust), and ignores the possibility of things like recessive genes, reduced genetic diversity (leading to more problems), etc.
Comment by Unironically_grunge at 29/11/2024 at 14:47 UTC
4 upvotes, 0 direct replies
They would be at a disadvantage. Generally speaking the more members who are affected with the symptoms, the bigger the disadvantage. (Just it's a disadvantage in terms of life quality and not reproduction speed or rate).
There's a tiny bit of luck with genetics. So there's maybe 3 different states (next gen is better, the same, or worse) that can come from 1 state. Some hunter-gatherers who maybe had several successive bad states in a row probably died out, but others who had a few better next gens by luck were able to continue to survive.
The diseases survived because on average, they didn't affect human beings that badly that it stopped them from preproducing. Even if they were at a disadvantage the disadvantage didn't affect their quality of life badly enough to alter their reproduction patterns.
Comment by jtoomim at 30/11/2024 at 00:36 UTC
5 upvotes, 0 direct replies
The issue with Huntington's is that there's a small segment of DNA that's unstable and prone to errors during DNA replication. In particular, there's a short repeating CAG sequence within the *Huntingtin*[1] (Htt) gene that tends to get extended during cell division. This gene can have as few as 6 of these CAG sequences, but there's a chance with each generation for the number of CAG copies to increase. Once it exceeds 35 or so, people can start to have symptoms of Huntington's disease, with higher copy counts resulting in earlier and more severe disease progression.
1: https://en.wikipedia.org/wiki/Huntingtin
Although any given familial lineage of Huntington's disease will likely die out after a few dozen or a few hundred generations, that won't eliminate Huntington's disease, because new familial lineages will continue to evolve.
There's another question we might ask: why doesn't the high-normal CAG repeat count disappear? There does not appear to be any harmful effects on the individual from having at most 35 CAG copies, but they can start to manifest one or more generations later as more CAG copies accrue. Because several generations separate the high-normal repeat genotype from any harmful survival effects, the evolutionary pressure selecting against high-normal repeats is severely weakened. So we reach an evolutionary equilibrium in allele frequency from (a) the de novo copy number mutation in the Htt gene CAG repeat area, (b) genetic drift, and (c) very weak natural selection against high CAG copy counts.
Comment by scarf_spheal at 29/11/2024 at 16:46 UTC
3 upvotes, 0 direct replies
There’s a few aspects to genetic diseases that can keep them around.
First, they can be recessive meaning people can carry the gene for the disease but not have any symptoms. They will only have kids with the disease if they partner up with someone that either has the disease or is a carrier.
Second, there is something called variable expression and reduced penetrance. Variable expression means that the disease can vary based on other genes the person has or environmental factors. With penetrance, sometimes the gene is present but the disease is not and it’s unknown why.
Third, late onset. Sometimes diseases are only pathological until later in life after reproduction. As far as evolution is concerned the important event of reproduction already happened so it won’t weed out the gene.
Lastly, mutations still occur so even if every single person that has the mutation no longer reproduces. The gene could arise again due to random chance.
Comment by Ravager135 at 29/11/2024 at 17:57 UTC
3 upvotes, 0 direct replies
If I recall correctly (and please feel free to correct), doesn't Huntington's severity depend upon the number of repeats (CAG I think) in the DNA? Is it not probable that people can carry a low threshold of repeats and either be asymptomatic or develop symptoms later in life versus those with far more repeats and develop symptoms that are worse in severity and at a younger age?
Comment by melibelly42 at 29/11/2024 at 22:00 UTC*
3 upvotes, 0 direct replies
There are three main reasons we currently know of:
1. Huntington’s Disease is caused by a repeat of the nucleotides CAG within the Huntington gene. CAG happens to be a sequence of nucleotides that our DNA copying enzyme can accidentally get “caught” on and make extra sequences of when DNA is replicating. We know that humans with over 40 copies of CAG in their Huntington gene will develop the disease.
2. However, a higher number of CAG repeats (until the level where you get the disease) is associated with higher intelligence, so in addition to the increased likelihood of copy number mutations, more repeats are likely to have been selected for as humans evolved.
3. This is a neurodegenerative disease with onset after prime reproductive years, so although it is detrimental to have parents that have less capacity to assist you as you age, a combination of social structures that can step in for support and higher intelligence through the unaffected part of the family tree are thought to have been enough to not stop the gene from continuing to reproduce.
Comment by CompoundT at 29/11/2024 at 14:52 UTC
8 upvotes, 0 direct replies
I don't think grandparents were the answer, I think having more children was the answer. This way not everyone gets the genes for Huntington's disease. Also raising children until they are relatively self sufficient doesn't take very long. Then they are recruited to help run the household and care for themselves and siblings.
Comment by victorianfollies at 29/11/2024 at 15:52 UTC*
3 upvotes, 2 direct replies
Huntington’s (chorea, or St Vitus dance) was among the first hereditary illnesses to be mapped, giving rise to the first standardised pedigree charts in the mid-19th century. The problem is, anything before gene testing was available was essentially guess work, based on reported symptoms and pedigree charts (which, before paternity tests and long-term follow up, were shaky at best). So, aside from the age of onset issue described by others, as well as the possibility that people died of other causes before showing symptoms, a lot of people wouldn’t know that they have a family history.
Comment by Daenerys_Stormborn at 29/11/2024 at 15:10 UTC
2 upvotes, 0 direct replies
There’s an element of luck (good or bad) in what gets maintained. The disadvantage, as others have mentioned is small in terms of reproductive success. Also remember that no mutation is existing in isolation. The family that is disadvantaged by a huntingtons mutation may have had other variants in unrelated genes that were advantageous to reproductive success. Or they had more offspring for non evolutionary reasons. As a result, through a combination of luck and extenuating factors, the mutation can hang around at a low frequency in the gene pool despite having only negative evolutionary value.
Comment by moccasins_hockey_fan at 29/11/2024 at 15:35 UTC
2 upvotes, 0 direct replies
Huntington's disease doesn't manifest until long after the individual has reached reproductive age. Therefore people don't know that they are putting their kids at risk.
A better example for your hypothetical is sickle cell and hemophilia. Those manifest in childhood. An individual could decide to not have kids because they are at risk of inheriting a known medical condition. But unless you plan on some sort of unethical eugenics program, you can't prevent humans from reproducing.
Comment by Money_Display_5389 at 30/11/2024 at 00:08 UTC
1 upvotes, 0 direct replies
Well, in addition to extended lifespans, only now showing the ugly side of Huntingtons. The gene was only isolated in 1993, so it's only been 30 years since we have definitively been able to predict Huntingtons. Before we did realized it was passed from parent to child, but it's still a 50/50 chance.
Comment by Batavus_Droogstop at 01/12/2024 at 08:37 UTC
1 upvotes, 0 direct replies
I don't know about huntingtons specifically, but some recessive diseases have an advantageous effect for carriers. For example B-thalassemia carriers are less likely to get malaria and cystic fibrosis carriers may be less likely to get tuberculosis. Nowadays that's not a real advantage, but some time ago, that may have been a net advantage as you would otherwise lose more kids to TB than you would due to CF.
Comment by MurseMackey at 01/12/2024 at 14:38 UTC
1 upvotes, 0 direct replies
You only have to live long enough to reproduce for these things to be passed on. Given that the disease typically doesn't present itself blatantly until around the early thirties (with exceptions), a lot of individuals will already have had children by that age.
Comment by Visible-Shopping-906 at 01/12/2024 at 17:59 UTC
1 upvotes, 0 direct replies
Huntington’s disease and other generic diseases can arise from de novo mutations (from scratch). The gene encoding Huntingtin, the protein associated with diseases has a “CAG” repeated region that is prone to mutation. Over generations mutations can accumulate in this region. This makes it so that while inheritance is a big factor, the de novo aspect also plays a part.
Comment by tacertain at 01/12/2024 at 18:17 UTC
1 upvotes, 0 direct replies
It talks about various ways that certain genetic diseases also have benefits (sometimes it's obvious, like sickle cell anemia and malaria - other times less so). It specifically mentions Huntington's.
Comment by Izawwlgood at 29/11/2024 at 16:34 UTC
1 upvotes, 0 direct replies
Huntington's is also a disease that doesn't strike until significantly after reproductive age, meaning it won't negatively impact fecundity outside removing long term caretakers.
In social organisms loss of longevity without impeding reproductive potential may minimally impact offspring fecundity.
Comment by sciguy52 at 29/11/2024 at 22:56 UTC
1 upvotes, 1 direct replies
Because of the very reasons you stated. The disease onset is later in life and people have already reproduced. In an evolutionary sense that person did what evolution "wants" which is to reproduce and raise young. What happens to you after that is not that big of a concern. If Everyone died at 50 that is fine as far as evolution is concerned, they all typically reproduced and raised their young. On the other hand you are assuming knowledge the local village did not have. They knew this person became infirm and died and that is all. They didn't know why. For the vast majority of people who died of disease they did not know the exact reason. So as far as those historic communities were concerned someone dying in their 50's was a very common thing, and why they died was a mystery to them.
Grand parents may have been helpful in raising the young but they are not a necessity. Go way way back in human history and few lived to be grand parents given the age of mortality was so young. So using the evolutionary argument, if grand parents was a selected trait, namely that people lived longer to help care then you would expect people to live longer. But that is in fact not what you see in the historic past. Few lived to that age and thus you can't say having grand parents around is someting evolution selected for. It just something that happened sometimes and they were useful but not necessary. In this case it is not an evolution thing.
Comment by whatshamilton at 29/11/2024 at 22:00 UTC
0 upvotes, 0 direct replies
There are two genres of evolution, if you will. There’s that which is fatal before sexual reproduction or causes inability to sexually reproduce. You already pointed out Huntingtons doesn’t fall within that, because it presents after the age of reproduction and by the time you know, genes are passed. Then there’s that which makes you a less desirable partner socially. Even if the giraffe with the short neck doesn’t starve TJ death, other giraffes wouldn’t want to pick it to father their offspring. I think that’s what you’re getting at — why did Hunter-gatherers reproduce with people who came from families that kept presenting with Huntington’s? And the answer is that Hunter-gatherers didn’t have genetics departments explaining hereditary disease. They had religion and superstition and ritual. That family where half the kids get sick when they get old may be unlucky, but unlucky isn’t enough to preclude all reproduction. Plus they didn’t even know how babies are made. They didn’t know not to have sex with the unlucky kids if they didn’t want unlucky kids