So is the second X chromosome in women supposed to be an exact copy of the first or do they differ? That's fascinating to me all by itself, and more so that some genes in the dupe can reinforce the first even though the rest of the chromosome is suppressed.
EDIT: Ah, wikipedia explains that the two X chromosomes in a standard-issue woman come from the mother and paternal grandmother, and then ... "Early in embryonic development in females, one of the two X chromosomes is randomly and permanently inactivated in nearly all somatic cells (cells other than egg and sperm cells). This phenomenon is called X-inactivation or Lyonization, and creates a Barr body. If X-inactivation in the somatic cell meant a complete de-functionalizing of one of the X-chromosomes, it would ensure that females, like males, had only one functional copy of the X chromosome in each somatic cell. This was previously assumed to be the case. However, recent research suggests that the Barr body may be more biologically active than was previously supposed." Which must be related to the EXITS that the OP refers to.
Being a male, I'm troubled by the fitness of the Y-chromosome over the generations. It seems to me that it can only accumulate errors and mutations. However, I suppose the same could be said about the mitochondria that come exclusively from females. This partial double-X scheme seems like a useful way of mixing up traits intrageneration and maybe strengthen healthful cell behaviors.
> It seems to me that it can only accumulate errors and mutations.
Except some of those mutations can be useful – some deadly, but some could be selected for as one's environment/niche shifts. That's evolution and selection in a nutshell. Not all mutations are bad and not all bad mutations are always bad.
As a parent of a daughter with Fragile X Syndrome, I'm glad she has two X chromosomes. The "good" one in her case helps reduce the severity of her symptoms. Males with the Syndrome face far more difficulties as their lone X chromosome is the one with the mutations.
Yes, truly over the long haul, the fittest survive - helpful mutations account for all survival thus far.
I just envy what I interpret as an intragenerational bolstering of genetic traits that females have, assuming the EXITS thing is truly what's going on. They don't have to wait a generation to perhaps select out the bad, they get to do it on the fly.
It's a conservative strategy -change from one generation to another will likely be moderated/averaged by the influence of the second X chromosome for female offspring. Alternatively, single copy governed traits (as in males) mean greater ability to adapt (at a higher mortality rate) and those successful remaining males can propagate their single X chromosome (new and improved, thank you) to their daughters. It's a cool pattern of balances, IMHO.
Hmm. Are you saying that men's imputing of adaptations to their one X chromosome is somehow more concentrated/effectual than the adaptations a woman imputes to her 2 X chromosomes? What is the mechanism and how did you draw that conclusion? Because she only passes one along?
It seems to me that chiefly the non-suppressed X chromosome in females would see action by its workings and thus accumulate adaptations.
Females have both X chromosomes active, but only one copy per cell due to Barr body deactivation. Some female cells have one copy active, others utilize the other copy.
This scheme can lessen certain X-linked genetic disorders in women since not all cells will be affected.
Fascinating, did not know that "loss of Y" was possible in vivo, not just evolutionarily across spans of generations. This led me to finding out that loss of Y is tentatively tied to Alzheimer's, and wondering if chronically low testosterone levels are possibly linked to loss of Y.
This is why all calico cats are female. Fur color comes from the X chromosome. The different color areas are descendant from different initial somatic cells.
Um the X chromosome in a women comes from the mother and the paternal grandmother and grandfather because there is crossover between X and Y chromosomes (albeit very little).
There's no need to worry about the Y chromosome disappearing because it's remarkably stable. This makes sense -- males with Y mutations die out and men are extremely good at producing offspring. This only good Y chromosomes are passed on.
Nevertheless, the genes on the Y chromosome are like any other and if the Y chromosome were to disappear, natural selection would still push for a 50/50 sex ratio. The Y chromosome itself isn't necessary to make a male -- its genes can be spliced onto the X chromosome and function properly. Thus, if we saw loss of Y, we would likely see a 50/50 gender split but now based on presence of the SRY gene.
> Thus, if we saw loss of Y, we would likely see a 50/50 gender split but now based on presence of the SRY gene.
If that were to occur, we'd get into more X-SRY X-SRY situations much more often though, right? Sounds unhealthy, I'd prefer to keep the Y separate and intact for as long as possible. :)
It's worth pointing out that since Barr body deactivation occurs later in development, some female cells have one of the X chromosomes active, while other cells have the other one active.
So is it wrongheaded to think all women are a bit of a chimera, then? It would seem females would benefit for the most part from this chromosomal arrangement healthwise than males, more diversity.
That term is reserved for organisms comprised of cells that derived from two or more zygotes, but you've definitely got the right line of thinking. Some of the cells of a female will express the genes from one of the X chromosomes, whereas the rest will utilize the other. It certainly can lessen the ill effects of certain X-linked diseases.
Some of the other posters in the thread already mentioned calico cat fur coloration. The underlying mechanism is the textbook example of Barr body inactivation. You should check it out on Wikipedia.
> Being a male, I'm troubled by the fitness of the Y-chromosome over the generations. It seems to me that it can only accumulate errors and mutations.
One possible safety hatch that comes to mind is that it's possible for XX males to exist. There's only one gene on the Y chromosome which has anything to do with male development, the SRY gene, which causes the proto-gonads to develop into testes (all male development following that is the result of the testes producing androgens). During meiosis, it's possible for the SRY gene to break off of the Y chromosome on one sperm and make its way into the X chromosome on the other sperm. When this happens, it's called de la Chapelle syndrome [0].
So if the Y chromosome eventually becomes unusable, we might end up in a future where males are created by inducing de la Chapelle syndrome in vitro by splicing an SRY gene into the zygote.
The only problem is that males with de la Chapelle syndrome are sterile, but I'm sure that if we get to the level of technology where this kind of gene splicing is commonplace, we can come up with some kind of hack to get around it. It's been speculated for a while that eventually we'll develop the technology to make one egg fertilize another in vitro, resulting in a healthy XX zygote, so that's one way (though the eggs wouldn't come from people with de la Chapelle's... which means we wouldn't need to induce it in the first place... so female-only world it is).
Which is why human engage in mate selection and are great at multiplying. Plus innate abity to advance technology. We'll engineer ourselves to survive.
Or nuke everything, whichever comes first. Heh.
Edit: not to knock off the downvotes, if they're due, they're due. But may I enquire as to why I am being downvoted?
I didn't downvote you because you replied to me, and apparently I can't.
In my opinion, you didn't add much to the conversation and then with that last crack you did a snarky mic drop where you totally blew it.
I like to ask questions, perhaps with a careful dash of snark if I think I can flash out with some wit, and keep the conversation going.
For example, I might reply to you,
> Which is why human engage in mate selection and are great at multiplying.
Are we really selecting mates based on any useful criteria? It seems random to me, rarely based chiefly on reproductive fitness.
... and then someone smart chimes in with a technocratic article on how we DO (for the most part) select based on X number of traits that increase the survivability of our offspring - and we roll on for a bit more and I learn new things.
I didn't mean to sound snarky, it was more of the pessimist in me. But chiefly an optimist. I trust evolution is doing the right thing. But that is indeed a weak argument, seeing as it's not supported by either more philosophy or science.
I do apologise for how it came through, in was on mobile and didn't have time to put in more prose.
I should have brought in more facts into my own argumet to spark a discussion. I'll take the critism to mind and adjust.
I didn't downvote you, but I think it's pretty obvious:
> Or nuke everything, whichever comes first. Heh.
is the why. Casual amusement at nuclear holocaust/extinction doesn't tend to get a lot of upvotes on HN.
Plus, it didn't make any sense: 1) a nuclear war wouldn't involve nuking everything under any plausible scenario; 2) you could direct every nuclear missile on earth at just the US (including the US arsenal) and still not manage to kill all the people in the US with either the initial blasts or the fallout, which is another way of saying that not only can we not nuke everything, but we couldn't even eradicate ourselves with nuclear war if we wanted to for some reason (much less wipe out the planet, much less wipe out all of humanity, that's all beyond far-fetched).
Although the title seems more appropriate for a ponderous meditation on a great mystery, the article is pretty concise and does cover the case for a specific mechanism. I think the HTML title ("A reason why cancer is less common in women") is better.
I agree, but only because questions so often go bad in titles that I now avoid them on principle. This is a rare situation where the question asked in the title is answered in a non-obvious way, so I can't actually point to anything wrong with titling this with a question.
Does anyone know how the X-inactivation thing works with the popular explanation for why women are less likely to be color-blind than men (ie: They have two copies of the gene for sensitivity to light of that wavelength, so both copies must be mutated in order to be insensitive)?
According to this (and contrary to the article?), X-inactivation is randomized between cells, so women carriers of the color blindness mutation have half the number of correctly functioning cone cells.
1. Imagine the retina as a field of neurons that are receptive to light. Imagine different types of neurons are sensitive to different types of light (RGB). Each person has two copies (or alleles) of the R, G, and B genes. The R & G genes are on the X-chromosome.
2. In a color-blind person, the R & G genes merge to form a R-G allele that is sensitive to some red-green combination. Thus, men who carry this R-G gene have cells that express B and R-G genes and thus are red-green colorblind (they can't distiguish between the two because they only have one type of receptor for the two). Remember they only have one copy of these R and G genes.
3. Women might carry the R-G allele, but in those cases their retina as a whole display R, G, B, and R-G. These people are known as heterochromats can can distinguish colors better than normal people. Note that X-inactivation leads to cells even having R-G allele, or R or G gene.
4. It's rare for a woman to have two R-G alleles. When they do, they are red-green colorblind.
In (3), are you describing what I've sometimes heard called tetrachromat? Is that now confidently considered extant? Last I'd heard, it was an exciting, but only slightly substantiated, theory, but I'd love to see more about it!
Yes, I think you are right. I thought I remember it being heterochromat, but looking online all references seem to be to tetrachromat. In terms of evidence, I think prevalence is there, but there were some papers where they actually tested color perception differences (at least from wikipedia).
But the gene for the pigment is on the X-chromosome which is why women can have both variants and thus be tetrachormatic. But this would require both X's to be active unless this gene is also in the non-inactivated region.
I believe it is exactly the mechanism described in the article: X-inactivation is incomplete. Some of the genes on the "inactivated" chromosome remain active.
What is new in this article is that they connected specific genes known to be active, to genes relevant for cancer. In other words, the theory was that the remaining-active genes helped avoid cancer, color-blindness, etc., and the article provides strong evidence supporting that in the area of cancer, the genes are the right ones.
Wikipedia suggests there are other theories too, like inactivating picking the "best" of the two options non-randomly, and the mosaic effect - it isn't the same X-chromosome inactivated everywhere, so e.g. some retinal cells might have one X and others the other.
> X-linked recessive traits are expressed in all heterogametics, but are only expressed in those homogametics that are homozygous for the recessive allele. For example, an X-linked recessive allele in humans causes haemophilia, which is much more common in males than females because they are hemizygous (see zygosity) and therefore express the trait when they inherit one mutant allele. In contrast, a female must inherit two mutant alleles, a less frequent event since the mutant allele is rare in the population.
You've just restated the popular explanation, right? You haven't addressed aetherson's question about how to square this explanation with X-inactivation in women.
If this is talking about a prostate vs breath cancer dichotomy. The reason is prostate cancer kills much older men than breast cancer kills women. Women in their 40s routinely die of breast cancer but that's pretty rare for a man in his 40s to die of prostate cancer.
So saving a man's live fron prostate cancer means he dies at 75 instead of 70 and but saving a women's from breast cancer means she dies at 65 instead of 45.
By this reasoning children's diseases should get even more publicity and money, and I'm aware of nothing in that area that comes even remotely close in terms of funding and awareness campaigns.
The breast cancer movement was started because at the time, male-only cancers (such as prostate and testicular cancers) were getting far more funding and research, while breast cancer was essentially being ignored despite being at least an order of magnitude more common.
That it's more common has probably made it easier to do research on once it gained sufficient visibility and funding.
Edit: not to mention the perception of females as a weaker sex. Socially, society is mirroring male behavior in terms of protection of females. It'll switch and balance itself out in due time. Historically I think makes died more often to work or war, females to sickness. Today these boundaries are blurring, but (socio)evolution is a patient turtle.
Any facts to back that up? The story I hear more often [1] is the other way around. More men in medical studies, more often male animals in studies etc.
The lack of inclusion of women and minorities has historically been such a problem that it is now a term and condition of many awards from HHS:
"In addition, several OPDIVs have policies concerning the inclusion of women, minorities, and children as subjects in their grant-supported research. These policies, which implement Section 492B of the PHS Act, 42 U.S.C. 289 a-2, require that women and members of minority groups and their subpopulations be included in OPDIV-supported research projects involving human subjects, unless a clear and compelling rationale and justification establishes that inclusion is inappropriate with respect to the health of the subjects, the purpose of the research, or other circumstances. When these policies apply (as specified in the funding opportunity announcement), the applicant is required to address inclusion of these groups in the application narrative, and the applicant’s plans will be assessed as part of the objective (peer) review process. Failure to comply with this policy or to adequately address use of human subjects and animals may adversely affect the score for technical merit, which may result in the OPDIV not making an award."
I immediately guessed that this would be the explanation before reading the article. An important corollary hypothesis (that would exclude things like androgen effects) would be to do a statistical analysis on XY-women and see if they have similar cancer rates as men.
That is, if they can round up a representative sample. If the lack of Swyer syndrome (XY-women) published works is telling of anything, it's that cases are very rare.
Humans have a "tumour suppressor gene" called p53 which helps reduce the occurrence of cancers. Elephants (not quite whale size, but still pretty big!) have been shown to simultaneously express 20 variants of p53 which is thought to (at least partially) account for the lack of an expected increase in incidences of tumours given their sheer number of cells.
One of the theories is that for whales, they are so large their cancer gets cancer and dies before the cancer is large enough to effect them. Or genes prevent them from getting it, etc.
There are a number of ways that whales are different from humans, and there is no reason that the cancer scaling with mass in humans is invalidated by whales.
Human men are pretty similar to human women, whales are kind of different. So the number of cells alone is quite a good way to differentiate men and women, not so much humans and whales.
My first thought was that the opposite was true. The immune system attacks healthy cells, increasing inflammation, thus stress. Thereby lowering the normal immune system and allowing cancer cells to flourish.
Unless you're talking about all-encompassing diseases (I can't think of any off the top of my head). Otherwise, I don't think Celiac/MS/Diabetes is fighting any cancers.
The problem is if your immune system is too permissive it's leaving around damaged DNA lines that can later become even more damaged in a cancer kind of way.
Hypothesis: it's socially more acceptable for men to not care for their body as much as women do, eat worse, drink more soda and beer, etc. leading overall to more sugar(y) foods and more inflammation?
Also, men don't get multiple periods in their lives when they are checked out for every condition under the sun. My wife's health was given a thorough run down when she was pregnant and a bunch of things caught and fixed -- like her hypothyroidism. I go regularly to my physicals and had never been checked out so much.
I ended up demanding that I too get tested for some of these things, and the doctors caught that I also had an asymptomstic but more serious autoimmune thyroid disease. Had I been a woman, I would have caught this during pregnancy check ups, and been treated. Instead I had to demand it.
Now of course I think it's fine for pregnant women to be given priority but we need to realize that men don't get the equivalent treatment and thus encourage programs to get men in to the doctors, thoroughly tested, and treated. Make it part of a pre-birth check up for fathers. After all, once the baby is born, it would be nice if they had a father.
Social anecdotal evidence from the United States: according to TV commercials the most pressing female health problem is breast cancer, while the most pressing male health problem is Erectile dysfunction.
I think its more that society impose pressure on women to care how they look and being healthy, while imposing similar requirement on men to care about their ability to raise money. Dating site statistics shows a very strong correlation for successful profiles that follows those gender roles, where a man who focus more on about taking care of their body than their carer has a negative correlation, and women who focus more on their carer than taking care of their body has a negative correlation.
Genetic differences between males and females may account for some of the imbalance in how often people get sick, but incentives may also account for some. The article don't really explore that.
Because men receive worse medical treatment. Just compare how prostate and breast cancer are promoted. It also corresponds with other statistics like life expectancy, medical expenses, disposable income...
Too bad you didn't read the article! The work the scientists did led to much more interesting breakthroughs that that. I learned several new things (x-inactivation and the "EXITS" exceptions to the phenomenon).
Yeah, but it's also a bit unfair for a recap of all of gender based differences in all-cause cancer epidemiology in an article about a specific breakthrough :)
On the flip side, studies have shown that women are less likely to be taken seriously when bringing a medical concern or complaint to a doctor. Which might suggest that women are under-diagnosed compared to men.
However personal experience tells me women are more likely to go to the doctor in the first place whereas men have more of a "it'll fix itself" attitude
Recall a study done on psychologists (think it was done in Sweden).
Men were significant less likely to be taken serious and admitted. However those few who are admitted are then taken more serious, and get more direct treatment than women. From a cultural perspective, men are viewed as always healthy, and in the exceptional case where its proven false then they are expected to be restored back to the norm. Women get the opposite cultural treatment, where they are easy accepted as sick but then the health system gives up and don't expect them to be able to be restored back.
Are you suggesting men don't seek medical treatment therefore it's their fault for getting sick?
Girls often don't want to become programmers, and, as I know it, we don't say "It's their fault". We just raise the issue and everyone is fighting to make them want to become programmers.
It's way past time we apply the same reasoning to men's problems as women's problems. Males not seeking medical treatment could be because they're not aware of it (i.e. not enough funding for male diseases as female preventive programs). Or it could be because males are more suicidal about life, because they get the short end of the stick in pretty much all countries, despite the way it is framed in statistics, and we should equally fight for that. In any case, any statistics which leads to 6-year-shorter life expectancy denotes a very acute problem, for which funding should be given in equal level as for women's equality.
As a man myself it is pretty crazy to me how many men will ignore health problems to avoid going to the doctor. I am in the UK so it doesn't even cost me anything.
Yet I have had male colleagues laugh/take the piss out of me for going to the doctor. Yet I think I am the only male in the office who doesn't have some kind of chronic (or close to it) condition at 32. It seems everyone at work has back pain or some other chronic pain because they ignored it when it could have been solved easily. Now some of them need surgery for trapped nerves or slipped discs but don't treat it still! Stupidity IMHO.
The worst I know of is a guy I used to work with lost his testicles because he ignored pain and a lump which was cancer! He is lucky to still be alive.
Except when they're both required and neither is sufficient, as in this case. In preventative medicine, in order to have quality one must have quantity.
I found a really excellent answer to this question in one of my university evolution textbooks [1]. The fact that men generally die sooner than woman (in humans) has been well studied and we've come to a fairly decent answer.
--
Why do people die?
The answer to this mystery has been partially solved by senescence theory (Williams,
1957). Senescence is not a specific disease, but rather the deterioration of all bodily mechanisms as organisms grow older: Senescence theory starts with an interesting observation:
The power of natural selection decreases dramatically with increasing age. To understand
why this occurs, consider a twenty-year-old woman and a fifty-year-old woman. Selection
operates far more intensely on the younger woman, since anything that happens to her could
affect most of her future reproductive years. A gene activated at age twenty that weakened
a woman’s immune system, for example, could damage her entire reproductive capacity. If
the same damaging gene became activated in the fifty-year-old instead, it would have
almost no impact on the woman’s reproductive capacity. Selection operates only weakly on
the older woman, since most or all of her reproduction has already occurred (Nesse &
Williams, 1994).
Williams (1957) took this observation as a starting point and developed a pleiotropic
theory of senescence. Pleiotropy is the phenomenon whereby a gene can have two or more
different effects. Let’s say that there is a gene that boosts testosterone in men, causing them
to be more successful in competing with other men for status early in life, such as in their
twenties and thirties. But the elevated testosterone also has a negative effect later in life—
increasing the risk of prostate cancer. This pleiotropic gene can be favored by selection-—
that is, it increases in frequency in subsequent generations—because the early advantage in
status gains for men outweighs the later cost in lowered survival due to prostate cancer.
Through this pleiotropic process, we have evolved a number of genes that help us early in
life but cause damaging effects later in life, when selection is weak or absent.
The pleiotropic theory of senescence helps to explain not only why our organs all wear
out at roughly the same time late in life, but also why men die younger than women—
roughly seven years earlier on average (Kruger & Nesse, 2006; Williams & Nesse, 1991).
The effects of selection operate more strongly on men than on women because the reproductive variance of men is higher than that of women. Stated differently, most fertile women
reproduce, and the maximum number of children they can have is sharply restricted—
roughly twelve, for all practical purposes. Men, in contrast, can produce dozens of children
or be shut out of reproduction entirely. Because men have greater variability in reproduction, selection can operate more intensely on them than on women. In particular, selection
will favor genes that enable a man to compete successfully for mates early in life to be one
of the few who reproduces a lot or to avoid being excluded entirely.
Selection for men’s success in mate competition will be favored, even if it means
that these genes have detrimental effects on survival later in life. Even though men can and
sometimes do reproduce for a longer period of time than women. Senescence theory explains
why these later reproductive events will have a much smaller impact than events occurring
earlier in life for men. Genes will be selected for early success in mate competition more
strongly in men than in women, at the expense of genes that promote survival later. This
strong selection for early advantage produces a higher proportion of pleiotropic genes that
cause early death. As one researcher noted, “it seems likely that males suffer higher mortality
than do females because in the past they have enjoyed higher potential reproductive success,
and this has selected for traits that are positively associated with high reproductive success but at a cost of decreased survival” (Trivers. 1985, p. 314). Men, in short, are
“designed” to die sooner than women, and the theory of senescence helps to solve the
mystery of why.
In summary, selection is most potent early in life because any events that happen early
can affect the entire span of a person’s reproductive years. As people get older, however, the
power of selection weakens. In the extreme case something that happened to you in old age
right before you died would likely have no effect on your reproductive capacity. This means
that selection will favor adaptations that give beneficial effects early in life, even if they
come with heavy costs later on. These heavy costs cumulate in old age, resulting in the deterioration of all body parts at roughly the same time. In this sense organisms can be said to
be “designed” to die.
--
The authors are pushing the X-linked recessive inheritance
hypothesis https://en.wikipedia.org/wiki/X-linked_recessive_inheritance , which by itself is fine but by itself does not paint the whole picture. The theory does not take into account how genes on the Y chromosome can affect the expression of other genes. For instance, a single gene on the Y chromosome can affect the expression of thousands of other genes across the whole genome.
[1] Evolutionary Psychology: The New Science of the Mind (4th Edition) by David Buss, pages 101-102
I agree. However, most of the info. I've read comes from "health journalist" Bill Sardi. Despite the sound ideas, he is still brushed off as a crack-pot. Nevertheless, I'm betting on the "over-mineralization" theory of aging.
I doubt it will ever become accepted. People seem to like to think in terms of genetics (because that's what the "experts" talk about most of the time) and "hi-tech" dreams (e.g.nano-bots killing off cancer). Even when epigenetics is mentioned, they still get it wrong when applied to age-related illnesses.
There is reasonably good evidence that excess iron is a risk factor in heart disease, which may be at least part of the reason that pre-menopausal women have less risk than men and post-menopausal women. But there doesn't appear to be a clear link to cancer.
EDIT: Ah, wikipedia explains that the two X chromosomes in a standard-issue woman come from the mother and paternal grandmother, and then ... "Early in embryonic development in females, one of the two X chromosomes is randomly and permanently inactivated in nearly all somatic cells (cells other than egg and sperm cells). This phenomenon is called X-inactivation or Lyonization, and creates a Barr body. If X-inactivation in the somatic cell meant a complete de-functionalizing of one of the X-chromosomes, it would ensure that females, like males, had only one functional copy of the X chromosome in each somatic cell. This was previously assumed to be the case. However, recent research suggests that the Barr body may be more biologically active than was previously supposed." Which must be related to the EXITS that the OP refers to.
Being a male, I'm troubled by the fitness of the Y-chromosome over the generations. It seems to me that it can only accumulate errors and mutations. However, I suppose the same could be said about the mitochondria that come exclusively from females. This partial double-X scheme seems like a useful way of mixing up traits intrageneration and maybe strengthen healthful cell behaviors.