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Angela
05-12-16, 17:28
The results seem to hold over four generations and four geographic areas.

See:
http://biorxiv.org/content/biorxiv/early/2016/03/08/042788.full.pdf

"Higher paternal age at offspring conception increases de novo genetic mutations (Kong et al., 2012). Based on evolutionary genetic theory we predicted that the offspring of older fathers would be less likely to survive and reproduce, i.e. have lower fitness. In a sibling control study, we find clear support for negative paternal age effects on offspring survival, mating and reproductive success across four large populations with an aggregate N > 1.3 million in main analyses. Compared to a sibling born when the father was 10 years younger, individuals had 4-13% fewer surviving children in the four populations. Three populations were pre-industrial (1670-1850) Western populations and showed a pattern of paternal age effects across the offspring's lifespan. In 20th-century Sweden, we found no negative paternal age effects on child survival or marriage odds. Effects survived tests for competing explanations, including maternal age and parental loss. To the extent that we succeeded in isolating a mutation-driven effect of paternal age, our results can be understood to show that de novo mutations reduce offspring fitness across populations and time. We can use this understanding to predict the effect of increasingly delayed reproduction on offspring genetic load, mortality and fertility."

It seems that with all the advantages of modern medicine, the disadvantages can be ameliorated.

That wasn't the case in prior eras. That means that this social construct, where older men who have acquired more wealth and power have more access to women, was actually not very beneficial in terms of the overall health of the population, yes? Their genes would not, in those cases, be disproportionately being passed down, so how does impact our understanding of the processes of the past?

srdceleva
05-12-16, 19:36
My father was born when his father was 50, he has 5 children more than any of his siblings( he's the youngest) and is 65 years old now and is healthy thank God.

Tomenable
05-12-16, 19:49
This claim about "less evolutionary fitness" of children of older fathers is utter nonsense, because prior studies have shown a long-term trend of correlation between higher paternal age at offspring and increasing average IQ of the population.

Maybe precisely these de novo genetic mutations are influencing brain function and contributing to higher average IQ.

If by "evolutionary fitness" they mean being well-adapted to R-selected simple jungle lifestyle, then maybe they are right.

But such model of early reproduction did not lead to adaptation to modern civilization and to high IQ societies.

People evolved higher IQ in areas where couples tended to marry and to have children long after 20. North-Western Europe is where parents tended to be older than anywhere else in the world during the last several centuries. Is North-Western Europe "genetically messed up" because of that, compared to areas where people reproduce as teenagers (for example Africa)?

What actually is this "fitness" anyway ???

I have read somewhere that all Eurasians have much lower fitness than Sub-Saharans because they are less genetically diverse, descended from a bottlenecked population (the Out-of-Africa Tribe), and because they mixed with Neanderthals (mixing with Neanderthals supposedly - quote - "lowered fitness of Non-Africans by 0.5% comapared to Africans").

Tomenable
05-12-16, 20:06
That means that this social construct, where older men who have acquired more wealth and power have more access to women, was actually not very beneficial in terms of the overall health of the population, yes?No. As I wrote, it is utter nonesense. And it is not a "social construct" but an evolutionary trend.

Older men who acquired wealth and power were boosting the average IQ of the population by passing their genes.

That is how we got from ~70 points to ~100 points between the Paleolithic and the 21st century.

"De novo genetic mutations" is what drives the evolution forward, by the way...

In other words: populations where people reproduce as teenagers are not evolving.

LeBrok
05-12-16, 20:48
This claim about "less evolutionary fitness" of children of older fathers is utter nonsense, because prior studies have shown a long-term trend of correlation between higher paternal age at offspring and increasing average IQ of the population. It is only correlation. The cause of rising IQ and age of parents, is related to rising technological advancement and wealth of societies. Kids get extensive education couple of decades long, learn many games and are bombarded by non stop information. This trains brains increasing IQ. The same well off societies tend to have kids later in life, unlike HGs who start at age of 12-14, and not much later for simple farmers at 15.



Maybe precisely these de novo genetic mutations are influencing brain function and contributing to higher average IQ.

If by "evolutionary fitness" they mean being well-adapted to R-selected simple jungle lifestyle, then maybe they are right. But Sub-Saharan model of early reproduction did not lead to adaptation to modern civilization and to high IQ societies.

People evolved higher IQ in areas where couples tended to marry and to have children long after 20. North-Western Europe is where parents tended to be older than anywhere else in the world during the last several centuries. Is North-Western Europe "genetically messed up" because of that, compared to areas where people reproduce as teenagers (for example Africa)?

What actually is this "fitness" anyway ??? We know that late age of fathers causes more mutation in sperm and increases frequency of down syndrome in kids for example. Generally speaking, by nature of things, most mutations are negative than positive therefore will affect offspring survival negatively.

firetown
05-12-16, 20:54
Higher IQ amongst children of older fathers can easily come from the fact that rather than spending time teaching sons sports, older men prefer to sit down with the children and share knowledge if not "wisdom".

LeBrok
05-12-16, 20:55
No. As I wrote, it is utter nonesense. And it is not a "social construct" but an evolutionary trend.

Older men who acquired wealth and power were boosting the average IQ of the population by passing their genes.

That is how we got from ~70 points to ~100 points between the Paleolithic and the 21st century.

"De novo genetic mutations" is what drives the evolution forward, by the way...

In other words: populations where people reproduce as teenagers are not evolving.And how do you explain the progress we did since swinging on trees and barely walking Lucy 3 million years ago to Neolithic? We were all hunter gatherers having first kids at 12, and not living longer than 35 years. For most of farming existence not much better, kids at 15 and lifespan of 40 years.

firetown
05-12-16, 20:56
Higher IQ in children of older fathers can easily come from the fact that rather than teaching their sons sports, older men may prefer sitting down with their kids sharing knowledge if not "wisdom".

Tomenable
05-12-16, 21:20
by nature of things, more mutations are negative than positive

Not true.

Mutations are random which means that the chance of positive to negative will be 50 to 50.

Most of mutations are in fact neutral and have no effect on anything.

Real proportions are most likely something like 90% neutral, 5% positive and 5% negative.

=======================

The paper did not mention positive mutations because it is now "politically incorrect" to admit that humans are still evolving (Henry Harpending and Gregory Cochran wrote that "people in different parts of the world are still evolving, and evolving differently" - they were labeled as "racists"). This paper is another attempt to disparage "Cis White Male R1b Patriarchs".

"Cis White Male R1b Patriarchs" are not my words. One of moderators coined this term some time ago.

Angela
05-12-16, 21:30
IQ doesn't get higher from teaching. It's innate. Also, even if that could happen, i.e. IQ getting higher because of better teaching from older fathers, any speculative higher IQ in the children of older fathers is irrelevant if more of them are unfit in evolutionary terms and so a higher percentage of them die before being able to reproduce, a problem that persists into subsequent generations. (It's true an older, presumably older father would have more resources to lavish on offspring, which tells you how real the phenomenon must be, if even with those advantages there are these kinds of outcomes.)

Note that we're talking here about percentages. This isn't going to impact all the children. They're talking about an increase in the percentage of children who are not fit in evolutionary terms, not that all of them are so affected. Still, of course, an increase of a certain percentage in each generation is going to have wider societal implications. Nowadays, of course, we can keep children alive and able ultimately to reproduce even if they are not optimally fit. What the consequences will be for the human race is another question altogether.

I have to say I'm surprised about the lack of knowledge concerning this phenomenon as well as the lack of knowledge of IQ and genetics as a whole.

Most de nova mutations are harmful. Doesn't everyone know that?
http://massgenomics.org/2012/08/de-novo-mutations-and-human-disease.html

We've also known for years that parental age at conception is a problem for fitness. There's a big correlation between paternal (and maternal) age at conception and the incidence of Down's Syndrome too, and autism, and a number of other disorders. This is just elementary genetics, people: with age, the cells break down more, which is why cancer is usually a disease of the elderly too.
https://www.ncbi.nlm.nih.gov/pubmed/12771769

There's a reason most sperm banks don't want any sperm from men over 35, people.

European societies didn't need geneticists to tell them this either, just like they didn't need geneticists to tell them too much inbreeding wasn't a good idea. We have lots of Italian old wives' sayings about the perils of very old men fathering children. Not in every instance, of course.

Angela
05-12-16, 21:33
I would advise certain posters to cease posting incorrect, unsourced opinions. Anyone can make a mistake or be un-informed, of course, although this is pretty basic genetics, but when it has been pointed out that the opinion is scientifically unsound, to insist on it comes perilously close to trying to deliberately distort the record.

Tomenable
05-12-16, 21:34
IQ doesn't get higher from teaching. It's innate.

It does from de novo genetic mutations, not from teaching.


What the consequences will be for the human race is another question altogether.There will be no any consequences for the human race, because there is no such thing.

There are several human races (or rather taxa, if someone doesn't like the term "race").


There's a reason most sperm banks don't want any sperm from men over 35

Yes, and this reason is saving money.

They could just screen them for potential harmful mutations instead. But this is extra cost.

It does not mean that the probability that they developed some bad mutation is high.

And as I wrote, the probability of a beneficial mutation is the same as that of a bad one.

Angela
05-12-16, 21:56
Opinions un-supported by scientific data, or, indeed, refuted by scientific data are irrelevant, and no one takes them seriously, nor should they.

I would suggest some basic reading in the intelligence quotient and its heritability, and the number and nature of de novo mutations. DE NOVO MUTATIONS ARE USUALLY HARMFUL, AND THE INCIDENCE INCREASES WITH AGE, deny it as some people would like to do for some unknown, strange reason.

Tomenable
05-12-16, 21:59
Mutations are random and have random effects, so why would they be more often harmful than beneficial.

It is like saying that you will usually get the number "one" if dice is rolled 1000 times. It makes no sense.

Angela
05-12-16, 22:25
Is there a problem with reading the links to scientific studies?

http://massgenomics.org/2012/08/de-novo-mutations-and-human-disease.html

"Many, if not most human diseases have a genetic component. Thanks to advances in next-gen sequencing, a plethora of studies in recent years have shed light on the role of germline variants in heritable diseases, and of somatic mutations in cancer. They are also beginning to unravel the role of true de novo mutations — genetic variants that arise in a child but are not present in either parent — in human disease. This was the subject of an excellent article just out in Nature Reviews Genetics. Let me give you the highlights.Most of what we know about de novo mutations in humans comes from recent whole-genome and exome sequencing studies in families:


On average, humans acquire ~74 de novo single nucleotide variants (SNVs) per genome per generation.
The rate of de novo mutations seems higher in individuals with genetic diseases, particularly sporadic disorders such as intellectual disability and autism.
Perhaps surprisingly, the de novo mutational load seems correlated with paternal (as opposed to maternal) age.
Mutations linked to sporadic disease are usually highly disruptive to gene function, often affecting important domains of developmental genes.

Diseases Linked to de novo MutationsDe novo mutations tend to be more deleterious than inherited variation because they haven’t undergone the same level of evolutionary selection. This fact, combined with the observation that they occur with some appreciable frequency, makes de novo mutation an an intriguing explanation for sporadic diseases. In support of this notion, recent family-based exome sequencing studies have implicated de novo mutations in a number of rare syndromes."

Please use google search to find the many articles on this subject if interested in the topic.

Tomenable
05-12-16, 22:51
Nothing in what you quoted implies that de novo mutations are more often deleterious than beneficial. Saying that they are "more often deleterious than inherited variation" =/= saying that more of them are deleterious than beneficial.

Nothing in what you posted proves my claim (that probability of them being harmful is the same as probability of them being beneficial) wrong. Inherited mutations are - of course - much more often beneficial than they are harmful.

But de novo mutations are not more often harmful than they are beneficial. Proportion is exactly 50:50. I mean, proportion of beneficial to harmful ones is 50:50. If we add neutral ones, then it is 90:5:5 (with 90% being neutral).


deny it as some people would like to do for some unknown, strange reason.

I plan to have a child or a few before 35 years of age, but I plan to have one or a few also after 35 years of age.

But this is not the reason why I deny it. The reason why I deny it is because it is wrong, and I am right.

LeBrok
05-12-16, 22:59
Not true.

Mutations are random which means that the chance of positive to negative will be 50 to 50.Nope, it is not an issue of something being good or bad by some universal forces. You see our DNA is very finely tuned "machine" where genes cooperate with each other. In this case any changes in this machine will be mostly negative. Imagine an old fashion watch. Open it and look at all the gears nicely working inside. Now try to do a random modification to any of these gears. Add more teeth to some gears, make square gears, o much bigger, and I assure you that the watch will stop working. Only in rare situation little modification of fine tuned watch will be positive. Like a modification making all gears physically stronger, or all proportionally bigger. Of course, if environment rewards such change.
It is a similar situation with our DNA. Most changes are distractive, varying from very destructive to mildly negative to neutral, and only microscopic amount of changes are truly positive.

Tomenable
05-12-16, 23:02
In this case any changes in this machine will be mostly negative.

This claim is unsupported by evidence. I did not find this statement in what Angela posted.

All what that paper says is that inherited mutations are less often harmful than de novo ones.

But inherited mutations are not harmful in the vast majority of all cases.

De novo mutations are still at least as often beneficial as they are harmful.

Angela quoted this fragment:


Perhaps surprisingly, the de novo mutational load seems correlated with paternal (as opposed to maternal) age.

Evolution made women fertile only until middle age, while men are fertile much longer. If de novo mutations associated with paternal age (but not maternal age) were really harmful, then it should be the other way around - men should be fertile only until middle age. For some reason evolution did not "want" older women to reproduce, but it did "want" older men to do it.

Why should I trust this paper more than I trust evolutionary evidence? Evolutionary evidence shows that women after menopause cannot naturally reproduce (so probably should not try artificial methods either), but older men still can.

LeBrok
05-12-16, 23:14
Nothing in what you quoted implies that de novo mutations are more often deleterious than beneficial. Saying that they are "more often deleterious than inherited variation" =/= saying that more of them are deleterious than beneficial.

Nothing in what you posted proves my claim (that probability of them being harmful is the same as probability of them being beneficial) wrong. Inherited mutations are - of course - much more often beneficial than they are harmful.

But de novo mutations are not more often harmful than they are beneficial. Proportion is exactly 50:50. I mean, proportion of beneficial to harmful ones is 50:50. If we add neutral ones, then it is 90:5:5 (with 90% being neutral).



I plan to have a child or a few before 35 years of age, but I plan to have one or a few also after 35 years of age.

But this is not the reason why I deny it. The reason why I deny it is because it is wrong, and I am right.Same as you were right with "population of young fathers not evolving." ;) Any explanation what happened from Lucy to Neolithic?

Tomenable
05-12-16, 23:18
Same as you were right with "population of young fathers not evolving." ;) Any explanation what happened from Lucy to Neolithic?Nope, your "guesstimates" that people in prehistory reproduced at 15 and lived 35 were wrong.

The truth is that in prehistory 50% of people died before the age of 15 (with 30% dying before the age of 5), and thus did not reproduce at all. The remaining 50% lived on average 55-60 years, and reproduced after 20-30 just like we today.

Read about age distribution of mortality rates. In the past, death was a thing that affected mostly children.

At least 1/2 of all people were never becoming adults because they were dying before turning 18.

Tomenable
05-12-16, 23:26
It is not true that before the invention of "modern medicine" people rarely lived to their 50th birthday.

Because the vast majority of people simply don't need "modern medicine" before 50. It is only after 50 years of age that people start having some health problems. However, children are also very vulnerable. And in the past children died like flies. The majority of people were dying before becoming adults. But if you were lucky to survive your 18th birthday, then you could expect living 60 years or sometimes even much longer. People in their 80s and 90s existed in prehistory. It was not so uncommon.

Children have weak immune systems. Add poor hygiene, take away antibiotics, and they die like flies.

Then throw also malnutrition into the mix, and death rates among children will increase even more.

Maciamo
05-12-16, 23:33
Higher IQ amongst children of older fathers can easily come from the fact that rather than spending time teaching sons sports, older men prefer to sit down with the children and share knowledge if not "wisdom".

Or it could simply be the result that higher IQ people study longer, dedicate more time to their career, and consequently also marry and have children later. As IQ is strongly hereditary, if most high IQ people marry late, it's only logical that high IQ children should have older parents. It's not a cause though, but an indirect side-effect of high IQ in modern society.

LeBrok
05-12-16, 23:35
IQ doesn't get higher from teaching. It's innate. Well, the base is natural, the capacity. Giving the same resources and environment people will achieve different IQ level, because of their specific DNA.

Otherwise environmental factor has dramatic impact on intelligence too. Practice language and you are going to be a better speaker. Isolate a child till age 10 from contact with people and child will never learn to speak properly. Practice any game and you will become muster of it. Likewise, practice logical thinking, problem solving, new methods, solutions, working systems, knowledge in general, increase memory and you will increase your IQ. Thanks to plasticity of your brain to rewire and its ability to learn.



Also, even if that could happen, i.e. IQ getting higher because of better teaching from older fathers, any speculative higher IQ in the children of older fathers is irrelevant if more of them are unfit in evolutionary terms and so a higher percentage of them die before being able to reproduce, a problem that persists into subsequent generations. (It's true an older, presumably older father would have more resources to lavish on offspring, which tells you how real the phenomenon must be, if even with those advantages there are these kinds of outcomes.)
I was going to say the same. So the full effect has to be even bigger, when resources are being equal for all.

LeBrok
05-12-16, 23:42
Higher IQ amongst children of older fathers can easily come from the fact that rather than spending time teaching sons sports, older men prefer to sit down with the children and share knowledge if not "wisdom". This plus a kid of a father in older age will have already many older brothers and sisters, therefore more interaction, more games, more learning of knowledge they already experienced, and more cunning to find its place in this competition for already stretched family resources.

Tomenable
05-12-16, 23:44
any speculative higher IQ in the children of older fathers is irrelevant if more of them are unfit in evolutionary terms and so a higher percentage of them die before being able to reproduce, a problem that persists into subsequent generations.

As you just noticed in that fragment quoted above:

1) Harmful "de novo" mutations are eliminated a few generations after their emergence, because their carriers die young.

2) Beneficial "de novo" mutations stay in the gene pool and proliferate.

So the long-term effect of having older fathers (and thus more of "de novo" mutations) is decisively positive. Not negative. Old fatherhood might sometimes be negative for a particular family, but not for the gene pool of a population as a whole.

This is why evolution did not restrict male reproductive capabilities with anything similar to menopause.


die before being able to reproduce, a problem that persists into subsequent generations.

If you die before being able to reproduce, then there are no any subsequent generations.

So a problem does not persist.

Maciamo
05-12-16, 23:45
On average, humans acquire ~74 de novo single nucleotide variants (SNVs) per genome per generation.
The rate of de novo mutations seems higher in individuals with genetic diseases, particularly sporadic disorders such as intellectual disability and autism.
Perhaps surprisingly, the de novo mutational load seems correlated with paternal (as opposed to maternal) age.


It's not that surprising considering that women are born with all their ova (egg cells) and do not produce new ones during their life. Therefore mutations could only be caused by toxins or stress, not simply by repeated cell divisions. In contrast, men produce new spermatozoa all the time, with a maturation cycle of 3 months. Mutations are more likely to occur in the spermatozoa of older men because sperm cells divide all the time, and with each mutation de novo mutations occur, which are passed to the next generation or sperm cells in that line. That is why male fertility decreases with age. As more and more mutations accumulate, a higher percentage of spermatozoa become misshapen and useless. Even those that do survive will usually carry more mutations in a 40 year-old individual than a 20-year old one. That's just the way it is. Nevertheless, most mutations are silent (i.e. don't change anything), while those that do cause changes in the organism can be either beneficial or deleterious. It's all a matter of luck, really.

Maciamo
05-12-16, 23:52
As you just noticed in that fragment quoted above:

1) Harmful "de novo" mutations are eliminated a few generations after their emergence, because their carriers die young.

2) Beneficial "de novo" mutations stay in the gene pool and proliferate.

So the long-term effect of having older fathers (and thus more of "de novo" mutations) is decisively positive. Not negative.

Old fatherhood might be sometimes negative for a particular family, but not for the gene pool of a population as a whole.

In the case of very deleterious mutations, the carriers may die very young indeed. Most miscarriages are caused by deleterious mutations in the foetus. At one point in development the broken genes make development impossible and the foetus self-aborts. It's much better this way actually. If only gynaecologists informed women about this, they would be less traumatised in the event of a miscarriage. They would at least understand that it is not their fault, and that there is nothing they could have done to prevent it if some genes were irredeemably broken.

Tomenable
05-12-16, 23:53
Nevertheless, most mutations are silent (i.e. don't change anything), while those that do cause changes in the organism can be either beneficial or deleterious. It's all a matter of luck, really.

Yes, that's how it is. Do you know what percent of all mutations are neutral (silent)?

LeBrok
06-12-16, 00:01
Nope, your "guesstimates" that people in prehistory reproduced at 15 and lived 35 were wrong.

The truth is that in prehistory 50% of people died before the age of 15 (with 30% dying before the age of 5), and thus did not reproduce at all. The remaining 50% lived on average 55-60 years, and reproduced after 20-30 just like we today.

Read about age distribution of mortality rates. In the past, death was a thing that affected mostly children.

At least 1/2 of all people were never becoming adults because they were dying before turning 18.
20-30 doesn't classify as older parents who we are talking about. Most kids were made by young parents regardless that some of them reached 60. If our natural procreative age starts at age 12-15, and most likely earlier in the past, it should tell you how important for survival of your kids was not to wait till old age. If you had first kids till 20 it would given you a chance to be around till your 40 to protect and feed your kids. To wait till 40 to procreate would drastically limit a chance of having kids at all (being alive), and looking after them. Most adult men died in wars, fights and hunting before reaching 40+.

Maciamo
06-12-16, 00:04
This plus a kid of a father in older age will have already many older brothers and sisters, therefore more interaction, more games, more learning of knowledge they already experienced, and more cunning to find its place in this competition for already stretched family resources.

Yet, all research to date show that the eldest child in a family typically has the highest IQ. See:

- Kristensen & Bjerkedal 2007 (http://science.sciencemag.org/content/316/5832/1717.full)
- Hotz & Pantano 2011 (http://www.oecd.org/els/50251786.pdf)
- Roher et al. 2015 (http://www.pnas.org/content/112/46/14224.abstract)

Tomenable
06-12-16, 00:05
If our natural procreative age starts at age 12-15Today it does. In the past it did not, because nutrition was poorer and living conditions were harsher.

In prehistory natural procreative age started at age maybe 15-18, certainly not 12-15 like nowadays.

Today children grow faster due to better nutrition and better living conditions.


Yet, all research to date show that the eldest child in a family typically has the highest IQ.

"Firstborn" usually has a special status and gets more attention from parents.

At least this was traditionally the case, and still is today in some societies.

LeBrok
06-12-16, 00:15
][/B]It is not true that before the invention of "modern medicine" people rarely lived to their 50th birthday.

Because the vast majority of people simply don't need "modern medicine" before 50. Don't you remember what you said just a moment ago?!!!

The truth is that in prehistory 50% of people died before the age of 15 (with 30% dying before the age of 5), and thus did not reproduce at all.
You know so many alternative Truths. By your calculations, your vast majority is 50%, lol, like your silent majority. ;)




It is only after 50 years of age that people start having some health problems. However, children are also very vulnerable. And in the past children died like flies. The majority of people were dying before becoming adults. But if you were lucky to survive your 18th birthday, then you could expect living 60 years or sometimes even much longer. 50% living to 60 in peaceful times maybe. Unless there was a war, plague or failed crops, or gangrene from accidental cuts, or Younger Dryas etc So no freakin way the rest lived 60. Maybe 20%.


Children have weak immune systems. Add poor hygiene, take away antibiotics, and they die like flies.It's because of the "neutral" mutations of yours. Some scientists say that half of unborn children are naturally aborted, because they are so mutated that they can't get even to first month of their life.

Angela
06-12-16, 00:17
Nope, it is not an issue of something being good or bad by some universal forces. You see our DNA is very finely tuned "machine" where genes cooperate with each other. In this case any changes in this machine will be mostly negative. Imagine an old fashion watch. Open it and look at all the gears nicely working inside. Now try to do a random modification to any of these gears. Add more teeth to some gears, make square gears, o much bigger, and I assure you that the watch will stop working. Only in rare situation little modification of fine tuned watch will be positive. Like a modification making all gears physically stronger, or all proportionally bigger. Of course, if environment rewards such change.
It is a similar situation with our DNA. Most changes are distractive, varying from very destructive to mildly negative to neutral, and only microscopic amount of changes are truly positive.

Very nice job of explaining the science in simple language for those of our posters who haven't kept up with the scientific literature.

Those who have already know that the science seems to show that de novo mutations in the vast majority of cases are not beneficial.

I don't know how it can get much clearer than this statement in the above cited source:
"De novo mutations tend to be more deleterious than inherited variation because they haven’t undergone the same level of evolutionary selection.

Just as a general proposition: "Beneficial mutations are rare."
http://rstb.royalsocietypublishing.org/content/365/1544/1153

"One of the earliest theoretical studies of the distribution of fitness effects was done by Motoo Kimura (https://en.wikipedia.org/wiki/Motoo_Kimura), an influential theoretical population geneticist (https://en.wikipedia.org/wiki/Geneticist). His neutral theory of molecular evolution proposes that most novel mutations will be highly deleterious, with a small fraction being neutral.[61] (https://en.wikipedia.org/wiki/Mutation#cite_note-61)[62] (https://en.wikipedia.org/wiki/Mutation#cite_note-62) Hiroshi Akashi more recently proposed a bimodal (https://en.wikipedia.org/wiki/Multimodal_distribution)model for the DFE, with modes centered around highly deleterious and neutral mutations.[63] (https://en.wikipedia.org/wiki/Mutation#cite_note-63) Both theories agree that the vast majority of novel mutations are neutral or deleterious and that advantageous mutations are rare, which has been supported by experimental results. One example is a study done on the DFE of random mutations in vesicular stomatitis virus (https://en.wikipedia.org/wiki/Vesicular_stomatitis_virus).[50] (https://en.wikipedia.org/wiki/Mutation#cite_note-Sanju.C3.A1n04-50) Out of all mutations, 39.6% were lethal, 31.2% were non-lethal deleterious, and 27.1% were neutral. Another example comes from a high throughput mutagenesis experiment with yeast.[55] (https://en.wikipedia.org/wiki/Mutation#cite_note-Hietpas11-55) In this experiment it was shown that the overall DFE is bimodal, with a cluster of neutral mutations, and a broad distribution of deleterious mutations."
https://en.wikipedia.org/wiki/Mutation#Distribution_of_fitness_effects

Now, I'm done. This is like arguing the shape of the earth with flat earthers, or evolution with Creationists.

As to IQ, the intelligence quotient is a very particular term and measuring it can only be done by means of the kind of hours long testing done one on one by educational psychologists which measure memory, speed of processing, visual-spatial ability, pattern recognition and on and on. Pen and ink mass produced tests, and even worse, tests like the SAT do indeed measure what is learned, not what one is capable of learning quickly.

That innate IQ is highly heritable, and relatively stable if the testing is of the kind I described.

Ed. You're absolutely right about the very high number of spontaneous abortions, and I'm not just talking about what are popularly called "miscarriages". Those are the situations where a woman knows she's two or three or four months pregnant and the fetus aborts or dies in utero and has to be removed, which is even more of a horror.

The fact is that often, when a woman is "late" or "skips" a period, she is often pregnant, but the fetus aborts because of mutational abnormalities.

Also, some people seem to be unaware of the number of children today born with less serious mutational abnormalities, or what are sometimes called birth defects. Parents just get their child the proper medical care. In prior eras, these children were still born or died shortly after birth.

Tomenable
06-12-16, 00:29
I don't know how it can get much clearer than this statement in the above cited source: "De novo mutations tend to be more deleterious than inherited variation because they haven’t undergone the same level of evolutionary selection.

You underlined with bold font a wrong part of that quote.

It says: "tend to be more deleterious than inherited variation".

It does not say, that over 50% of de novo mutations are deleterious.


because they haven’t undergone the same level of evolutionary selection.

De novo mutations have not undergone any evolutionary selection at all.

Because they have just emerged, so how could they be undergo any selection?

However, they will be subjected to evolutionary selection in next generations.


Just as a general proposition: "Beneficial mutations are rare."

As are deleterious mutations. The vast majority are silent (or neutral as I called it).

LeBrok
06-12-16, 00:29
Today it does. In the past it did not, because nutrition was poorer and living conditions were harsher.

In prehistory natural procreative age started at age maybe 15-18, certainly not 12-15 like nowadays.

Today children grow faster due to better nutrition and better living conditions.No reason to speculate. Check puberty age for today's hunter gatherers. There are still secluded groups in jungles and I'm sure their is some research on it. I bet you, it will be around 12 years old.




"Firstborn" usually has a special status and gets more attention from parents. Attention yes, but the last one grows up in better material conditions.

Tomenable
06-12-16, 00:37
As to IQ, the intelligence quotient is a very particular term and measuring it can only be done by means of the kind of hours long testing done one on one by educational psychologists which measure memory, speed of processing, visual-spatial ability, pattern recognition and on and on.

In fact it is enough to take a look at the Bell Curve in your "Educational Attainment" Report in DNA Land:

https://dna.land

It is called "Educational Attainment" but what it really measures are alleles associated (correlated) with IQ.

This report shows 30 SNPs and "effect sizes" which are either positive or negative.

"De novo mutations" can also occur in genes which affect these "effect sizes".

Angela
06-12-16, 00:44
"One of the earliest theoretical studies of the distribution of fitness effects was done by Motoo Kimura (https://en.wikipedia.org/wiki/Motoo_Kimura), an influential theoretical population geneticist (https://en.wikipedia.org/wiki/Geneticist). His neutral theory of molecular evolution proposes that most novel mutations will be highly deleterious, with a small fraction being neutral.[61] (https://en.wikipedia.org/wiki/Mutation#cite_note-61)[62] (https://en.wikipedia.org/wiki/Mutation#cite_note-62) Hiroshi Akashi more recently proposed a bimodal (https://en.wikipedia.org/wiki/Multimodal_distribution)model for the DFE, with modes centered around highly deleterious and neutral mutations.[63] (https://en.wikipedia.org/wiki/Mutation#cite_note-63) Both theories agree that ...advantageous mutations are rare, which has been supported by experimental results."

Is it clear now or do I also have to explain that MOST means OVER 50%?

For everyone's information, IQ, like most human traits, is polygenic, affected by perhaps hundreds if not thousands of alleles. No scientist claims to know what they all are, and therefore no retail testing company is going to be able to tell you if you're "genetically" smarter than anyone else. This is voodoo genetics and part of why there is a blowback against amateurs being left to interpret data from retail genetics companies.

Tomenable
06-12-16, 00:47
Check puberty age for today's hunter gatherers.Today's hunter-gatherers are not European, not even Caucasoid. And average puberty age varies between the races. For example for African-American girls, average age at menarche is below 12 and for European-American girls it is over 13.

For East Asian girls, average age at menarche is even older than for European girls.

The possible correlation with IQ (higher average IQ = later menarche) is interesting.

Also twinning rates are different between the races. For example East Asians have twins on average 4 times per 1000 pregnancies. Europeans - 8 times per 1000 pregnancies. Sub-Saharan Africans - over 16 times per 1000 pregnancies.

Triplets per million pregnancies are: 10 for Asians, 100 for Europeans, 1700 for Sub-Saharan Africans.


"One of the earliest theoretical studies of the distribution of fitness effects was done by Motoo Kimura, an influential theoretical population geneticist. His neutral theory of molecular evolution proposes that most novel mutations will be highly deleterious, with a small fraction being neutral.[61][62] Hiroshi Akashi more recently proposed a bimodal model for the DFE, with modes centered around highly deleterious and neutral mutations.[63] Both theories agree that ... advantageous mutations are rare, which has been supported by experimental results."

These are so far just theories, not proven facts. And as we already agreed, highly deleterious mutations eliminate themselves from gene pool (because carriers of these mutations do not live long enough to reproduce).

Angela
06-12-16, 01:01
You know, you can post all the studies in the world, but if people don't read them, or skip over pertinent phrases, or refuse to accept them for whatever bizarre reason, there's really not much to be done except to ignore such comments.

""One of the earliest theoretical studies of the distribution of fitness effects was done by Motoo Kimura, an influential theoretical population geneticist. His neutral theory of molecular evolution proposes that most novel mutations will be highly deleterious, with a small fraction being neutral.[61][62] Hiroshi Akashi more recently proposed a bimodal model for the DFE, with modes centered around highly deleterious and neutral mutations.[63] Boththeories agree that ... advantageous mutations are rare, which has been supported by experimental results."?

Also, please go back to my original link, where it says in black and white that whole genome sequencing has indeed shown that most denovo mutations are deleterious, whether strongly or weakly.

Tomenable
06-12-16, 01:02
Well - I don't deny that advantageous mutations are rare.

I claim that both advantageous and deleterious are rare.

LeBrok
06-12-16, 01:03
Today's hunter-gatherers are not European, not even Caucasoid. And average puberty age varies between the races. For example for African-American girls, average age at menarche is below 12 and for European-American girls it is over 13.

For East Asian girls, average age at menarche is even older than for European girls.Yah, yah, the point was that most majority of people in the past was born and survived to young parents till 30, period. If you have undisclosed information which points to the fact that only human evolutionary changes are due to older fathers, now is the time to speak.

Tomenable
06-12-16, 01:08
For everyone's information, IQ, like most human traits, is polygenic, affected by perhaps hundreds if not thousands of alleles. No scientist claims to know what they all are, and therefore no retail testing company is going to be able to tell you if you're "genetically" smarter than anyone else. This is voodoo genetics and part of why there is a blowback against amateurs being left to interpret data from retail genetics companies.

Comparing IQ test results with DNA Land "Educational Attainment" results shows that there is a correlation between them.


No scientist claims to know what they all are

Not all, but a large part is already known. There are also studies about frequencies of IQ associated alleles in populations.

LeBrok
06-12-16, 01:16
Well - I don't deny that advantageous mutations are rare.

I claim that both advantageous and deleterious are rare.
Take cigarette smokers for example, and smoke effect on mutations in lung DNA, causing cancer. If your claim that destructive and beneficial mutations are equal in benefits to the human life, mostly neutral, why is that we can see that most long time smokers die of lung cancer. As we know lung cancer is caused by damage/mutation in DNA structure. Why we don't see the good mutations counteracting the bad mutations? Why don't we see many smokers getting better lungs, very healthy lungs and better than average, after long time smoking? On contrary, we see damage, destruction and death from mutations. Where are the good mutations counterbalancing the bad ones?

Look at as getting older and older. Most aging is caused of destruction to our DNA, slowly being damage/mutating, therefore functions worse and worse, slower and slower, with every year till we die. Life long sequence of deleterious mutations kills us.

Tomenable
06-12-16, 01:21
Take cigarette smokers for example, and smoke effect on mutations in lung DNA, causing cancer. If your claim that destructive and beneficial mutations are equal in benefits to the human life, mostly neutral, why is that we can see that most long time smokers die of lung cancer. As we know lung cancer is caused by damage/mutation in DNA structure. Why we don't see the good mutations counteracting the bad mutations? Why don't we see many smokers getting better lungs, very healthy lungs and better than average, after long time smoking? On contrary, we see damage, destruction and death from mutations. Where are the good mutations counterbalancing the bad ones?

Good question.

For example Jeanne Calment smoked cigarettes from the age of 21 (1896) to the age of 117 (1992).

And she did not die (in 1997) from lung cancer, but from something else.

That said, for the majority of people smoking is indeed harmful. As is nuclear radiation for example.

But why should we compare a natural process like aging, with smoking?

Angela
06-12-16, 01:25
Let's see, do I believe the many papers written on this subject by reputable scientists or Joe Blow on the internet?

All other things being equal, the odds are that you'll have healthier children with a man under 35 than with a man 40+, no matter how much money he has. Those sperm just deteriorate with time. Ladies, take note. With women, by the time her eggs have deteriorated she can't have children anymore anyway, thank-goodness.

Also, whoever said that all deleterious mutations are immediately lethal? We know that most of them aren't immediately lethal, given that the papers above say most people have about 70 denovo mutations, and most of us are here without massive medical interventions.

However, if you have enough even mildly deleterious mutations flooding into the societal gene pool because a good number of powerful old men are hogging all the nubile young women, and then the children of those unions are allowed to reach reproductive age because of the father's power and the advantages he can provide, the effect on society isn't very good. Add to that the fact that in societies with this kind of elite superstructure you have a lot of intermarriage an inbreeding, it's not a good situation.

It was a byword in Europe that the children of the aristocracy were more "delicate". Well, now we know some of the reasons why. No wonder some of these aristocratic trees show evidence of some hanky-panky. Some of these old ***** either couldn't procreate at all, or the children were sickly, and in a pre-modern society, died. If your status depends on providing a healthy male heir, I can see why some women turned elsewhere.

LeBrok
06-12-16, 01:25
Good question.

For example Jeanne Calment smoked cigarettes from the age of 21 (1896) to the age of 117 (1992).

And still, she did not die (in 1997) of lung cancer, but of something else.

That said, for the majority of people smoking is indeed harmful. As is nuclear radiation for example.

But why should we compare a natural process like aging, with smoking? Because it all environmental damage to our DNA. Every mutation comes from environmental effects. Cosmic radiation, radon gas, free radicals, malnutrition, etc. Most of our aging is caused by environmental damage to DNA structure.

Tomenable
06-12-16, 01:32
All other things being equal, the odds are that you'll have healthier children with a man under 35 than with a man 40+

And what about women?

Is the likelihood of my children being healthy with a woman of 40 the same as with a woman of 25?

Is the de novo mutational load correlated only with paternal age, and not at all with maternal age?

The only genetic difference between men and women is XY vs. XX so is it related to Y chromosome?

If so, then maybe men with some Y-DNA haplogroups have a lower risk of deleterious mutations?

Tomenable
06-12-16, 01:36
With women, by the time her eggs have deteriorated she can't have children anymore anyway, thank-goodness.

Most of women can have children until around 50. But you just claimed that sperm deteriorates already by 35.

So why is there a 15 years difference?

Angela
06-12-16, 01:39
Because it all environmental damage to our DNA. Every mutation comes from environmental effects. Cosmic radiation, radon gas, free radicals, malnutrition, etc. Most of our aging is caused by environmental damage to DNA structure.

I once asked an oncologist this question about why some people can smoke for decades before getting cancer if they get it at all while some people are dead at forty. He said it depends how many protective snps were part of their genetic code and whether or not and how early there was damage to those protective snps.

So, for me the moral of the story is just don't do it at all no matter what.

There's something similar for bladder cancer in men. There's a link between the combination of smoking and drinking and bladder cancer.

Another killer is exposure to asbestos. There's lots of litigation seeking damages for people who developed cancer after working with roofing materials, insulation, etc.

LeBrok
06-12-16, 01:41
Good question.

For example Jeanne Calment smoked cigarettes from the age of 21 (1896) to the age of 117 (1992).

And she did not die (in 1997) from lung cancer, but from something else.

That said, for the majority of people smoking is indeed harmful. As is nuclear radiation for example.

But why should we compare a natural process like aging, with smoking?Because she never had cancer causing mutation, or her DNA repair system was very superior. Mind, that there is not even one study discovering good lung mutations in smokers and their lungs functioning better than before smoking.
We should also add viruses as cause of many deleterious mutations in humans, damage to DNA, during our lifetime.

Tomenable
06-12-16, 01:42
Another killer is exposure to asbestos. There's lots of litigation seeking damages for people who developed cancer after working with roofing materials, insulation, etc.

Yes. And most of these plaintiffs are men. Because, sadly, there is no gender parity of 50:50 in asbestos-related jobs. Women are so discriminated against. And a woman working at a nursery even gets paid less (!) than a man working with asbestos.

Can you imagine? What a gross injustice.


So, for me the moral of the story is just don't do it at all no matter what.

The only thing I ever smoked was a Shisha Pipe when I was on a trip to Tunisia.

MarkoZ
06-12-16, 01:48
Comparison of IQ scores of persons from across the autism spectrum and unaffected people and their relation to mutational load:


We examined the incidence and targets of DN LGD mutations for children with lower and higher IQs. Affected children with higher IQs have a greater incidence of LGD mutations than unaffected siblings, but a lower incidence than affected females or males with lower IQ. Moreover, there are few recurrently hit genes among the DN LGD targets of affected males with higher IQ, and little overlap with the DN LGD targets of affected males with lower IQ or females. LGD targets in higher IQ males are not enriched for the FMRP-associated genes. These observations suggest a different distribution of genetic mechanisms causing ASD in higher IQ males.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4611648/

So it seems like high IQ individuals do tend to have more de novo mutations than people of average intelligence, but less than individuals with significantly lower IQ scores. An interesting case of this dynamic would be the Ashkenazic Jews, who have a disproportionate number of brilliant individuals among them but also a comparatively high incidence of mental retardation.

Tomenable
06-12-16, 01:52
I once asked an oncologist this question about why some people can smoke for decades before getting cancer if they get it at all while some people are dead at forty. He said it depends how many protective snps were part of their genetic code and whether or not and how early there was damage to those protective snps.

^ Probably these "bonfire adaptation" SNPs that we inherited from the Neanderthals.

For example rs901033.

So in the end we got something useful from them! Interracial intermarriage isn't so bad.

LeBrok
06-12-16, 01:57
Comparison of IQ scores of persons from across the autism spectrum and unaffected people and their relation to mutational load:

[/FONT][/COLOR]
MarkoZ, please add source or name of author to your quote unless it was your creation.

Angela
06-12-16, 01:59
What on earth are you talking about? Litigators are the lawyers. Nowadays there's still a bit of a skew toward men, but there's a lot of women litigators, I assure you. The people affected are the plaintiffs.

You might want to consider that nowadays more women smoke than men, just as many female children as male children sit in asbestos insulated classrooms, just as many women as men are exposed to radiation, electro-magnetic fields, impure water, and on and on. So far as I know men don't get breast cancer at the level of women, or ovarian cancer at all either.

You know what, no, I'm not going to continue with this.

I find any "competition" as to who suffers the most incidences of cancer because of exposure to environmental toxins, men or women, disgusting, frankly.

People suffering is people suffering. That's all I see, not their gender, or their race or ethnic group, for that matter.

I'm out. This is becoming pointless. Some people don't know when they've lost or how to withdraw graciously.

Tomenable
06-12-16, 02:03
So far as I know men don't get breast cancer at the level of women, or ovarian cancer at all either.


https://www.youtube.com/watch?v=nQcgD5DpVlQ

Tomenable
06-12-16, 02:17
So it seems like high IQ individuals do tend to have more de novo mutations than people of average intelligence

So I have good news (yay!) for you - de novo mutations are on the decline, "fitness" is increasing: :grin:

http://bioinfo.ut.ee/web/wp-content/uploads/2013/05/jc_lauris_2013a.pdf

https://www.gwern.net/docs/algernon/2012-woodley.pdf

Smash the patriarchy!:

http://s11.postimg.org/w61blmlub/Innovation_IQ.png


However, if you have enough even mildly deleterious mutations flooding into the societal gene pool because a good number of powerful old men are hogging all the nubile young women, and then the children of those unions are allowed to reach reproductive age because of the father's power and the advantages he can provide, the effect on society isn't very good. Add to that the fact that in societies with this kind of elite superstructure you have a lot of intermarriage an inbreeding, it's not a good situation.

It was a byword in Europe that the children of the aristocracy were more "delicate". Well, now we know some of the reasons why. No wonder some of these aristocratic trees show evidence of some hanky-panky. Some of these old ***** either couldn't procreate at all, or the children were sickly, and in a pre-modern society, died. If your status depends on providing a healthy male heir, I can see why some women turned elsewhere.

So you should tell these old fart American cis white R1b patriarchs to stop searching for nubile young women in Eastern Europe. We don't want your horse-riding Bell-Beaker patriarchs with Gedrosian (or was that Geriatric?) admixture here:

https://media.giphy.com/media/ixLoZvfG8vtNC/giphy.gif

davef
06-12-16, 09:54
Not placing any blame on whoever put this article up; just that as a child born to a 38 year old father and 30 year old mother, reading this article has made me very very anxious.

I was hyperactive as a kid and teen, but with meds my grades and number of intellectual achievements skyrocketed. I'm also very healthy physically. I wonder if my hyperactivity was caused by a mutation due to advanced paternal age.

I bragged a bit, but I wanted to show that I turned out great in spite of my dad being 38 when I was born.

Hopefully I'm not destined for a screwy future down the road as a result of the advanced paternal age at birth.

Maciamo
06-12-16, 11:07
"One of the earliest theoretical studies of the distribution of fitness effects was done by Motoo Kimura (https://en.wikipedia.org/wiki/Motoo_Kimura), an influential theoretical population geneticist (https://en.wikipedia.org/wiki/Geneticist). His neutral theory of molecular evolution proposes that most novel mutations will be highly deleterious, with a small fraction being neutral.[61] (https://en.wikipedia.org/wiki/Mutation#cite_note-61)[62] (https://en.wikipedia.org/wiki/Mutation#cite_note-62) Hiroshi Akashi more recently proposed a bimodal (https://en.wikipedia.org/wiki/Multimodal_distribution)model for the DFE, with modes centered around highly deleterious and neutral mutations.[63] (https://en.wikipedia.org/wiki/Mutation#cite_note-63) Both theories agree that ...advantageous mutations are rare, which has been supported by experimental results."

Is it clear now or do I also have to explain that MOST means OVER 50%?

Sorry, but it is simply not possible than over 50% of de novo mutations are highly deleterious. As you mentioned above, on average, humans acquire ~74 de novo single nucleotide variants (SNVs) per genome per generation. That would mean that every individual has over 37 highly deleterious mutations, in addition to those inherited from each parent. To keep it simple, let's say even 35 highly deleterious mutations, which would be an underestimation (under 50%) according to what Kimura-san claims. A person would therefore be born with 35 de novo highly deleterious mutations but inherited about 35 highly deleterious mutations from his/her parents (half of each parent's 35 mutations but x2 as they are 2 parents). By that logic, each generation would ineluctably add 35 highly deleterious mutations to the germ line. It quickly rises to the thousands of highly deleterious mutations per individual. Mildly deleterious mutation can cause poor vision, allergies, low intelligence, frequent colds, and so on. Highly deleterious mutations are things that can cause foetuses to self-abort to people to be born with severe genetic conditions like cystic fibrosis or Huntington's disease, which lead to deaths at a relatively young age. It just doesn't make any sense to say that all people are born with thousands of highly deleterious mutations, including at least 35 de novo ones. That would be the end of the species.

Anyway, anyone who has studied biology should know that statistically most mutations are synonymous because of the high redundancy in the way amino acids are encoded by DNA (or actually RNA during translation (https://en.wikipedia.org/wiki/Translation_(biology))). To illustrate for non biologists, here is a table of RNA translation to amino acids. This is the way our genome encodes proteins. Each amino acid is encoded by a three genetic bases (A, C, G or T in DNA, which become U, G, C or A after transcription (https://en.wikipedia.org/wiki/Transcription_(biology)) to RNA). For example, if you want to produce Methionine, the amino acid that signal the beginning any protein sequence, you will need the RNA sequence AUG. If a mutation occurs in any of these three 'letters', it won't produce Methionine by another amino acid (e.g. Isoleucine if the final G becomes an A), and the protein won't be made. This would be an example of deleterious mutation, as the body cannot produce one type of protein. In most cases this is bad enough to guarantee the non-viability of the foetus.

However, as you can see on the table below, other amino acids can be encoded by any of 2, 3, 4 or even 6 different sequences in the case of Leucine. So if a mutation occurs in a CUA sequence for Leucine, chances are that the resulting protein will still be Leucine. Change the C into a U or an A and you still get Leucine. Change the final A into a C, G or U, and you still get Leucine. A mutation in the central U would result in a different amino acid. But even so, a mutation from U to C would give Proline, which is another hydrophobic amino acid with similar properties that is unlikely to cause major disruptions to the protein structure. So the only cases in which a mutation would be highly deleterious here is if the CUA sequences becomes CCA (Glycine) or CGA (Arginine), as they would turn a hydrophobic amino acid into a hydrophilic or a positively charged one. In this case, out of 9 possible mutations (3 for each letter), 7 are neutral and only 2 are deleterious. Considering that amino acids with similar properties (e.g. hydrophobic) have similar sequences, the chances of mutations changing those properties are not that high.

http://cbm.msoe.edu/scienceOlympiad/module2012/assets/dnaSequencingStructure6.jpg


Any change that tempers with an initial Methionine or results in a stop codon (UAA, UGA or UAG) would be particularly deleterious. You can see here a few examples of highly deleterious mutations.

https://upload.wikimedia.org/wikipedia/commons/7/72/Notable_mutations.svg

I haven't calculated all the possibilities of mutations for each amino acid, nor applied those results to the percentage of each sequence present in the human genome. That is the kind of humongous calculation that should be left to computers. But at first sight it looks like over half of mutations would be silent. More than mutations, it is deletions and insertions that tend to cause major problems, as they cause frameshift mutations (https://en.wikipedia.org/wiki/Frameshift_mutation), potentially altering whole genes.

Furthermore, proteins are only encoded by our exome (coding DNA), which represents a mere 1% of the total genome. Any mutation that occurs in the 99% of non-coding DNA would in all likelihood have no effect whatsoever on fitness or phenotype. That is what we observe in Y-DNA mutations. Over 15,000 Y-DNA mutations have been identified at present, but only a tiny minority (http://www.eupedia.com/forum/threads/29116-Influence-of-Y-chromosomal-DNA-mutations-on-behaviour-and-reproductory-success) of them seem to have been selected by evolution because they benefited the carriers.

Maciamo
06-12-16, 14:10
Not placing any blame on whoever put this article up; just that as a child born to a 38 year old father and 30 year old mother, reading this article has made me very very anxious.

I was hyperactive as a kid and teen, but with meds my grades and number of intellectual achievements skyrocketed. I'm also very healthy physically. I wonder if my hyperactivity was caused by a mutation due to advanced paternal age.

I bragged a bit, but I wanted to show that I turned out great in spite of my dad being 38 when I was born.

Hopefully I'm not destined for a screwy future down the road as a result of the advanced paternal age at birth.


I wouldn't worry too much about your parents' age at the time of your conception. The average mother's age at the time of their first child's birth ranges between 28 and 30 years old in most developed countries - the highest being Australia, the UK and Switzerland. In families that have 3 or 4 kids (more is becoming rare) the last child would be born when the mother is about 36 years old. For fathers, add 2 or 3 years in average. So most children born in developed countries today have parents aged between 28 and 40 years old, and the average is actually a bit higher among higher social classes.

Rupert Murdoch (https://en.wikipedia.org/wiki/Rupert_Murdoch)'s last two children were born when he was 70 and 72 years old. That would be more worrying.

Maciamo
06-12-16, 14:18
It was a byword in Europe that the children of the aristocracy were more "delicate". Well, now we know some of the reasons why. No wonder some of these aristocratic trees show evidence of some hanky-panky. Some of these old ***** either couldn't procreate at all, or the children were sickly, and in a pre-modern society, died. If your status depends on providing a healthy male heir, I can see why some women turned elsewhere.

There must be other reasons since traditionally aristocrats started having children at a younger age than peasants, at least in Britain where this is well documented. Matt Ridley explained in his book The Red Queen (https://www.amazon.co.uk/Red-Queen-Evolution-Penguin-Science/dp/0140167722) that medieval peasant men really lucky to marry before middle age, as they didn't have enough money to support a family before that. Rich people in contrast started having children from their late teens (for girls) to early twenties (for men) because they could afford it and their families were often anxious to produce heirs quickly.

Angela
06-12-16, 16:53
Sorry, but it is simply not possible than over 50% of de novo mutations are highly deleterious. As you mentioned above, on average, humans acquire ~74 de novo single nucleotide variants (SNVs) per genome per generation. That would mean that every individual has over 37 highly deleterious mutations, in addition to those inherited from each parent. To keep it simple, let's say even 35 highly deleterious mutations, which would be an underestimation (under 50%) according to what Kimura-san claims. A person would therefore be born with 35 de novo highly deleterious mutations but inherited about 35 highly deleterious mutations from his/her parents (half of each parent's 35 mutations but x2 as they are 2 parents). By that logic, each generation would ineluctably add 35 highly deleterious mutations to the germ line. It quickly rises to the thousands of highly deleterious mutations per individual. Mildly deleterious mutation can cause poor vision, allergies, low intelligence, frequent colds, and so on. Highly deleterious mutations are things that can cause foetuses to self-abort to people to be born with severe genetic conditions like cystic fibrosis or Huntington's disease, which lead to deaths at a relatively young age. It just doesn't make any sense to say that all people are born with thousands of highly deleterious mutations, including at least 35 de novo ones. That would be the end of the species.

Anyway, anyone who has studied biology should know that statistically most mutations are synonymous because of the high redundancy in the way amino acids are encoded by DNA (or actually RNA during translation (https://en.wikipedia.org/wiki/Translation_(biology))). To illustrate for non biologists, here is a table of RNA translation to amino acids. This is the way our genome encodes proteins. Each amino acid is encoded by a three genetic bases (A, C, G or T in DNA, which become U, G, C or A after transcription (https://en.wikipedia.org/wiki/Transcription_(biology)) to RNA). For example, if you want to produce Methionine, the amino acid that signal the beginning any protein sequence, you will need the RNA sequence AUG. If a mutation occurs in any of these three 'letters', it won't produce Methionine by another amino acid (e.g. Isoleucine if the final G becomes an A), and the protein won't be made. This would be an example of deleterious mutation, as the body cannot produce one type of protein. In most cases this is bad enough to guarantee the non-viability of the foetus.

However, as you can see on the table below, other amino acids can be encoded by any of 2, 3, 4 or even 6 different sequences in the case of Leucine. So if a mutation occurs in a CUA sequence for Leucine, chances are that the resulting protein will still be Leucine. Change the C into a U or an A and you still get Leucine. Change the final A into a C, G or U, and you still get Leucine. A mutation in the central U would result in a different amino acid. But even so, a mutation from U to C would give Proline, which is another hydrophobic amino acid with similar properties that is unlikely to cause major disruptions to the protein structure. So the only cases in which a mutation would be highly deleterious here is if the CUA sequences becomes CCA (Glycine) or CGA (Arginine), as they would turn a hydrophobic amino acid into a hydrophilic or a positively charged one. In this case, out of 9 possible mutations (3 for each letter), 7 are neutral and only 2 are deleterious. Considering that amino acids with similar properties (e.g. hydrophobic) have similar sequences, the chances of mutations changing those properties are not that high.

http://cbm.msoe.edu/scienceOlympiad/module2012/assets/dnaSequencingStructure6.jpg


Any change that tempers with an initial Methionine or results in a stop codon (UAA, UGA or UAG) would be particularly deleterious. You can see here a few examples of highly deleterious mutations.

https://upload.wikimedia.org/wikipedia/commons/7/72/Notable_mutations.svg

I haven't calculated all the possibilities of mutations for each amino acid, nor applied those results to the percentage of each sequence present in the human genome. That is the kind of humongous calculation that should be left to computers. But at first sight it looks like over half of mutations would be silent. More than mutations, it is deletions and insertions that tend to cause major problems, as they cause frameshift mutations (https://en.wikipedia.org/wiki/Frameshift_mutation), potentially altering whole genes.

Furthermore, proteins are only encoded by our exome (coding DNA), which represents a mere 1% of the total genome. Any mutation that occurs in the 99% of non-coding DNA would in all likelihood have no effect whatsoever on fitness or phenotype. That is what we observe in Y-DNA mutations. Over 15,000 Y-DNA mutations have been identified at present, but only a tiny minority (http://www.eupedia.com/forum/threads/29116-Influence-of-Y-chromosomal-DNA-mutations-on-behaviour-and-reproductory-success) of them seem to have been selected by evolution because they benefited the carriers.

According to the papers I've read, including the ones to which I linked above, the average number of de novo mutations per person is about 71, certainly not thousands or even hundreds. Also, the papers seem to include deletions and insertions within the broad category of mutations. Nor, as I mentioned above, are most "mutations" immediately lethal. In fact, most are mildly deleterious.

To say that beneficial mutations are rare is not to say that they aren't important to evolution. Lactase persistence is a prime example. Also, beneficial or deleterious is determined in evolutionary terms by the environment. The question is, are the changes deleterious or beneficial in terms of fitness for the environment.

You might want to take a look at some of the newer papers using whole genomes that deal not just in theory but in the actual determination of how many de novo "changes" are beneficial versus deleterious.

As to the breeding patterns of the aristocracy and royalty, I agree that old and powerful rulers having access to a lot of women (obviously not just their wives, but also their mistresses, official and otherwise) is only one factor affecting the "fitness" of their children. Even in terms of that one factor, yes, someone entering the guild would not be able to marry young. Would that apply to serfs living on the manor, or was it like the situation on slave plantations, where more children equaled more farm hands? Of course, other factors were also involved. Breeding too young is just as problematical, especially for women. There's also the fact that they were all too inbred. It was a veritable perfect storm for eventual unfitness.

Maciamo
06-12-16, 17:04
According to the papers I've read, including the ones to which I linked above, the average number of de novo mutations per person is about 71, certainly not thousands or even hundreds. Also, the papers seem to include deletions and insertions within the broad category of mutations. Nor, as I mentioned above, are most "mutations" immediately lethal. In fact, most are mildly deleterious.

I was explaining that these mutations accumulate from generation to generation. With 70 new mutations at each generation, the total quickly reaches the thousands. If most (over 50%) are highly deleterious as you wrote, then that is still thousands of deleterious mutations in all of us only since the Middle Ages, and tens of thousands since the end of the last Ice Age.


You might want to take a look at some of the newer papers using whole genomes that deal not just in theory but in the actual determination of how many de novo "changes" are beneficial versus deleterious.

Such as? The studies by Kimura and Akashi that you mentioned above were both theoretical models.

Angela
06-12-16, 17:38
I was explaining that these mutations accumulate from generation to generation. With 70 new mutations at each generation, the total quickly reaches the thousands. If most (over 50%) are highly deleterious as you wrote, then that is still thousands of deleterious mutations in all of us only since the Middle Ages, and tens of thousands since the end of the last Ice Age.



Such as? The studies by Kimura and Akashi that you mentioned above were both theoretical models.

That specific point was based on a quote from Kimura about his theory. The remainder of the quote is referring to another theory from Akashi where the majority are either "effectively neutral" or highly deleterious. There is then a discussion of actual findings. This is the following section:

" Both theories agree that the vast majority of novel mutations are neutral or deleterious and that advantageous mutations are rare, which has been supported by experimental results. One example is a study done on the DFE of random mutations in vesicular stomatitis virus (https://en.wikipedia.org/wiki/Vesicular_stomatitis_virus).[50] (https://en.wikipedia.org/wiki/Mutation#cite_note-Sanju.C3.A1n04-50) Out of all mutations, 39.6% were lethal, 31.2% were non-lethal deleterious, and 27.1% were neutral. Another example comes from a high throughput mutagenesis experiment with yeast.[55] (https://en.wikipedia.org/wiki/Mutation#cite_note-Hietpas11-55) "

I particularly like the paper where this is found because besides giving an overview of the entire topic, it cites dozens of papers on all aspects of this topic.

http://rstb.royalsocietypublishing.org/content/365/1544/1153

One of the first links I provided discusses the whole genome sequencing, but addressed only some of the denovo deleterious "mutations" they found.

See:
http://massgenomics.org/2012/08/de-novo-mutations-and-human-disease.html

Tomenable
27-12-16, 12:50
To say that beneficial mutations are rare is not to say that they aren't important to evolution. Lactase persistence is a prime example.

There are probably thousands of de novo mutations even more beneficial than lactase persistence, which have aroused recently, after the "out of Africa" migration, but it is politically incorrect to talk about them, as it might imply inequality between the races. What is especially inconvenient for people who claim that differences in outcomes between the races are caused entirely by non-genetic factors (such as "microagressions" or "institutional racism"), and who claim that evolutionary adaptation has spared the brain, is the fact that European hunters apparently developed a relatively high number of de novo mutations when compared with other populations. This was mentioned e.g. by Key et al. 2016 (quote: "Adaptive alleles - especially those associated with pigmentation - are mostly of hunter-gatherer origin"; link: http://www.nature.com/ncomms/2016/160318/ncomms10775/full/ncomms10775.html).

For some people it would be more convenient and more PC to assume that evolution stopped 100,000 ybp.

Tomenable
27-12-16, 13:10
I'm not saying that racism doesn't exist and that it is not a problem that should be dealt with.

But I think that there is a lot more of racism outside of the Western World than within it. You just don't hear about this on the media (and I guess it has something to do with propaganda according to which only White people can be racist).

For example in Bolivia Spanish-speaking Mestizos who are around 80-85% genetically Amerindian (local Bolivian average) are very racist against Quechua-speakers, who are only slightly more genetically Amerindian (90-95% on average).

This just shows how ridiculous are claims by some people, that multiculturalism and increased race-mixing can help to end racism. Prevalence of race mixing has nothing to do with racism, and Latin America - one of the most racist parts of the world today - is the best example of this. Ironically in many Hispanic countries mixed-race people are the most racist ones.

This video of "microaggresions" (?) by Mestizos against Amerinds in Bolivia is very disturbing:

https://www.youtube.com/watch?v=gimwICxs_dA


https://www.youtube.com/watch?v=gimwICxs_dA

Tomenable
27-12-16, 13:19
More: https://www.youtube.com/watch?v=2Wj6yez66ws


https://www.youtube.com/watch?v=2Wj6yez66ws

And pretty much everyone in Bolivia is of the same race.

Bolivian reference populations in GEDmatch calculators:

1) HarappaWorld:

Bolivian - 90,5% Amerindian, 9% European, 0,5% African

2) MDLP K23b:

Quechua Bolivia - 99% Amerindian, 1% European, 0% African
Bolivian La Paz - 98% Amerindian, 2% European, 0% African
Bolivian Cochabamba - 93% Amerindian, 7% European, 0% African
Bolivian Pando - 91% Amerindian, 8,5% European, 0,5% African
Bolivian - 88% Amerindian, 12% European, 0% African

3) puntDNAL K10:

Bolivian1 - 97% Amerindian, 3% European, 0% African
Bolivian2 - 85% Amerindian 14% European, 1% African

Bolivian1 is probably Western Bolivian and Bolivian2 is Eastern Bolivian.

===============

People who are genetically over 50% European are practically non-existent in Bolivia.

Yet they discriminate against these who have few percent more of Amerind ancestry.

Angela
27-12-16, 16:37
There are things that are much worse than political correctness, and one of them is the deliberate distortion of scientific facts in the service of racism.

To repeat:

" Both theories agree that the VAST MAJORITY of novel mutations are neutral or deleterious and that advantageous mutations are rare, which has been supported by experimental results. "

Anyone with any knowledge of evolution knows that it has continued in every part of the world. No human beings are clones of our African ancestors of 100,000 years ago.

I won't be debating this issue any further. It's settled science.

LeBrok
27-12-16, 20:00
I'm not saying that racism doesn't exist and that it is not a problem that should be dealt with.

But I think that there is a lot more of racism outside of the Western World than within it. You just don't hear about this on the media (and I guess it has something to do with propaganda according to which only White people can be racist).

For example in Bolivia Spanish-speaking Mestizos who are around 80-85% genetically Amerindian (local Bolivian average) are very racist against Quechua-speakers, who are only slightly more genetically Amerindian (90-95% on average).

This just shows how ridiculous are claims by some people, that multiculturalism and increased race-mixing can help to end racism. Prevalence of race mixing has nothing to do with racism, and Latin America - one of the most racist parts of the world today - is the best example of this. Ironically in many Hispanic countries mixed-race people are the most racist ones.

This video of "microaggresions" (?) by Mestizos against Amerinds in Bolivia is very disturbing:

https://www.youtube.com/watch?v=gimwICxs_dA
Pointing to others being reacists, or bigger racists, won't stop you being one. If you can't deal with this issue by yourself perhaps visit psychologist. And stop using every thread as an occasion to show us "how you are not a racist".

Tomenable
27-12-16, 20:24
"Racism blah, blah!"... but it is simply a fact, that "Europeans mutate differently":

http://www.unz.com/gnxp/europeans-mutate-differently/

http://biorxiv.org/content/early/2015/02/05/010314

http://biorxiv.org/content/biorxiv/early/2015/02/05/010314.full.pdf

http://www.unz.com/wp-content/uploads/2014/11/kelleyharris.png


Citation: Recent evolution of the mutation rate and spectrum in Europeans, Kelley Harris doi: 10.1101/010314

The above figure is from a preprint, Recent evolution of the mutation rate and spectrum in Europeans, which reports very peculiar results from the 1000 Genomes data. I actually got a preview of the topline finding about a year and a half ago at a Bay Area Population Genomics meeting, but many of the details are new to me. As noted in the abstract the “private European variation is enriched for the transition 5’-TCC-3’→5’-TTC-3’.” The implication here is that different populations mutate differently. The preprint puts this in the broader context of the fact that for a while now there have been conflicts between different rates of mutation inferred from pedigree and whole genome sequencing, and phylogenetic models of divergence of species. At this point the technical details need not concern. Rather, let’s just add that the recent ancient Siberian genome paper confirmed this discrepancy, and strongly supports the contention within this preprint that the mutational rates across the ape lineages are likely to have varied, questioning the validity of an invariant molecular clock.

Frankly I trust Harris to be right about the pattern she sees here. She’s been looking at this data for a few years, so if there was any statistical artifact here I am confident either she or her advisers or colleagues would have caught it. But there are some issues with the attempt to integrate these results about differences in mutational spectrum with population history. Some of these are pointed out in the comments at bioRxiv. Aside from the simple semantic conflation of Early European Farmer (EEF) for Eastern European Farmer, the attempt to suggest that reduced enrichment in northern Europe is a function of Ancestral North Eurasian (ANE) admixture is made less persuasive by pointing to the case of Finns, who are known to have a secondary East Asian admixture which arrived from Siberia more recently. I think that this is not a problem when you see another issue “Because East Asians share a more recent common ancestor with ANE than with west Eurasians.” I do not think this is the dominant view. Rather, ANE and West Eurasians are best modeled as a distinct clade with deep common ancestry as against East Eurasians. See figure 3 of Lazaridis et al. The confusion here matters because the thesis being presented seems to be that ANE lacked the enrichment of a particular mutational class, as modern East Asians do. This is a warranted conjecture if the two formed a clade with West Eurasians as an outgroup, but this is just not the case.

Which brings us to when and why the ancestors of Europeans began to exhibit this particular mutational pattern. As it happens the results show that even without the Finnish sample there is a north-south gradient of enrichment toward the latter. This would support a model where ANE admixture resulted a decrease from an originally higher proportion. That would mean then that the change occurred probably in the interval of 20 to 30 thousand years ago, when we presume the ancestors of West Eurasians and Ancestral North Eurasians diverged. But this is not the only option. One element of EFF ancestry is Basal Eurasian, which happens to be a group which is equally distant from West Eurasians, ANE, and East Eurasians. In other words, Basal Eurasians possibly diverged from all these populations before the primary Out of Africa event ~60 thousand years ago. If the mutational spectrum deviation derives from Basal Eurasians then the gradient could be a function of reduced EEF ancestry in Europe as one goes north. Looking at the difference between the Finnish and Italian samples I do not think this is the case, the variation is too small. The EEF fraction varies a great deal in Europe. So the ANE dilution model actually does seem more plausible.

But there’s a final element to be explored.

Why is there in enrichment in the first place? It turns out that this sort of mutation is very common in melanomas. In particular of interest to me: “Folate deficiency is known to cause DNA damage including uracil misincorporation and double-strand breaks, leading in some cases to birth defects and reduced male fertility.” Folate deficiency can occur when light skinned individuals are exposed to sunlight. It strikes me that the higher mutational load for these particular transitions in Southern Europeans as opposed to Northern Europeans could simply be a function of the fact that they are in sunnier climates. We know that Europeans have become much lighter skinned very recently, so the range of mutations we are seeing may be due to very recent factors. No one knows concretely why Europeans became very light skinned very recently, but these mutations may simply be a side effect of this phenotypic change, which was driven by powerful selective forces.

Citation: Recent evolution of the mutation rate and spectrum in Europeans, Kelley Harris, http://dx.doi.org/10.1101/010314

Addendum: It would have been nice of the 1000 Genomes had at least one Middle Eastern population.

Are Europeans diverging into another species, some kind of "post-modern humans" ???

Angela
27-12-16, 21:54
To point out the obvious: rate of mutation has nothing to do with the nature of mutations.

Joey D
28-12-16, 01:38
Are Europeans diverging into another species, some kind of "post-modern humans" ???

I thought that was the Scientologists?

Angela
28-12-16, 02:22
I thought that was the Scientologists?

Yes, and I'd put them right in the same category too. :)

Judith
12-01-17, 21:44
Could I point out a fact from the original paper at the start of this thread, namely the 3 historical populations were all in semi-isolated areas and would all be somewhat in bred. So the effects of mutations would be worse since many of the population would be carrying a higher load.
Perhaps one of the advantages of this last century is in increased mobility as well as improved medical treatments.