Mutation rate controller?

[SStell]

Hypothesis: There is some mechanism that functions to control the rate of mutation for DNA. Certain regions of the genome are allowed to mutate at a higher rate than other regions. Possibly in the proof-reading mechanism. More proof-reading versus less proof-reading. This would allow highly conserved areas to remain nearly intact generation after generation while other regions would change at the natural rate. Any ideas or data?

[Bender]

Some regions are highly conserved because they are vital and any mutation in them results in the individual not being able to live (or reproduce).

 

Other regions are less critical.

 

So, in a way, you are correct. The "proof reading mechanism" is that those embryos not developing to a reproducing adult fail the "test".

[mistermack]

That's what I thought too. But, that doesn't control the mutation rate. It just axes those mutations later, having the same result in practice. (although it would be more wasteful of embryos).

 

Whether there is a mechanism to reduce the mutation rate could only be answered by a geneticist, or by a genetic textbook.

 

My guess would be there is not. But that really is an uninformed guess.

[Bender]

It controls the mutation rate by axing the lethal mutations. Nature doesn't care about embryos.

 

I'm not a geneticist either, but I think this mechanism is enough to preserve some vital regions and another mechanism is not required to explain a difference in mutation rate.

[Strange]

There are (I think) repair mechanisms that try to correct errors in reproduction. I don't know if these are more effective in some parts of the genome than others...

[mistermack]

Of course, it's not just sex cells that experience mutations. Mutations in other bodily cells can play a part in cancer etc.

[Delta1212]

There are (I think) repair mechanisms that try to correct errors in reproduction. I don't know if these are more effective in some parts of the genome than others...

I think I remember something about differential effectiveness of error correction mechanisms and a degree of optimization to increase effective "evolvability" but that was a while ago, and I don't remember the details well enough to know whether I'm getting that right. I'll dig around later and see if I can find anything.

[SStell]

Thank you for all your input. Just seemed to be a plausible and testable idea.

More proof reading = less change,

Less proof reading = more change.

Could be epigenetic methylation silencing control of 'proof reading gene'.

Different parts of the genome are effected differently. Thanks again.

But natural selection probably does a fine job just on its own as Bender implied.

[Strange]

There is also some redundancy in the coding of amino acids (multiple codons map to the same amino acid). I wonder if there is any way that this can be exploited to make certain genes more robust to changes ...

[mistermack]

Thank you for all your input. Just seemed to be a plausible and testable idea.

More proof reading = less change,

Less proof reading = more change.

Could be epigenetic methylation silencing control of 'proof reading gene'.

Different parts of the genome are effected differently. Thanks again.

But natural selection probably does a fine job just on its own as Bender implied.

The question should really have been posted in the genetics section. This section is evolution, morphology and exobiology.

You would need to know the mechanism of proof reading, to be able to give an informed opinion, on whether some areas could be scanned more or less. The new genes are obviously checked, for repair to happen at all, so it's definitely feasible.

 

I don't agree, Bender, that embryos are so expendable. It depends on the organism, and the point at which they fail.

If it were a human, and they failed at the reproductive stage, that's a huge wasted input from the mother and extended family, giving birth and raising a child, all for nothing, in purely reproductive terms.

Even if the faulty mutation just caused a miscarriage after 8 months, it's still a big cost for no reward.

But to an Oak tree, one lost acorn is nothing to worry about.

[Bender]

 

 

In 1800 the health conditions of our ancestors were such that 43% of the world’s newborns died before their 5th birthday.

source

 

 

 

Among women who know they are pregnant, the average risk of miscarrying before 20 weeks is somewhere between 8 and 20 percent.

source

 

That doesn't take into account the undetected early miscarriages that are suspected to involve chromosomal abnormalities.

 

So first, some of the bad mutations will be eliminated because the sperm is not fit to reach the egg, then, according to some estimates in the article, up to 70% of embryos get rejected before birth.

 

Don't be fooled by current child mortality rates and the taboo that still rests miscarriages: nature does not care for our embryo's or our children.

 

We are still around, though, so it must be worth the cost.

Edited February 9, 2017 by Bender

[mistermack]

Yes, I'm not saying that we don't lose embryos. Really, I'm just saying that because we invest so much in our young, we are probably among the 0.01% of organisms who can afford it least.

 

We think we are a successful species, but in the stone age, there were probably only about a thousand humans in the whole of Britain, so it's a very recent thing that we started to succeed in larger numbers.

 

Yes, we could still afford losses, just, but an error checking mechanism, if it were possible, would probably benefit humans more than almost any other living things.

 

Compared to a Carp, or an Oak tree, or a Coral or Crab, we reproduce incredibly slowly.

The thing is though, that even if something would be beneficial, it doesn't necessarily evolve. There has to be a mechanism, and the feature has to have a benefit all the way from primitive to evolved. Otherwise it won't happen.

 

I'm sure a third arm and hand would be a fantastic benefit to humans, but there's no route for it to happen.

It might be the same with differential error checking.

[Bender]

Yes, I'm not saying that we don't lose embryos. Really, I'm just saying that because we invest so much in our young, we are probably among the 0.01% of organisms who can afford it least.

 

We think we are a successful species, but in the stone age, there were probably only about a thousand humans in the whole of Britain, so it's a very recent thing that we started to succeed in larger numbers.

 

Yes, we could still afford losses, just, but an error checking mechanism, if it were possible, would probably benefit humans more than almost any other living things.

 

Compared to a Carp, or an Oak tree, or a Coral or Crab, we reproduce incredibly slowly.

The thing is though, that even if something would be beneficial, it doesn't necessarily evolve. There has to be a mechanism, and the feature has to have a benefit all the way from primitive to evolved. Otherwise it won't happen.

 

I'm sure a third arm and hand would be a fantastic benefit to humans, but there's no route for it to happen.

It might be the same with differential error checking.

It can happen.

But you are right in the way that such additional limbs are usually not useful enough to stick around.

[mistermack]

It can happen.

But you are right in the way that such additional limbs are usually not useful enough to stick around.

Shudder. Wish I hadn't seen that.

But there's enough for a whole new thread there. Is it genetic? Is there a history of extra arms in the family? Will his kids have extra arms?

I have no idea, but I'd like to know.

Can a species suddenly evolve extra limbs as quick as that? Looking at the world, there seems no sign of it, so maybe it doesn't work.

I'd love to have an extra one, whenever I'm working on something. But looking at him, maybe it wouldn't be worth it.

He's lucky. 20,000 years ago, he would probably just get bullied to death at a very early age.

[Bender]

Shudder. Wish I hadn't seen that.

But there's enough for a whole new thread there. Is it genetic? Is there a history of extra arms in the family? Will his kids have extra arms?

I have no idea, but I'd like to know.

Can a species suddenly evolve extra limbs as quick as that? Looking at the world, there seems no sign of it, so maybe it doesn't work.

I'd love to have an extra one, whenever I'm working on something. But looking at him, maybe it wouldn't be worth it.

He's lucky. 20,000 years ago, he would probably just get bullied to death at a very early age.

I guess we're getting of topic, but if "mutants" are born in the wrong place today, they could still end up being chopped up for alternative medicine. In North Korea, babies with disabilities allegedly get killed too.

 

Apparently, polymelia is genetic:

 

 

These anomalies are usually associated with genetic factors including tamogenes, chromosomes, and environmental agents.

But I guess that throughout evolutionary history, the likelihood of a degenerate extra limb being a disadvantage is much larger than the likelihood of actually getting a fully functional extra limb.

Edited February 10, 2017 by Bender

[Delta1212]

Shudder. Wish I hadn't seen that.

But there's enough for a whole new thread there. Is it genetic? Is there a history of extra arms in the family? Will his kids have extra arms?

I have no idea, but I'd like to know.

Can a species suddenly evolve extra limbs as quick as that? Looking at the world, there seems no sign of it, so maybe it doesn't work.

I'd love to have an extra one, whenever I'm working on something. But looking at him, maybe it wouldn't be worth it.

He's lucky. 20,000 years ago, he would probably just get bullied to death at a very early age.

Depends on what you mean by "evolve." A mutation that generates extra limbs isn't especially unlikely in the grand scheme of things. It happens fairly easily, as you don't have to "reevolve" an entire body part. You just need a mutation that causes the body to build a part it already has the template for an extra time.

 

The issue, of course, is that most body plans are not especially accommodating of extra parts that are more likely to get in the way of how things "normally" work than do anything especially helpful, which is why you don't see extra limbs rapidly spreading through species all the time.

 

In the event that an individual lucks into an extra part that helps more than it hurts, that could spread through the population and eventually become a fixed feature in the genome.

 

So if by evolve you mean just the initial mutation that eventually spreads, then yes, it can happen very rapidly because duplicating existing structures isn't especially difficult mutation-wise. Otherwise, it still takes quite a while for any new feature to spread throughout a population.

[mistermack]

Isn't it more likely though, that an extra arm, as in the linked article, was the result of an egg that started to split into identical twins, but never quite made it? As in the case of conjoined twins. Rather than being a mutation that added an extra arm.

[Essay]

Hypothesis: There is some mechanism that functions to control the rate of mutation for DNA. Certain regions of the genome are allowed to mutate at a higher rate than other regions. Possibly in the proof-reading mechanism. More proof-reading versus less proof-reading. This would allow highly conserved areas to remain nearly intact generation after generation while other regions would change at the natural rate. Any ideas or data?

 

There seem to be many mechanisms that drive evolution, or at least the rapid development of specific adaptations, beyond the regular rate of “new trait” development that comes simply from random mutations.

 

Mechanisms for human genomic rearrangements: [2008]

Non-allelic homologous recombination (NAHR) is mostly mediated by low-copy repeats (LCRs) with recombination hotspots, gene conversion and apparent minimal efficient processing segments. NAHR accounts for most of the recurrent rearrangements: those that share a common size, show clustering of breakpoints, and recur in multiple individuals.

 

NAHR occurs preferentially at the so-called 'hotspots' inside low-copy repeats:

DNA structures capable of inducing double-strand breaks (DSB) (such as palindromes, non-B conformation DNA, minisatellites and DNA transposons) have often been found near the NAHR hotspots, indicating a potential link between NAHR and DSB.

At the same time, extensive linkage disequilibrium studies as well as detailed mapping of single loci clearly revealed that allelic homologous recombination (AHR) also has preferred hotspots.

 

Mechanisms of change in gene copy number: [2009]

Deletions and duplications of chromosomal segments (copy-number variations or CNVs) constitute a major source of variation between individual humans, underlying human evolution and many diseases from mental illness and developmental disorders to cancer. CNVs form at rates far outstripping other kinds of mutagenesis, and appear to do so by similar mechanisms in bacteria, yeast, and human.

 

Human populations show extensive polymorphism in the number of copies of chromosomal segments, and of genes included in those segments, consisting of both additions and deletions. This is known as copy number variation (CNV).

A high proportion of the genome, currently estimated at up to 12%, is subject to CNV.

 

However, additional copies of genes also provide redundancy in sequence, so that some copies are free to evolve new or modified functions or patterns of expression, while other copies maintain the original function. The nonhomologous recombination events that underlie changes in copy number also allow reassorting of exons between different genes by translocation, insertion or deletion, so that proteins might acquire new domains, and hence new or modified activities.

 

I recall reading about a mechanism that duplicates certain genes and then transposes the copies to a new location where they then undergo extra mutation, while the originals maintain normal function, as in the 2009 link above. This was, iirc about 6-8 years ago, thought to be unique to humans and one other primate, and the genes affected were located in an area associated with development of the digestive tract during embryogenesis.

 

This seemed especially interesting at the time, after also having heard that some of the same genes used during embryogenesis of the digestive system were also used later during gestation in the embryogenesis of brain systems. So istm, pressures to change diet could affect brain development in more than just a nutritional manner.

===

 

Googling the terms, indel human unique mechanism of action, brought up the 2008 link above, plus other interesting links.

Following a suggested term from that search, “fork stalling and template switching,” brought up the 2009 link above, plus other....

 

Searching other terms from within these two links, such as recombination hotspot, should be even more interesting.

~

[SamCogar]

then, (early miscarriages) according to some estimates in the article, up to 70% of embryos get rejected before birth.

 

 

Early miscarriages are, more often than not ..... if reported at all, are reported by the pregnant female as simply being a "missed period" ...... and neither their Doctor or any other Health Provider are seldom, if ever, are told about it.

 

Maybe the extremely high "early miscarriage" rate that occurs with human female pregnancies is the reason that "evolution" bestowed an average "28 day menstrual cycle" for all human females.

 

An extremely high "early miscarriage" rate and a "once per year estrous cycle" ..... is not conducive to "survival of the Homo sapiens sapiens species".

Edited February 11, 2017 by SamCogar

[mistermack]

Is there any evidence that miscarriages are the result of genetic problems?

It seems to be a logical thing to happen, but is it actually a fact? I've seen lots of accounts of miscarriages and babies born dead, which were described as perfectly formed, and lots of living babies are born with genetic problems.

 

Maybe the miscarriages DO act as a checking mechanism, but I'd like to see the evidence, before being convinced.

[SamCogar]

 

 

Maybe the miscarriages DO act as a checking mechanism, but I'd like to see the evidence, before being convinced.

 

According to what was posted by Bender, ……..

 

“according to some estimates in the article, up to 70% of embryos get rejected before birth”,

 

 

…… then me thinks the majority of all evidence you are wanting to see …… was disposed of by the “miscarriageing” female. And even if “specimens” were available for research, me thinks it would be a monumental task to determine “why” the body rejected it.

[Bender]

According to the article, which isn't exactly a scientific publication:

 

 

Doctors believe that chemical pregnancies happen for the same reasons as most other miscarriages –- probably because of chromosomal abnormalities in the developing baby. It is hard to know what causes these early miscarriages, however, because it is nearly impossible to retrieve any samples for chromosomal testing.

I don't know more about it then what I can find on the internet. It sounds at least plausible that some genetic defects would result in miscarriage and some wouldn't.

 

Another article from the same site. I don't know how reliable it is, but at least it sources peer reviewed journal publications.

 

 

Estimates suggest that anywhere between 40 and 75% of all miscarriages can be explained by random genetic problems in the developing baby.

Edited February 12, 2017 by Bender

[mistermack]

It seems that all the articles say something similar. It seems to be a generally accepted estimate that about half are caused by chromosomal abnormalities, although whether that's the result of proper studies, or just a general opinion is unclear.

 

You would think that studies would have been done on this subject, but after looking at Google search results, they all seem to say that about half of early miscarriages are gentetic, but nobody mentions how they know that.

 

Maybe it's considered obvious, from looking at the fetus. Or maybe studies have been done, but nobody is quoting them.

 

It seems to be a high failure rate, but maybe, considering the dangers of childbirth, it's an evolutionary sound method of protecting a mother from the dangers of going full term, just to produce a baby that is not viable long-term

Humans have just about the most dangerous childbirth of any mammal, due to the size of our heads, so maybe screening embryos in the uterus evolved giving a positive survival benefit.

 

It would be interesting to see how we compare to chimps or gorillas.

[Bender]

All animals with pregnancy have miscarriages.

Interestingly, the reasons stated are environmental rather than chromosomal. Of course, a very early miscarriage would possibly be even harder to study in animals, especially when they have multiple healthy embryos at the same time.