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Beneficial mutations vs harmful

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Beneficial mutations vs harmful

Postby Doom » Mon Oct 07, 2013 6:20 am

Firstly I am NOT posting this for an ID/evolution/Creation/every-other-belief-under-the-sun debate. I just want to know the answer :)

My understanding:
The majority of mutations are neutral (I read 70%)*, the next majority are harmful, and the smallest percent are beneficial.
Of these beneficial mutations, many are actually destructive, they just happen to help in that particular environment (eg. sickle cell anemia).

My question:
In the face of so much destruction, how can occasional beneficial/constructive mutations add up evolution?

My Conclusion:
I just don't get it.

*even these neutral mutations are destructive, they just aren't in the particular environment :) btw correct me if I'm wrong
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Postby JackBean » Mon Oct 07, 2013 1:45 pm

I'll say only two short things
1) nowadays are the organisms (and proteins and their sequences) rather optimized for what they do. However it was not always like that. So in the beginning bigger proportion of the mutations could be beneficial
2) if there is about one mutation per new being in humans (may be much higher in other organisms) and you have several new beings every hour, why wouldn't it just add up? imagine there are several generations of mice each year with several offsprings in each.
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Postby Doom » Mon Oct 07, 2013 9:53 pm

on the first one, ok. On the second one though, wouldn't the harmful/neutral mutations add up even faster though?
This is what my entire question was about, the harmful mutations adding up faster than the beneficial mutations.
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Postby biohazard » Tue Oct 08, 2013 12:39 pm

Neutral mutations, as per their definition, are neutral and have no effect so they are neither favored or penalized by natural selection. Of course it is very difficult to determine what mutations are truly neutral, but I guess the common definition is that we cannot see any effect caused by it (that does not mean that there wouldn't be some tiny effect, good or bad).

Harmful mutations tend to weaken the organism in its given environment, so they gradually wane or disappear altogether from the gene pool due to organisms without such mutations superseding them. Thus harmful mutations rarely gain much room in the gene pool.

Beneficial mutations, albeit rare, tend to accumulate in the gene pool because they are favored by natural selection. Thus, despite so much "destruction" everywhere, beneficial mutations are eventually the ones that have best chances to prevail. However, in steady environments this kind of accumulation of tiny beneficial traits is extremely slow.

However, like JackBean wrote, if the environment becomes drastically different, then certain beneficial mutations can become predominant much quicker.

I'll try to give an example: most modern Europeans and their descendants have a mutation that causes them to fail to turn off the production of lactase enzyme after infancy. This was a harmful mutation if it happened to a stone age person, because their body would waste energy (even a tiny bit counts in the long run!) by producing an enzyme that had no use for an adult. Thus this kind of mutation probably never became common in the stone age man, just like it is uncommon in many parts of the world even today. However, when certain animals, such as the cow and the goat, were domesticated, a person with this kind of mutation suddenly gained a clear advantage over other people by being able to consume protein and energy rich milk of these animals. This person would then have an edge over other people of his time and have more children and better health, and thus the mutation quickly spread over areas where milk producing domesticated animals were kept, but failed to spread to areas where this was not a case.

So like you said, many "beneficial" mutations can be harmful as well - be it the sickle cell gene or the ability to produce lactase - it all depends on the environment of the given organism.

Sickle cell aenemia and lactase production are one of the most simple examples, since both traits can emerge after a relatively small changes in the genome, but the same overall idea applies to any genetic change: its benefit/harm is always judged against its environment, which then determines what kind of chances that new genetic element has to propagate or die off.

In a static environment few mutations stand a chance to do well since organisms living there are already rather well optimized, but then again few environments are truly stable.
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Postby wildfunguy » Wed Oct 09, 2013 3:30 pm

I think I understand where Doom is coming from. Most neutral mutations are neutral because they have no effect on phenotype. When mutations do effect phenotype, they're usually harmful. Many mutations to the phenotype have both positive and negative consequences, but there are certain environments where their positive consequences outweigh their negative consequences. Perhaps such mutations could be called "temporarily beneficial". For example, maybe the sickle cell allele, which is more common where malaria is rampant, will be weeded out once malaria is no longer a threat to that population. i.e. it's "temporarily beneficial".
Of course, sickle cell is an example of heterozygote advantage, so the normal allele is maintained in the population. But there could have been other examples of "temporarily beneficial" mutations throughout our history. If those mutations conferred enough competitive advantage during their beneficial period, the normal form may have been weeded out. Thus such "temporarily beneficial" mutations might pose a threat to the long-term integrity of the genome.
However, gene flow may be the answer here. Long-term beneficial mutations may be present in all populations, whereas the temporarily beneficial mutations are only present in a few populations. Gene flow can always reinsert the long-term forms once the beneficial period is over.
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Re: Beneficial mutations vs harmful

Postby Coelacanth » Sun Oct 13, 2013 6:08 am

The majority of mutations are neutral (I read 70%)*, the next majority are harmful, and the smallest percent are beneficial.
Of these beneficial mutations, many are actually destructive, they just happen to help in that particular environment (eg. sickle cell anemia).


Neutral mutations may or may not be proliferated as they have no beneficial or disadvantageous aspect.


In the face of so much destruction, how can occasional beneficial/constructive mutations add up evolution?


A beneficial mutation would feasibly aid in the survival of a given species, and the advantage would then allow that specimen to proliferate its genetic information containing the beneficial mutation.

I just don't get it.

*even these neutral mutations are destructive, they just aren't in the particular environment :) btw correct me if I'm wrong


An easy method of comprehending the process of beneficial as opposed to disadvantageous mutations in regards to evolution is by assuming that the beneficial mutation in question spells ''HOUSE''. We first have H. There are 26 letters in the alphabet, so there exists a 1 in 26 probability that the next letter (mutation) shall be a ''O'' - a neutral or beneficial mutation. There is now the same probability that the third letter shall be a ''U''. If it is not, then we shall have ''H.O'', which remains neutral or advantageous and becomes a fully beneficial gene (given the correct environment) when the ''word'' is spelt.

You will not be seeing desert-dwelling animals evolve flat, oar-like tails for aquatic locomotion because that would be a neutral or disadvantageous mutation, and it would not aid in the hypothetical species's survival, so it would not be proliferated. If there was a sudden rise in sea level, then this mutation over time would aid in the survival of the species's given environment, so it would evolve to accomodate the new environment challenge.
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Re:

Postby Cat » Tue Oct 15, 2013 12:18 am

JackBean wrote:1) nowadays are the organisms (and proteins and their sequences) rather optimized for what they do. However it was not always like that. So in the beginning bigger proportion of the mutations could be beneficial.


Human hubris. No evidence to support those statements...
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Re: Re:

Postby JackBean » Tue Oct 15, 2013 11:50 am

Cat wrote:
JackBean wrote:1) nowadays are the organisms (and proteins and their sequences) rather optimized for what they do. However it was not always like that. So in the beginning bigger proportion of the mutations could be beneficial.


Human hubris. No evidence to support those statements...

Really? How is that hubris? Unless you want to promote creationism, you will probably agree that in the past, when new enzymes arrived, they were much less suited for their function than after the billions of years of evolution.

biohazard wrote:In a static environment few mutations stand a chance to do well since organisms living there are already rather well optimized, but then again few environments are truly stable.

I see what can be the problem. What I meant was rather the enzyme-reaction relashionship, than something like organism-environment.
But still, the organisms tend to be adapted to their environment, so unless there are some big changes (either in the environment or the organisms moving to new niche), they are probably somewhat adapted.
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Re:

Postby ChrisHoStuart » Tue Oct 15, 2013 2:19 pm

JackBean wrote:2) if there is about one mutation per new being in humans (may be much higher in other organisms) and you have several new beings every hour, why wouldn't it just add up? imagine there are several generations of mice each year with several offsprings in each.


Quite so! They do add up; and this is the basis of measuring genetic distances and inferring phylogeny.

This if very effective; because the number of mutations is much larger than one per new individual.

A recently published estimate is 70 new mutations per diploid individual in humans. See: Rates and fitness consequences of new mutations in humans (2012) by Keightley PD, in Genetics. 2012 Feb;190(2):295-304. doi: 10.1534/genetics.111.134668

The paper is available in full and has a lot of useful discussion.

They also estimate another important number; the deletrious mutations per generation, as being a bit over 2.

Some implications... the great majority of mutations are neutral; such mutations will accumulate generation by generation, and many will become fixed. This is the basis of "genetic drift".

Another implication: the deleterious mutation rate (more than 2) is high. The real force of the original question of the thread is -- how come these detrimental mutations don't accumulate?

There's two basic answers to that.
(1) "Purifying selection". Detrimental mutations need not be immediately fatal, but over time they (by definition) tend to show up in fewer descendants than neutral mutations, and hence are much more likely to be eliminated by drift rather than fixed.
(2) "Compensation". Some detrimental mutations do manage to become fixed; but there is not a corresponding continuous decline in fitness, as other mutations (beneficial) may arise to compensate.

When it comes to the actual numbers and calculations, it still seems difficult for selection to adequate handle 2 new detrimental mutations in each individual; and another very important concept is "synergistic epistatis"... a complex phrase I had to look up as well. Basically, it means that genes tend to work together and in such a way that fitness does declines less rapidly with with a few detrimental mutations, and declines more rapidly as more accumulation. Basically, I guess this means organisms are tolerant of a suitably small number of detrimental effects.

Jack made the point that living things are very well adapted, or optimized, for what we do. This isn't hubris. It's data; it's a fundamental observation about living things which cries out for an explanation -- and evolution is the biological explanation for the superb adaption we observe in living things.

But things aren't perfect, and further more there are a continuous stream of "errors" in the replication of genetic information from generation to generation; a substantial amount of which is detrimental. They do accumulate; but the more they accumulate the more opportunity there is for compensatory mutations to bring the basic fitness level back to a kind of running equilibrium in fitness.

There's a lot more to be said on this; and there are differences between species. But basically; the answer to the original question is...

(1) Most mutations are neutral (well over 95%), and they certainly do accumulate. This is the basis for useful measurements of genetic difference.

(2) Mutations that carry detrimental consequences do also accumulate, but much much more slowly, because they tend to be eliminated by selection. This is called purifying selection.

(3) A certain small amount of accumulation of detrimental mutation occurs, but this also gives scope for mutations that can benefit by compensating in some way; and so a small amount of functional difference accumulates over generations, giving also continuous change in the face of a continuously changing environment, all implying any particular trend in increasing or decreasing fitness.

Cheers -- Chris
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Re: Re:

Postby ChrisHoStuart » Tue Oct 15, 2013 2:52 pm

ChrisHoStuart wrote:... and so a small amount of functional difference accumulates over generations, giving also continuous change in the face of a continuously changing environment, all implying any particular trend in increasing or decreasing fitness.


urk... missed the editing window to fix this. That last phrase should be:
all WITHOUT implying any particular trend in increasing or decreasing fitness.
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Re: Re:

Postby wildfunguy » Sat Oct 19, 2013 9:18 pm

ChrisHoStuart wrote:But things aren't perfect, and further more there are a continuous stream of "errors" in the replication of genetic information from generation to generation; a substantial amount of which is detrimental. They do accumulate; but the more they accumulate the more opportunity there is for compensatory mutations to bring the basic fitness level back to a kind of running equilibrium in fitness.

After reading your post, I spotted an erroroneous intuition I've had about this issue. We have this intuition that natural selection is working at a fixed rate. If the mutation rate increases beyond the rate of natural selection, then mutations should begin accumulating. Accumulating, i.e. appearing at a higher frequency with each subsequent generation. However, natural selection is not stuck at a fixed rate.
Let us imagine that we can measure the extent of harmful mutation for any given individual. Hypothetically, there should be a tolerable level (1-10), and individuals beyond that level will not survive to reproduce (>10).
Harmful mutations could accumulate in an unusually healthy population of 1s and 2s. However, once the harmfulness accumulates to the point where some people are 11s or 12s, people start to die prematurely. Even if you speed up the mutation rate, all that will do is increase the death rate (i.e. the rate of natural selection).
So the mutations are flowing through the population like muck through a stream. Creationists have this intuition that natural selection works at a fixed rate, like a detoxifying agent. If you're pumping muck into the river at a faster rate than the detoxifying agent, the muck should being accumulating. But natural selection is more like a membrane, only allowing a set amount of the muck to pass through. The more muck there is spilling into the river, the more filtering the membrane does.
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Postby wildfunguy » Sat Oct 19, 2013 9:38 pm

To put it simply...
The intuition is that natural selection can only block a certain amount of mutation.
But in actuality, natural selection can only let through a certain amount of mutation. Creationists have it backward.
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