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Author Topic:   Ratio of Deleterious Mutations to Beneficial Ones
PlanManStan
Member (Idle past 1040 days)
Posts: 73
Joined: 12-12-2013


Message 1 of 35 (719306)
02-12-2014 6:59 PM


I was reading a paper (not necesarily the most formal thing you've ever seen, but a paper nontheless) which talked about a computer simulation called Mendel which, when the correct rates of muation, fraction of deleterious muatations, muation rate, selection efficiency, etc., it showed a trend of degeneration, leading to extinction. Do you think this poses a serious problem to evolutionary theory? I'm not well-versed in this kind of stuff (I'm an American high-school student, after all. I'm not well-versed in anything ).

Quote of the Paper I was talking about:

The user manual for
Mendel’s Accountant (www.mendelsaccountant.info)
describes in detail how to input all the relevant data
for different biological situations in the most honest
way possible. Mendel’s specific results depend on
the specific input data used. However the general
patterns which Mendel reveals are surprisingly
consistent—as long as the input data which is
used is even remotely realistic biologically. These
general output patterns are revealed in the example
given below. In this particular example Mendel’s
human default parameters (see the user manual at
www.mendelsaccountant.info) are used, except for the
following exceptions: (a) the frequency of beneficial
mutations is increased 10,000-fold so that the ratio
of deleterious to beneficial is 9:1; (b) for simplicity, all
mutations are made co-dominant.
Although we use here the default mutation rate for
Mendel (which is presently set at ten new mutations
per individual per generation), there is growing
evidence that this should be set about one order of
magnitude higher. We presently use a mutation rate
of only ten just to be generous to evolutionary theory,
allowing for the notion that 90% of the genome might
be irrelevant “junk DNA.” If this example employed
the accepted human mutation rate (>100), the
degeneration described below would be much more
severe and extinction would be rapid. The default
selection pressure used in this example (six children
per female, four of which are selected away every
generation), represents extremely intense selection.

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AdminModulous
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Message 2 of 35 (719308)
02-13-2014 3:58 AM


Thread Copied from Proposed New Topics Forum
Thread copied here from the Ratio of Deleterious Mutations to Beneficial Ones thread in the Proposed New Topics forum.
    
Percy
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Posts: 15494
From: New Hampshire
Joined: 12-23-2000
Member Rating: 4.3


Message 3 of 35 (719314)
02-13-2014 6:57 AM
Reply to: Message 1 by PlanManStan
02-12-2014 6:59 PM


Hi PlanManStan,

There must be a mistake in his program because he says this:

The default selection pressure used in this example (six children per female, four of which are selected away every generation),...

Two surviving children per couple is all it takes for a population to replace itself and would never end in extinction.

--Percy


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PlanManStan
Member (Idle past 1040 days)
Posts: 73
Joined: 12-12-2013


Message 4 of 35 (719316)
02-13-2014 7:22 AM
Reply to: Message 3 by Percy
02-13-2014 6:57 AM


You know, I never thought of that. But wouldn't that be somewhat optimistic, considering that some of the babies will inevitably die of disease, predation, or the like? I was reading about sub-replacement fertility, which is when a population isn't having enough children, and that value can reach 3.4 children per couple in developing nations due to all the dangers.

Source: Wikipedia (yeah, I'm quite the intellectual )


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nwr
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From: Geneva, Illinois
Joined: 08-08-2005
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(4)
Message 5 of 35 (719319)
02-13-2014 8:08 AM
Reply to: Message 1 by PlanManStan
02-12-2014 6:59 PM


I don't know the particular software. But I doubt that it is a problem.

The thing to remember, is that there is actual evidence of evolution occurring. So software models that are inconsistent with the actual evidence are not very persuasive.

Here's the thing to remember with mutations: If a population is well adapted to its environment, then most changes will be changes for the worse. That is, most mutations will be deleterious.

This is just the basic principle that, if you are at the top of the mountain, the only way to go is down.

For a population that is not as well adapted, there is a greater possibility of beneficial mutations. Or, in mountain climbing terms, if you are only part way up, then a random move is as likely to lead you up as to lead you down.


Fundamentalism - the anti-American, anti-Christian branch of American Christianity

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PaulK
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Posts: 12443
Joined: 01-10-2003
Member Rating: 2.5


Message 6 of 35 (719320)
02-13-2014 8:16 AM
Reply to: Message 5 by nwr
02-13-2014 8:08 AM


Aside from the general problem of trusting theoretical models strongly contradicted by the evidence, you should realise that "Mendel's Accountany" was created by the creationist J C Sanford to support his own arguments.
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Percy
Member
Posts: 15494
From: New Hampshire
Joined: 12-23-2000
Member Rating: 4.3


Message 7 of 35 (719321)
02-13-2014 8:18 AM
Reply to: Message 4 by PlanManStan
02-13-2014 7:22 AM


So the next thing you have to know is how he's connecting his mutation rates to the "2 of 6 total offspring survive". That he even mentions such a number makes me think he's structured the problem solution incorrectly. The proportion of offspring that survive should be a function of the mutation rates, not something that is specified.

Also, specifying the number of total offspring (6) is arbitrary. If only 1/3 of offspring survive then an average of 5 total offspring per couple means eventual extinction, 6 total offspring means stasis, and more than 6 means eventual overpopulation.

Look at it another way. Researchers have measured the point mutation rates of many organisms, including humans. It probably ranges from around 1 to a few hundred point mutations per reproductive event, depending upon the mutation rate for the organism and the size of its genome.

Mendel's Accountant says that using the mutation rates researchers have measured results in extinction, so what is Mendel's Accountant trying to say? I can only guess that Mendel's Accountant is saying that since we're not extinct that researchers must have mismeasured the mutation rates. My own guess is that the Mendel's Accountant program has flaws.

Are you a programmer? The program itself can be found at Mendel's Accountant. Someone must have mentioned this program here before because I apparently downloaded it a couple years ago. It's written in Perl and is tiny, far smaller than the software for this discussion board. I doubt it has any of the sophistication they claim, particularly since it arrives at conclusions that are at odds with reality. But if you're a programmer we can look through it together and figure out if what it's doing makes any sense.

--Percy


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PaulK
Member
Posts: 12443
Joined: 01-10-2003
Member Rating: 2.5


Message 8 of 35 (719322)
02-13-2014 8:24 AM
Reply to: Message 7 by Percy
02-13-2014 8:18 AM


quote:

I can only guess that Mendel's Accountant is saying that since we're not extinct that researchers must have mismeasured the mutation rates. My own guess is that the Mendel's Accountant program has flaws.

It's meant to say that species can only last a few thousand years before going extinct, therefore YEC.


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PlanManStan
Member (Idle past 1040 days)
Posts: 73
Joined: 12-12-2013


Message 9 of 35 (719323)
02-13-2014 8:45 AM
Reply to: Message 5 by nwr
02-13-2014 8:08 AM


I see. That's a really good analogy!
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PlanManStan
Member (Idle past 1040 days)
Posts: 73
Joined: 12-12-2013


Message 10 of 35 (719325)
02-13-2014 8:53 AM
Reply to: Message 7 by Percy
02-13-2014 8:18 AM


Unfortunately, I'm not a programmer, I'm actually just a sophmore in high school. However, I am very interested in learning about what you were talking about, with the mutation rates leading to extinction (or rather, what Mendel's Accountant said).
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herebedragons
Member
Posts: 1251
From: Michigan
Joined: 11-22-2009
Member Rating: 5.6


Message 11 of 35 (719326)
02-13-2014 9:25 AM
Reply to: Message 7 by Percy
02-13-2014 8:18 AM


The proportion of offspring that survive should be a function of the mutation rates, not something that is specified.

Shouldn't it be a function of fitness? I see no mention of fitness. Selection pressure should be based on a "fitness threshold" so that organisms below that threshold tend to be eliminated and those above that threshold tend to survive. Selection pressure should not be a fixed number of offspring that die, that doesn't even make sense.

Also selection pressure needs to vary over time, such as with predator / prey oscillations ...

and environmental fluctuations.

There is also no element of randomness to the equation. We all know that not every member of a population will have 6 offspring and that even the most fit individual can be eliminated by a chance event or the even the least fit member survive.

I too downloaded it sometime ago, but it doesn't seem to work now. I don't think it had anywhere near the parameters or the appropriate algorithms it needed to have to make it anywhere near realistic. Maybe you can make your own version of it that works

HBD


Whoever calls me ignorant shares my own opinion. Sorrowfully and tacitly I recognize my ignorance, when I consider how much I lack of what my mind in its craving for knowledge is sighing for... I console myself with the consideration that this belongs to our common nature. - Francesco Petrarca

"Nothing is easier than to persuade people who want to be persuaded and already believe." - another Petrarca gem.

Ignorance is a most formidable opponent rivaled only by arrogance; but when the two join forces, one is all but invincible.


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JonF
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Posts: 3485
Joined: 06-23-2003
Member Rating: 2.8


(2)
Message 12 of 35 (719327)
02-13-2014 9:26 AM


This has been discussed extensively in various places, and a little here.

Mendel's Accountant (MA) is rigged to produce the result that its author desired. It's based on Sanford's oft-debunked "genetic entropy".

------------------------------------------

The simplest way to demonstrate that it's bogus is to consider the fact that there are lots of organisms with generation times that are much smaller than humans. If the MA prediction were correct, mice (with a genome about the same size as humans and 170x the generation time of humans) and Lord know what else would have gone extinct long ago. Sanford replied to this criticism as reported by Jorge Fernandez at the lost TWeb thread:

quote:
"All other things being equal, the population that breeds faster will accumulate mutations faster."

jcs - No, it is just the opposite, short generation times means more frequent and better selective filtering.


Occam's Aftershave destroyed this lunacy:

quote:
Which makes zero sense and is trivially easy to refute with their own program:

Run Mendel with two populations that are identical in every way (i.e genome size, mutation rate, selection pressure, etc.) except make one generation time 2x the other, say two per year year vs. one per year.

If you run them both for 1000 generations, both will end up with the same (lower) fitness level, but the two per year will only take 500 years to get there.

If you run them both for 1000 years, the once per year will end up in the exact same fitness as the first trial, but the two per year will have 2000 generations and end up with an even lower fitness level, if it doesn't just go extinct first.

These guys are busted, and they know they're busted. Now it's just a question of how far they can push this shit and how much money they can make before the errors become well known.


------------------------------------------

The reported runs are with very small population sizes. 1,000 individuals is a population on the crux of going extinct. Again as reported by Fernandez, Sanford claims the effect is seen in larger populations:

quote:
"The really important parameter, and the one that Sanford et al deliberately fudged on, is population size. Populations with small numbers run a much greater risk of accumulating dangerous genetic defects through recombination due to the genetic bottleneck problem. This is a well know issue in population genetics. As it turns out, a population size of 1000 is right around the 'knee of the curve' for extinction. Limiting the population to 1000 will guarantee to drive a population to extinction fairly quickly, p>1000 will still go extinct but much more slowly."

jcs- we have done larger populations - but it gets computationally expensive. What we see is that above 1000, larger populations only improve selection marginally - this does not solve the fundamental problem.


But others report differently, unfortunately mostly in the now-lost TWeb discussion. There's some graphs here (note the link at the end to the raw outputs) for a population of 3,000 and more realistic beneficial mutation rate and maximum beneficial effect 0.01, ten times larger than Sanford's. I'll post one:

Note the increasing fitness, the opposite of what Sanford reported.

------------------------------------------

The program assumes that effect of Very Slightly Deleterious Mutations (VSDMs) (which are not harmful enough to be selected against) is additive; i.e. 100 VSDMs are 100 times as harmful as one VSDM. There's no reason to believe that's true and lots of reasons to believe it's false.

The effect of beneficial mutations is capped at a very low number, 0.1%. This is unrealistic; although beneficial mutations are rare the effect of one can be large. And there's no accounting for Very Slightly Beneficial Mutations (VSBMs). If VSDMs add so should VSBMs. From the manual:

quote:
A realistic upper limit must be placed upon beneficial mutations. This is because a single nucleotide change can expand total biological functionality of an organism only to a limited degree.

"Total biological functionality", whatever that is, is not what determines reproductive success and selection. One single beneficial mutation can, for example, allow one to drink milk in adulthood which can have a strong impact on reproductive success.

Again as reported by Fernandez:

quote:
"The default value for the maximum beneficial value of mutations is much too low. Real-world estimates of positive selection coefficients for humans are in the range of 0.1, not 0.001."

jcs - That is easily re-set, but one has to consider if it is reasonable to realistically build up a genome by increments of 10% (I am speaking of internal complexity - not adaptation to an external environmental factor). I think that is like going up Mt. Improbable using a helicopter.


If anyone can figure out WTF Sanford means there please let me know. Looks to me as if he didn't understand the issue. As Zachriel commented:

quote:
Which goes to show that he doesn't understand his own simulation. Mendel's Accountant doesn't model "internal complexity". It purports to abstract selective differences.

  
JonF
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Joined: 06-23-2003
Member Rating: 2.8


Message 13 of 35 (719329)
02-13-2014 9:51 AM
Reply to: Message 11 by herebedragons
02-13-2014 9:25 AM


I too downloaded it sometime ago, but it doesn't seem to work now

There were major and undocumented bug fixes between 1.2.1 and 1.4.1. Wesley Elsberry reported:

quote:
As demonstrated in the two runs I did comparing the output of v1.2.1 and v1.4.1 on the very same configuration, v1.2.1 has a major error in its handling of beneficial mutations. This has nothing at all to do with memory limits; I also ran both with the default case, and the experimental case used in both merely changed the two parameters as specified by Zachriel above. The memory usage was under 130MB for all cases I ran; the memory I had was sufficient and the simulations ran to completion. Sanford either was given a garbled account of the issue or is deploying a meaningless digression as a response.

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Taq
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Message 14 of 35 (719333)
02-13-2014 11:07 AM


Lower Threshold
In addition to the great Tweb thread, I have found this paper worth mentioning in these discussions.

quote:
Allen JM, Light JE, Perotti MA, Braig HR, Reed DL (2009) Mutational Meltdown in Primary Endosymbionts: Selection Limits Muller's Ratchet. PLoS ONE 4(3): e4969. doi:10.1371/journal.pone.0004969

Primary bacterial endosymbionts of insects (p-endosymbionts) are thought to be undergoing the process of Muller's ratchet where they accrue slightly deleterious mutations due to genetic drift in small populations with negligible recombination rates. If this process were to go unchecked over time, theory predicts mutational meltdown and eventual extinction. Although genome degradation is common among p-endosymbionts, we do not observe widespread p-endosymbiont extinction, suggesting that Muller's ratchet may be slowed or even stopped over time. For example, selection may act to slow the effects of Muller's ratchet by removing slightly deleterious mutations before they go to fixation thereby causing a decrease in nucleotide substitutions rates in older p-endosymbiont lineages.

Methodology/Principal Findings

To determine whether selection is slowing the effects of Muller's ratchet, we determined the age of the Candidatus Riesia/sucking louse assemblage and analyzed the nucleotide substitution rates of several p-endosymbiont lineages that differ in the length of time that they have been associated with their insect hosts. We find that Riesia is the youngest p-endosymbiont known to date, and has been associated with its louse hosts for only 13–25 My. Further, it is the fastest evolving p-endosymbiont with substitution rates of 19–34% per 50 My. When comparing Riesia to other insect p-endosymbionts, we find that nucleotide substitution rates decrease dramatically as the age of endosymbiosis increases.

Conclusions/Significance

A decrease in nucleotide substitution rates over time suggests that selection may be limiting the effects of Muller's ratchet by removing individuals with the highest mutational loads and decreasing the rate at which new mutations become fixed. This countering effect of selection could slow the overall rate of endosymbiont extinction.


In this paper, they looked at asexual endosymbionts which will suffer from genetic "meltdown" at even a greater clip due to Muller's Ratchet. What they found is slightly deleterious mutations built up there was increased negative selection for each additional slightly deleterious mutation. In other words, there is a threshold for the number of slightly deleterious mutations that a genome can incorporate. However, this doesn't result in extinction. Rather, each additional deleterious mutations is much more strongly selected against relative to the same mutations in previous generations. Sanford's model fails to incorporate increased selection as these mutations build up.

Edited by Taq, : No reason given.

Edited by Taq, : No reason given.


  
NoNukes
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Posts: 9333
From: Central NC USA
Joined: 08-13-2010
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Message 15 of 35 (719368)
02-13-2014 5:11 PM
Reply to: Message 5 by nwr
02-13-2014 8:08 AM


Here's the thing to remember with mutations: If a population is well adapted to its environment, then most changes will be changes for the worse. That is, most mutations will be deleterious.

I doubt that this is correct. Perhaps it could be true about organisms who are overly well adapted to some niche environment, but I would not expect that this is true for humans for example.

The fact is that most human mutations are somewhere close to neutral with respect to fitness. We know this because every human has mutations. It may be that most mutations that have some significant fitness impact are deleterious rather than beneficial, but given that such mutations are selected against, I would expect that even lop sided ratios of deleterious vs beneficial mutations would not stop the process of evolution.

Edited by NoNukes, : No reason given.


Under a government which imprisons any unjustly, the true place for a just man is also in prison. Thoreau: Civil Disobedience (1846)

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