Does neutral theory assert that majority of mutation are deleterious?

[microsat]

"The neutral theory of evolution (Box 1) is the accepted null model for the

evolution of DNA sequences. It postulates that the vast majority of

nucleotide sequence differences observed between species do not affect

function, and that many or most mutations in nucleotide sequence are

deleterious and therefore subject to negative natural selection. Therefore

they never (or only rarely) come to fixation. An alternative possibility,

which might apply at the phenotypic level, is that most differences between

species are adaptive and fixed by positive selection. "

 

excerpted from http://www.nature.com/nrg/journal/v7/n9/full/nrg1940.html

 

How to understand the above paragraph from NATURE REVIEW.

Is it correct or wrong?

Does neutral theory assert that majority of mutation are deleterious?

If it does, how to measure if a mutation is 'deleterious' or not?

[CharonY]

Is it correct or wrong?

It is not THE but an accepted model and is especially used as a null model (in order to describe non-neutral frequency changes). There are also slight variations of this model that appear to describe some phenomena better than the original proposed on (by Kimura, I think).

 

 

Does neutral theory assert that majority of mutation are deleterious?

Almost all theories assume that. The main difference between neutralism and pure selectionism is that the neutral theory assumes that the amount of favourable mutation is too low , whereas selectionism proposes that the amount of favourable mutation is sufficient to explain all molecular evolution. In both cases neutral and deleterious mutations are in the majority, though.

 

 

If it does, how to measure if a mutation is 'deleterious' or not?

It is always determined via the fitness (often expressed via a selection coefficient).

[lucaspa]

"The neutral theory of evolution (Box 1) is the accepted null model for the

evolution of DNA sequences. It postulates that the vast majority of

nucleotide sequence differences observed between species do not affect

function, and that many or most mutations in nucleotide sequence are

deleterious and therefore subject to negative natural selection. Therefore

they never (or only rarely) come to fixation. An alternative possibility,

which might apply at the phenotypic level, is that most differences between

species are adaptive and fixed by positive selection. "

 

excerpted from http://www.nature.com/nrg/journal/v7/n9/full/nrg1940.html

 

How to understand the above paragraph from NATURE REVIEW.

Is it correct or wrong?

Does neutral theory assert that majority of mutation are deleterious?

 

I was able to get the article. They did a weird job of stating neutral theory. This quote is before the one you gave.

 

"These observations are best explained by the neutral theory of molecular evolution postulated by Motoo Kimura in the late 1960s (Ref. 16) (Box 1). According to this theory, the rate of evolutionary change in genomes is largely determined by the mutation rate and the extent to which mutations are weeded out by negative selection. The changes that are driven to fixation because of their survival or reproduction advantages are relatively rare compared with the large number of neutral changes."

 

What they are saying is that individuals with deleterious mutations are not going to survive or have kids, therefore they are not going to change the base sequences of the population. Only neutral mutations or beneficial ones will become "fixed" -- the first by chance and the second by positive selection.

 

It is in this context that you have to understand your question. No, most mutations are NOT deleterious. Instead, of the mutations that become "fixed" (in every member of a population) so that they show up when the genome is sequenced, none of them are deleterious. That is what they are trying to say when they say "deleterious and therefore subject to negative natural selection. Therefore they never (or only rarely) come to fixation."

 

In general, the article is trying to figure out which of those 40 million sequence differences between humans and chimps are significant in terms of making chimps different from humans. Is it most of them? "An alternative possibility, which might apply at the phenotypic level, is that most differences between species are adaptive and fixed by positive selection. " Or is it only a few of them, with most of the differences being neutral and been fixed by chance? "In addition to these approximately 35 million point mutations, other differences include approximately 5 million insertions, deletions, duplications and inversions14. ... This means that only a small fraction of all DNA sequence changes between humans and chimpanzees are relevant to the functional differences between the species, making the identification of non-neutral changes a daunting task. Few studies have been able to bridge the gap between DNA sequence differences and phenotype differences. "

 

Usually Neutral Theory is stated differently:

 

"The neutral theory of molecular evolution, championed by Motoo Kimura and further elaborated by several other population geneticists, provides the "null hypothesis" agaisnt which data on molecular variation are compared. In other words, patters of molecular variation are assumed to be explicable by genetic drift of selectively neutral mutuations unless they depart significantly from neutral theory." Futuyma, Evolutionary Biology, pg 628, 1999

 

"In Chapter 11, we will describe the "neutral theory of molecular evolution". This theory describes the fate of purely neutral mutations, i.e., those that neither enhance nor lower fitness." Futuyma, pg 273

 

I can't get the full article until Monday at work, so I'm not sure what is going on here. My first impression is that the authors of the article made a strawman version of the neutral theory.

 

If it does, how to measure if a mutation is 'deleterious' or not?

 

It's difficult. By it's very nature, a brand new mutation is only in one individual. If it is very deleterious, it kills the individual or prevents it from having offspring. In this case, the mutation is only in one individual in one generation, which makes it very hard to detect in wild populations. You need a laboratory population where you do genotyping on every individual. Such studies have been done and these types of deleterious mutations are very rate, only 2.8 per 1,000 mutations.

 

However, if the mutation is only slightly deleterious, the individual will be able to have offspring and the mutation will persist at a very low frequency in the population for several generations. During that time, the frequency will start to decline faster than it would if it were neutral.

[microsat]

It is not THE but an accepted model and is especially used as a null model (in order to describe non-neutral frequency changes). There are also slight variations of this model that appear to describe some phenomena better than the original proposed on (by Kimura, I think).

 

 

 

Almost all theories assume that. The main difference between neutralism and pure selectionism is that the neutral theory assumes that the amount of favourable mutation is too low , whereas selectionism proposes that the amount of favourable mutation is sufficient to explain all molecular evolution. In both cases neutral and deleterious mutations are in the majority, though.

 

 

 

It is always determined via the fitness (often expressed via a selection coefficient).

 

I am just wondering how we call this theory as neutral theory if it asserts majority of mutations are deleterious or slightly deleterious and these deleterious and slightly deleterious mutations should be determined via the fitness of the NATURAL SELECTION.

 

Does anyone know what neutralists and selectionsit think respectively about what proportion of all mutations is adaptively neutral, deleterious(lethally and slightly delterious), and advantageous, respectively? What's the difference of their thoughts about the mutation proportion question?

[foodchain]

I am just wondering how we call this theory as neutral theory if it asserts majority of mutations are deleterious or slightly deleterious and these deleterious and slightly deleterious mutations should be determined via the fitness of the NATURAL SELECTION.

 

Does anyone know what neutralists and selectionsit think respectively about what proportion of all mutations is adaptively neutral, deleterious(lethally and slightly delterious), and advantageous, respectively? What's the difference of their thoughts about the mutation proportion question?

 

That’s basically decided by natural selection, of which mutations are beneficial or not. This also can fall into the category of micro to macro evolutionary scales. You see, you get your genetic variance, which according in a very general sense to natural theory and of course which is observed is mutations do not always have to have any real particular impact, which in itself is product of more then one variable, such as the fact that more then locus like two actually can be found in an organism that perform the same function, this can go down to the gene level also. Neutral theory also has more sway the larger a population gets, and it also works in tandem with genetic drift. To get back on track natural selection is a mechanism outside of the organism, its not as if inside the genetics of a say a type of bird species knows it needs a certain type of beak to make it. This is why you can find variation of the beak, and of course the one expressing currently the best fitness being the beak selected naturally. Basically when you step on an insect, you could be unknowingly lowering, or raising, or having no real impact on the fitness of that population, another reason why I feel compelled to hate the hunters that want to go for the best fit deer leading the rest around.

 

You have to think though that from bacteria to say frog, the amount of genetic variance is so great that neutral theory obviously is more effective on certain evolutionary scales, simply being it was variance through time evolutionarily speaking that to a frog, which of course has a biology more adaptive to say how it survives rather then being completely random to its niche, as in seals for instance or other mammals adapted to living in the sea no longer hold a biology indicative of being land based, even while vestigial structures on many levels of the seal shows it once did.

[CharonY]

I am just wondering how we call this theory as neutral theory if it asserts majority of mutations are deleterious or slightly deleterious and these deleterious and slightly deleterious mutations should be determined via the fitness of the NATURAL SELECTION.

 

You are a bit confusing things here (and I was a bit unspecific). The theory assumes that most mutations that are fixed (and not every occurring mutationas you might be thinking ) are in fact neutral.

The "neutral" thus refers to fixed mutations and not to new mutations.

 

 

The selectionistic theory states that the fixed mutations are the result of positive selection and therefore have to be benevolent.

In other words, the neutral theory assumes that random effects (like e.g. genetic drift) are the major forces in molecular evolution and not natural selection.

Also keep in mind that we are talking about molecular evolution and are not yet on the phenotype level of the organism. On that level it is generally agreed that selection plays the major part.

 

If we take a look a new (random) mutation that has not been fixed in the gene pool yet then chances are that they are mostly neutral or deleterious. In general, a single point mutation is usually neutral. Accumulation (in case of high mutation frequencies) usually leads to a decrease in fitness.

Advantageous mutations are in all models (known to me) extremely rare. The neutral theory states that these are so rare that they do not play a major role in molecular evolution. So if you make a plot of mutation frequency vs the selection coefficient (in this case as a measure of fitness), you will find that in the neutral theory the frequency is high for neutral and negative selection coefficients, and low to non-existent for positive coefficients. In selectionism you will find a high frequency for negative selection and a low one for both 0 and positive selection coefficients. Meaning that if mutations out of these are getting fixed, they'll have to be advantageous.

The only theory that has an equal (low) frequency for negative and positive mutations is the pan-neutralism. Here it is stated that all mutations are neutral. This theory is almost surely refuted, though.

[lucaspa]

I am just wondering how we call this theory as neutral theory if it asserts majority of mutations are deleterious or slightly deleterious and these deleterious and slightly deleterious mutations should be determined via the fitness of the NATURAL SELECTION.

 

Did you read my response? You are dealing with ONE paper and how they stated it, not "we call this theory ... if it asserts". As I noted, neutral theory is not stated as the authors of the paper stated it.

 

Does anyone know what neutralists and selectionsit think respectively about what proportion of all mutations is adaptively neutral, deleterious(lethally and slightly delterious), and advantageous, respectively? What's the difference of their thoughts about the mutation proportion question?

 

Yes. You can look at this paper that measured deleterious mutation rate == lethal or adversely affecting lifespand and reproduction:

PD Keightley and A Caballero, Genomic mutation rates for lifetime reproductive output and lifespan in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 94: 3823-3827, 1997

 

This study documents the rate of deleterious mutations in the worm C. elegans. Because they are hermaphroditic, the authors were able to separate the worms and run parallel populations descended from a single individual. By maintaining independent sublines, the effect of selection could be minimized, and thus the deleterious mutations could be kept in the population. Lethal mutations are still lethal, but the experimental design allows accumulation of deleterious mutations (as well as neutral mutations) and then the effect on lifespan and production of viable offspring, both of which are measurements of fitness. The estimated deleterious mutation rate per haploid genome (the whole organism) was 0.0026, or 2.6 per thousand. This is about 100 fold *less* than previously found for Drosophila. All in all, deleterious mutation rates are very low, considering that total mutations are about 1 per genome (individual).