Butterfly unlocks evolution secret

[Biochemist]

I have been reading a bit more about the 0.14 number I mentioned. It is actually the number of mutations pr effective genome pr sexual generation. The effective genome is the part of the genome where deleterious mutations are likely to have an effect (i.e, the coding parts of the DNA). Mutations in non-coding parts of the DNA is left out in that number.

 

The comparable number in humans is 1.6, so humans actually have a higher mutation rate than Drosophila pr sexual generation....

Thanks for the clarification, MS. Are you saying that, on average, each human generation from a single set of parents averages 1.6 mutations in the protein encoding coding portion of the DNA? This would mean (since US famileis averange less than 2 children) that the majority of US human children have at least one mutation. Is this what you are saying?

[MortenS]

Yes,Bio, that is what the number means. Each human will on average be born with 1.6 mutations in the coding regions of DNA.

 

Just remember that most of these 1.6 mutations will be silent, due to the redundancy in the genetic code.

 

Also remember that there is a chance for copying errors in each cell division in the line from zygote to gamete. Humans have many cell divisions between zygote and gamete compared to lets say Drosophila.

[Biochemist]

Yes,Bio, that is what the number means. Each human will on average be born with 1.6 mutations in the coding regions of DNA.

Mort- I would love to see the reference on this. Most proteins are dysfunctional with most single-amino-acid residue substitutions. This would mean that most folks are producing dysfunctional proteins. Can you point me to a reference on this?

 

Thanks.

[MortenS]

Well, I have actually seen the number vary from about 1-3 mutations in the coding region pr diploid zygote.

Some references:

Overview:

http://www.ias.ac.in/jgenet/Vol83No3/231.pdf

 

Various estimates:

 

http://www.genetics.org/cgi/content/full/156/1/297

 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10577911&query_hl=7

 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9950425&query_hl=7

 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12497628&query_hl=7

 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8364591&query_hl=7

 

 

In general, the estimated deleterious mutation rate in humans is estimated to 1-3 x 10^(-8) mutations per nucleotide pr haploid generation. The total haploid human genome consists of 3 x 10^9 base pairs. The number of total mutations pr haploid genome pr generation is therefore 30-90 mutations pr haploid gamete. Each diploid zygote therefore have an estimated 60-180 mutations in their whole genome (coding + non-coding).

 

If we assume that the mutation rate is the same in both coding and non-coding areas of the genome (and this is big assumption, as it is quite possible that there is different mutation rates in coding and non-coding areas of the genome), we can use the ratio of coding to non-coding nucleotides to estimate the number of mutations in the coding regions.

 

About 97% of DNA is classified as non-coding at present, which means we have ~3% coding DNA.

 

~3% of 60-180 mutations in the whole diploid genome then equals 1.8-5.4 mutations in the coding region of the diploid genome, under the assumption that the mutation rate is the same in coding and non-coding DNA (of course, this assumption might not be entirely valid, but then it means that the mutation rate in non-coding DNA is higher, since many estimates of mutation rates in humans are based on counting mutations occuring in affected individuals born by unaffected parents)

 

I must note that these are calculations are made by me, and I might have overlooked a few things in that process.

[Biochemist]

This is great info, Mort. Thanks. I am going to look this over and get back to you.

[Biochemist]

Well, I have actually seen the number vary from about 1-3 mutations in the coding region pr diploid zygote....I must note that these are calculations are made by me, and I might have overlooked a few things in that process.

Mort-

 

After an egregiously long delay, I finally took the time to look over the links that you passed along. This is a really outstanding discussion. Thanks for the links.

 

I agree with the premise of the original authors (e.g., Haldane) and the subsequent researchers that the incidence of genetic change from parent to offspring is in the range you cited (60-180 genetic alterations per generation for humans).

 

What really intrigues me, given the reasonably advanced state of our knowledge (compared to Haldane's era in the 1930's) is that there is still an explicit assumtion that these changes are mutations. We are now aware of a number of mechanisms that directly alter the genome (e.g., transposons, reverse transcriptase, etc) in between cell division events. It could be readily argued that a significant fraction of the germ cell genetic alterations are not mutations (i.e., random errors ) but rather they are the result of some extant genomic altering mechanism.

 

Ergo, if a daughter species has a genomic change that increases complexity, and expresses enough phenotypic change to be characterised as a different species, it is only an assumption that the change was driven by mutation. It could well have been driven by a proscribed genomic alteration.

 

Overall then, the rate of genomic change probably ought to be considered to be the sum of mutation plus proscribed genomic change. The interesting question (to me) is whether the behavior of the genomic modification mechanisms is "random" or predefined. If the behavior is predefined, it would suggest that the genomic structure of daughter species is maintained as meta-information in the genomics of the parent species.

 

You mentioned above that the genetic migration of insects (with respect to insecticides) is rapid enough that resistance is assumeed in a relatively small number of generations. The resistance is empirically true. The question I would ask is whether the rapid reaction to enviroinmental toxins is an "engineered" genetic facility or a truly random response.

 

Thoughts?

 

Thanks again for the thoughtful response above.

[pmaust]

Bio, this is not a false premise. We would not have species without speciation. When discussing evolution we need to talk the language of the theory. You may not agree that speciation happens but then you should also not use the term "species", since it *does* imply that speciation occurs to separate them.

 

We have the fossil record and also DNA testing as evidence that speciation has occured. What we don't have as of yet is speciation under observation - which is to be expected because these things take time.

 

For those not into the evolution theory, here is a good starting point:

http://evolution.berkeley.edu/evosite/evo101/VC1fEvidenceSpeciation.shtml

 

The link to the original article didn't work for me. :doh: One of the things that has always puzzled me is that I would think that we should see speciation. Here is why. With all the diversity of life on this planet, it doesn't seem reasonable that every species was on the same speciation schedule(not saying there is one) with all other life. That fact that we don't see speciation at least once in a while is interesting. For example, I wonder if speciation is induced environmentally or by some other external condition. Perhaps if the environment remains stable, speciation won't occur. Maybe this could be tested. What if a species of insect were selected and raised in a controlled envorionment that was stressful but not leathal and we observed them over a period of many generations. I wonder if that has been done? Or, am I way off here? :confused:

 

Anyway you smart people, don't be too hard on me for my naive questions. :naughty:

[Biochemist]

...I wonder if speciation is induced environmentally or by some other external condition. Perhaps if the environment remains stable, speciation won't occur. Maybe this could be tested. ...Anyway you smart people, don't be too hard on me for my naive questions. :confused:

Certainly not dumb questions.

 

It is certainly difficult to encapsulate anything that looks like speciation in the lab unless we have literally millions (and probably billions) of offspring to test. There are some models like this with bacteria, but even with anything as large as an ant, it would be tend to be time and space prohibitive. All that being said, MortenS (our resident entomologiust) probably knows of some examples like this with insects.

 

We do have some reasonable examples of speciation through genetic drift (i.e., selection of recessive alleles in small populations) but that is not via mutation. I think that the ensatina salamander is probably one of the best examples. Link on the topic here:

 

http://www.actionbioscience.org/evolution/irwin.html

 

My personal opinion is that speciation via mutation is uncommon, and that the general mechanism lies somewhere else. We tend to default to a mutative mechanism becasue 1) mutations certainly happen, 2) some are not lethal, and 3) we can't really think of anything else.

 

But it doesn't map all that well to the fossil record (e.g., punctuated equilibrium) and direct evidence for speciation via mutation is remarkably thin. I have hypothesized in this forum that the genomic metagenes (that is, specifications for new genes that do not exist in the parent) for daughter species may well be present in the parent species, and that speciation itself is programmed. That may be more consistent with the fossil record, but it just pushes the compleity problem back further in time to earlier life forms.

 

Oh well.

[pmaust]

We do have some reasonable examples of speciation through genetic drift (i.e., selection of recessive alleles in small populations) but that is not via mutation. I think that the ensatina salamander is probably one of the best examples. Link on the topic here:

 

http://www.actionbioscience.org/evolution/irwin.html

 

My personal opinion is that speciation via mutation is uncommon, and that the general mechanism lies somewhere else. We tend to default to a mutative mechanism becasue 1) mutations certainly happen, 2) some are not lethal, and 3) we can't really think of anything else.

 

But it doesn't map all that well to the fossil record (e.g., punctuated equilibrium) and direct evidence for speciation via mutation is remarkably thin. I have hypothesized in this forum that the genomic metagenes (that is, specifications for new genes that do not exist in the parent) for daughter species may well be present in the parent species, and that speciation itself is programmed. That may be more consistent with the fossil record, but it just pushes the compleity problem back further in time to earlier life forms.

 

Oh well.

 

Thanks for the response and the great link. I find your statement that speciation itself might be programmed interesting. By programmed do you mean it simply as a trigger mechanism for speciation?

 

Thanks!

[MortenS]

Mort-

 

You mentioned above that the genetic migration of insects (with respect to insecticides) is rapid enough that resistance is assumeed in a relatively small number of generations. The resistance is empirically true. The question I would ask is whether the rapid reaction to enviroinmental toxins is an "engineered" genetic facility or a truly random response.

 

Thoughts?

 

Thanks again for the thoughtful response above.

 

As you probably have understood, I am of the opinion that the mutations behind insecticide resistance is indeed random. The question is just what we mean by random :confused:

 

The fact that resistance occurs so rapidly in insects like flies and mosquitoes are due to several factors: 1. our insecticides usually target particular proteins, so a change that disables the protein or alters the protein in the region where our insecticides attack the protein, will usually lead to a higher survival rate in a regime with high selection pressure.

2. Loss of function evolves much more rapidly than gain of function (because there are many more ways to be nonfunctional than functional). Sometimes loss of function, functions as a change of function.

3. Short generation time (usually less than a month in insects) causes any successful mutation to be spread rapidly in the population)

4. Large population size, combined with high fecundity (often several hundred eggs during one females lifespan) gives many chances for a mutation to occur. And it only has to occur once, then remain in the population via genetic drift, until a selection regime (e.g. us starting to use insecticides) sets in that increase the fitness of individuals containing the mutation. Then natural selection takes over, and make the mutated allele increase in frequency. Once the mutation has happened, the spread in insect populations c

 

 

;)And now to my smiley:

I do not mean that all mutations have to be random at the DNA level. Just that the mutations are random with respect to natural selection. That is, the organism, or its genome has no way of "knowing" which particular mutation is necessary to increase the fitness of the organism in a particular environment. For example, it is known that mutations happens more frequenctly in regions of the DNA where there are repeated short sequences (like CGCGCGCGCGCGCGCGCGCGCGCGCGCG or similar sequences), since the chance of a mismatch increases in repeated sequences). I can also think of many other "non-random" causes of mutations, that are still random with regard to the effect the mutation has on the organism.

 

I will have to come back to this...

[Biochemist]

Once again, outstanding post, MS-

The fact that resistance occurs so rapidly in insects like flies and mosquitoes are due to several factors: 1. our insecticides usually target particular proteins...

2. Loss of function evolves much more rapidly than gain of function...

3. Short generation time...

4. Large population size...

I undersand the prolific reproduction of insects is a driver for adaptation, and I understand and agree with your specific use above of "random" in the context of survival in a populaiton.

 

I think the issue hanging in my miind is that there just are not really all that many proteins that we are available to block. As I understand it, most pesticides (at least the early ones) are/were neurotoxins (like carbaryl). There are only so many possible ways that an enzyme that makes neurotransmitters or the protein in a receptor site can be mutated and still be functional. There are also a limited number of proteins that can be disabled, and still have a viable species. This is analogous to noting that there are only so many parts you can pull off your BMW and still have it run. I don't know how many functional enzymes bugs have, but humans only have about 300,000. You can't take out very many of them, and still have viablity.

 

But the capacity for insects to respond to chemical challenge suggests that the little machines have an extraordinary capacity for functional permutations. That is, it is as if they have either extra parts, redundant parts, or a tendency to deploy workarounds. This feels more like a feature of the insect than a question of happenstance within prolific reproduction. The insects would still need prolific reproduciton to use the "feature" , but it sure seems to be a feature, not an accident.

 

Am I being too vague?

[Biochemist]

...I find your statement that speciation itself might be programmed interesting. By programmed do you mean it simply as a trigger mechanism for speciation?

I launched a thread on this a while back (and got beat to pieces by Buffy and Bumab- it was pretty good thread) so you might look for it. I think it was called "Punctuated equilibria theories" because I was trying to explain the relatively rapid introducion of phyla into the fossil record.

 

My (completely unsubstantiated) hypothesis is that the general mechanism for production of new body plans (like new phyla) is based on an expression of information form the parent species genome that was not previously expressed as a phenotype. That is, new body plans might show up just because the parent species invoked a genetic change process. The process never goes through natural selection if the genes are not expressed phenotypically.

 

The likely trigger for such an event would be the expression of a recessive allele, since it seems to happen most frequently in small populations. In this case, the recessive allele would not direectly show as a physically expressed gene in phenotype. Rather, the gene would invoke a genetic alteration process, enzymatic or otherwise. This would mean that natural selection was not related to produciton of new phyla. Preexisting genetic code (that was never previously expressed) defined it.

 

This is pretty far fetched, but we really have no idea how so many new body plans (usually identified as phyla) showed up during the Cambrian explosion. There really was not enough time for a mutative gradualism to occur. And genetic drift alone really can't explain the introduction of entirely new body plans in the timeframe we have in the fossil record.

 

The upshot: The parent species might not look much like the daughter species. There is some preliminary evidence for this, in that the genetic maps for the few species that we have sequenced do not track particularly well with phenotype. That is, species that look alike phenotypically might not be very close genetically and vice versa.

 

The more genomes that we sequence, the more my (pet) theory will be supported (or eradicated). Just remember that if I am right, you saw it here first folks. And I will make Buffy buy me a beer.