differences in mutation rates

[Buckaroo Banzai]

I would like to know a bit about that. I think (or, more properly saying, I guess) that do exist differences of mutation rates between different organisms genomes (between genomes of organisms with the same quantity of genes, not counting a bigger genome that would have more mutations because of a larger area of possible occurence), but what about differences between different areas within a genome of a organism? I'm not referring to fixation of a mutation due to natural selection, but, maybe, the effect that it may have, the development of system that keeps low mutation rates, by a more rigorous efficiency of the DNA copying process, or by a more rigorous correction of errors in these areas.

And isn't necessary that this differences between mutation rates of different genome areas would had been due to a evolved system "for" it... maybe the oposite relation of cause and consequence could have happened (if such thing of differences in mutation rates in a genome exists), ie., the genome had incidentally less mutations in some areas than in others, so then would be selected eventually some organisms where traits of high selective importance evolved controled by genes which were fortunately distributed in the areas of the genome with (already extant) less incidence of mutations kept the basis of the trait safe, with few "variables" of control of the trait in other areas with more frequent mutations, giving some variability that would be more probably not-deleterious than mutations ocurring in genes that control the basis of the trait.

Also a hybrid history would be - hypothetically - possible, starting with the second one, and later reinforced by natural selection. But, if such thing exists. Does that exist? What's that mechanism, how does it work? These things I said could happen?

 

[spuriousmonkey]

Obviously different parts of the genome are subject to different rates of mutations because some parts are more important than others and stay more conserved.

But that is not what you mean I presume.

 

[John Connellan]

Obviously different parts of the genome are subject to different rates of mutations because some parts are more important than others and stay more conserved.

Really? And how does that happen?

 

[spuriousmonkey]

Really? And how does that happen?

These parts encode functional domains or regulator sequences. Or Whatever what is important.

 

[Buckaroo Banzai]

Obviously different parts of the genome are subject to different rates of mutations because some parts are more important than others and stay more conserved.

But that is not what you mean I presume.

(wow, my english is sucking that much?)

Anyway, that's what I meant, but only in part.

I know that there are highly-conserved sequences, but the conservation of these sequences is because is more unlikely to mutations occur in these sequences? - that's what I mean. Or are these sequences subject of the same rates of mutations, but these mutations are (nearly) allways deleterious, thus the conservation of the sequence is just due to elimination of these mutations via inviability/death of the carrier of the mutation? Thus the sequence remains highly-conserved, but the rate of mutations remains the same of any other sequence, what changes is the rate of "viability" of these mutations. That's is what I use to hear that really happens...

What you said was more or less a "yes" to the first possibility, if that's the case, how exactly that works, how the genome (or whatever) manages to fix mutations more rigidly on specific areas, or avoiding the ocurrence itself?

Short after I posted this, I coincidently droped in archives of a discussion elsewhere mentioning "hot spots"... I guess that's what I'm talking about... how the genome (or whatever) defines the "temperature" of its own areas?

What would be required to this is that the different "mutability" of specific sequences to be a heritable trait (thus passive to selection).... but I don't know even how (not why, which is because these sequences would be more important) some sequences could be more "mutable" than others in the same organism, the chemical mecanism that allows these differences... I thought that the chemical mechanism for DNA replication and correction would be the same for the whole genome, blind to the selective importance that any trait may have phenotypically. It could only "know" the selective importance of some sequences if the the "carefullness" with specific sequences were itself a trait passive of selection (maybe controlled by other sequences... but maybe not necessarily, with each sequence "taking care" of how important is to not mutate... I guess.)

 

[ElectricFetus]

I can't remember, was it like 1 error in 2 million bp for prokaryotes replication and something better for eukaryotes, I'm sorry I kind of drunk now, I’ll pull out the books on that later.

 

[spuriousmonkey]

What you said was more or less a "yes" to the first possibility, if that's the case, how exactly that works, how the genome (or whatever) manages to fix mutations more rigidly on specific areas, or avoiding the ocurrence itself?

The genome doesn't really fix itself in this manner although there is constant proofreading and checking and repair. It is more the case that natural selection is not very favourable to mutations in for instance these important functional regions. If in a protein an aminoacid is changed into another (because of a none-neutral basepair mutation) this can have serious consequences for the folding of the protein, for the interactivity with other proteins, for the enzymatic activity of the protein etc.
Any organism with these kind of mutations will not do well on a functionanal level and hence will be selected out. Conserved regions in a gene are therefore always of interest to a biologist because they signify functional importance.

I do believe that certain regions on the chromosome are more prone to mutation for a physical reason, but I can't remember why and how.

 

[John Connellan]

I do believe that certain regions on the chromosome are more prone to mutation for a physical reason, but I can't remember why and how.

Right, coz thats the question I was asking. How exactly is it less prone. Perhaps if we find that out then we can go over to the immortality thread and tell them how to stop aging

 

[spuriousmonkey]

Some regions are of course more tightly packed than others, and some regions are methylated and others aren't.

Could that make a difference?

 

[spuriousmonkey]

Mutation rates differ among regions of the mammalian genome.

Wolfe KH, Sharp PM, Li WH.



In the traditional view of molecular evolution, the rate of point mutation is uniform over the genome of an organism and variation in the rate of nucleotide substitution among DNA regions reflects differential selective constraints. Here we provide evidence for significant variation in mutation rate among regions in the mammalian genome. We show first that substitutions at silent (degenerate) sites in protein-coding genes in mammals seem to be effectively neutral (or nearly so) as they do not occur significantly less frequently than substitutions in pseudogenes. We then show that the rate of silent substitution varies among genes and is correlated with the base composition of genes and their flanking DNA. This implies that the variation in both silent substitution rate and base composition can be attributed to systematic differences in the rate and pattern of mutation over regions of the genome. We propose that the differences arise because mutation patterns vary with the timing of replication of different chromosomal regions in the germline. This hypothesis can account for both the origin of isochores in mammalian genomes and the observation that silent nucleotide substitutions in different mammalian genes do not have the same molecular clock.

We propose that the differences arise because mutation patterns vary with the timing of replication of different chromosomal regions in the germline.

hmm...but this article is fairly old. I will try to find something more recent.

 

[spuriousmonkey]

This one is also quite interesting considering the topic of the thread:

Mutation rates in mammalian genomes.

Kumar S, Subramanian S.



Knowledge of the rate of point mutation is of fundamental importance, because mutations are a vital source of genetic novelty and a significant cause of human diseases. Currently, mutation rate is thought to vary many fold among genes within a genome and among lineages in mammals. We have conducted a computational analysis of 5,669 genes (17,208 sequences) from species representing major groups of placental mammals to characterize the extent of mutation rate differences among genes in a genome and among diverse mammalian lineages. We find that mutation rate is approximately constant per year and largely similar among genes. Similarity of mutation rates among lineages with vastly different generation lengths and physiological attributes points to a much greater contribution of replication-independent mutational processes to the overall mutation rate. Our results suggest that the average mammalian genome mutation rate is 2.2 x 10(-9) per base pair per year, which provides further opportunities for estimating species and population divergence times by using molecular clocks.

So apparently the mutation rate per time is similar in all genes in all species. Does that mean that every species can basically evolve at the same pace? There is no difference between mouse and elephant?

Edit - here is a quote from the discussion of this article:

The absence of significant correlation between the mutation rate and generation time is likely to prompt a reassessment of the generation time effect hypothesis, in which errors in DNA replication in germ-line cells is considered to be the major source of mutation (11, 13). This hypothesis predicts a higher mutation rate in species with shorter generation time (e.g., mice as compared with humans). This is because, as is thought currently, species with the shorter generation length will undergo more germ-line cell divisions per year and thus accumulate a larger number of replication errors in unit time, which would lead to a larger mutation rate per unit time in those species. However, the relationship of the number of germ-line cell divisions and the mutation rate clearly is not linear as is indicated in the difference in the ratio of the male/female mutation rate in primates and rodents. Primates show a male/female mutation-rate ratio (37, 38) that is almost the same as seen in rodents even when the ratio of the number of germ-cell divisions in males and females is almost 3-fold higher in humans as compared with mice. Therefore, our results suggest that replication-independent mutational processes (e.g., DNA methylation, recombination, and repair mechanism) may play a greater role as a source of mutation than that anticipated earlier (4, 38, 39).

 

[John Connellan]

So apparently the mutation rate per time is similar in all genes in all species. Does that mean that every species can basically evolve at the same pace? There is no difference between mouse and elephant?

No. Mutation does not completely explain evolution rates.

 

[ElectricFetus]

How about sex and mutation, does that do the job?

 

[Buckaroo Banzai]

The genome doesn't really fix itself in this manner although there is constant proofreading and checking and repair.

And the efficacy of this process doesn't differ along the genome? (being more "careful" for some regions)... I think you already said that not....

I do believe that certain regions on the chromosome are more prone to mutation for a physical reason, but I can't remember why and how.

That's what I wanted to know, expressing briefly, a physical reason for some regions on the genome to mutate differently... and also if this differences of mutability could vary at the individual level and be heritable, ie.: variants with heritable different rates of mutability for the same region. Just in the same way that variants can vary sightly in the size of a trait, and this variation can be heritable.
The second part I probably could know if I knew why and how.

 

[John Connellan]

How about sex and mutation, does that do the job?

No, u need Natural Selection to explain evolution rates. that is why sharks don't seem to have evolved very much even though their DNA is still subject to similar mutation rates to ours.

 

[ElectricFetus]

John Connellan,

I thought you were saying that things don't evolve, and thus you should consider other factors.

The rate of mutation is a more fixed then it is variable, one in so many bps will suffer a deletion, insertion, duplication, inversion, point, ect. And only a percentage to these will get or can get repaired by repair mechanism. A environment can be made more Mutagenic by adding mutagens. The Rate of evolution is something very different though.

 

[spuriousmonkey]

And the efficacy of this process doesn't differ along the genome? (being more "careful" for some regions)... I think you already said that not....




That's what I wanted to know, expressing briefly, a physical reason for some regions on the genome to mutate differently... and also if this differences of mutability could vary at the individual level and be heritable, ie.: variants with heritable different rates of mutability for the same region. Just in the same way that variants can vary sightly in the size of a trait, and this variation can be heritable.
The second part I probably could know if I knew why and how.

Check out the references I gave.

 

[John Connellan]

John Connellan,

I thought you were saying that things don't evolve, and thus you should consider other factors.

That I don't believe in evolution? U should know me better by now!

If a mouse and an elephant have different mutation rates, it does not mean their rates of evolution have to be the same. How could I have made that sentence any clearer than what i wrote before?

Do u agree with this?

 

[ElectricFetus]

no the mouse and elephant probably have same mutation rate per individual, there rate of evolution though may be different.

 

[John Connellan]

I was just answering Spurious' question k?!