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Author Topic:   Mutation and its role in evolution: A beginners guide
molbiogirl
Member (Idle past 977 days)
Posts: 1909
From: MO
Joined: 06-06-2007


Message 46 of 60 (436541)
11-26-2007 11:55 AM
Reply to: Message 45 by Fosdick
11-26-2007 11:29 AM


Re: Epialleles and the germ-soma division
7. Why don't you post your synthesis of this material rather than quoting someone elses?

Because I got bitchslapped by Jadaeris for not posting enough CnP from the literature.


This message is a reply to:
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Fosdick 
Suspended Member (Idle past 3836 days)
Posts: 1793
From: Upper Slobovia
Joined: 12-11-2006


Message 47 of 60 (436542)
11-26-2007 11:58 AM
Reply to: Message 43 by RAZD
11-25-2007 9:14 PM


RADZ writes:

If I try to put this into more general (layman?) terminology, is it fair to say that:

  • Environment during development plus genotype produces a phenotype,
  • The same genotype in a different environment could produce a different phenotype (depending on what is affecting the development of the organisms),
  • Natural selection operates on the phenotype,
  • Thus the effect of the environment on the phenotype can be selected and inherited as long as the population stays in that environment?
Can these phenotype changes not due to genotype become fixed in a population?

Would you still class this as hereditary traits (as in "evolution is the change in hereditary traits in populations from generation to generation") or do we need some new terminology?


Good questions. But I don't think there are conclusive answers to any of them. I would like to know, for example, how "...phenotype changes not due to genotype become fixed in a population." "Fixed"? Fixed where? In what? And when molbiogirl answers simply "Yes" to all of your questions I get the queezy feeling nobody around here really understands how biological evolution works.

—HM


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Fosdick 
Suspended Member (Idle past 3836 days)
Posts: 1793
From: Upper Slobovia
Joined: 12-11-2006


Message 48 of 60 (436543)
11-26-2007 12:03 PM
Reply to: Message 46 by molbiogirl
11-26-2007 11:55 AM


Re: Epialleles and the germ-soma division
molbiogirl writes:

Because I got bitchslapped by Jadaeris for not posting enough CnP from the literature.


mbg, you're too cute to be bitchslapped by a stinkin' admin. Don't let them intimidate you into becoming a googleized lit parrot.

—HM


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Wounded King
Member (Idle past 2430 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 49 of 60 (436545)
11-26-2007 12:08 PM
Reply to: Message 45 by Fosdick
11-26-2007 11:29 AM


Re: Epialleles and the germ-soma division
1. What is an epiallele? Is it an intron?

See this is why I get so frustrated when you try and make out I don't know what I'm talking about. An epiallele is any gene which has had some epigenetic modification substantially affect its expression to the extent that it has a phenotypic effect, i.e. a gene silenced in a particular lineage due to heavy DNA methylation could be considered an epiallele of that gene. The modifications could occur in introns or exons or upstream regions they principally serve to change the local DNA structure in such a way that the expression of the gene is altered. To ask if an epiallele is an intron just suggests that you don't know what either of these things is.

5. How come Wounded King doesn't know about epialleles?

He does, but an epiallele is neither an epigene nor epigenetic material. It is in fact the reason why I asked you to explain what you understood by the term allele and which you somehow managed to come to the completely wrong conclusion about despite your 'allele centric' view.

By changing the way a gene is expressed epigenetic modification essentially creates a further allelic variation of that gene, although the primary genetic sequence is not directly changed, unless you count DNA methylation You were not too 'allele' centric but too 'primary sequence of DNA' centric.

TTFN,

WK


This message is a reply to:
 Message 45 by Fosdick, posted 11-26-2007 11:29 AM Fosdick has responded

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Fosdick 
Suspended Member (Idle past 3836 days)
Posts: 1793
From: Upper Slobovia
Joined: 12-11-2006


Message 50 of 60 (436549)
11-26-2007 12:17 PM
Reply to: Message 49 by Wounded King
11-26-2007 12:08 PM


Re: Epialleles and the germ-soma division
WK writes:

He does, but an epiallele is neither an epigene nor epigenetic material. It is in fact the reason why I asked you to explain what you understood by the term allele and which you somehow managed to come to the completely wrong conclusion about despite your 'allele centric' view.

By changing the way a gene is expressed epigenetic modification essentially creates a further allelic variation of that gene, although the primary genetic sequence is not directly changed, unless you count DNA methylation.


So it's all about allelic variation. Thank you. That is what I thought all along. It's whatever affects the allele in the final analysis. So biological evolution is allele-centric in that regard.

—HM


This message is a reply to:
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Replies to this message:
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 Message 52 by molbiogirl, posted 11-26-2007 1:24 PM Fosdick has responded

  
Wounded King
Member (Idle past 2430 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 51 of 60 (436551)
11-26-2007 12:25 PM
Reply to: Message 50 by Fosdick
11-26-2007 12:17 PM


Re: Epialleles and the germ-soma division
But what constitutes an allele is open for discussion, hence why I asked you what you meant. What you said suggested that you only thought of alleles in terms of variations of primary DNA sequence.

Please be clear on the distinction. This form of 'allelic' variation is not the traditional genetic form, hence the qualifying term 'epi'.

If you think I am agreeing with you but you have a different understanding than I of what is meant by an 'allele' then you might be mistaken. You saying 'That is what I thought all along.' worries me when you have so clearly had no idea what you are talking about 'all along'.

TTFN,

WK


This message is a reply to:
 Message 50 by Fosdick, posted 11-26-2007 12:17 PM Fosdick has responded

Replies to this message:
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molbiogirl
Member (Idle past 977 days)
Posts: 1909
From: MO
Joined: 06-06-2007


Message 52 of 60 (436557)
11-26-2007 1:24 PM
Reply to: Message 50 by Fosdick
11-26-2007 12:17 PM


Re: Epialleles and the germ-soma division
Hoot,

WK's right.

"What is an epiallele? Is it an intron?" shows a marked lack of understanding.

I notice that you are a "retired biologist".

How can a retired biologist ask a question like "What is an epiallele? Is it an intron?"


This message is a reply to:
 Message 50 by Fosdick, posted 11-26-2007 12:17 PM Fosdick has responded

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Fosdick 
Suspended Member (Idle past 3836 days)
Posts: 1793
From: Upper Slobovia
Joined: 12-11-2006


Message 53 of 60 (436560)
11-26-2007 1:30 PM
Reply to: Message 52 by molbiogirl
11-26-2007 1:24 PM


Re: Epialleles and the germ-soma division
Because I'm stupid?

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Fosdick 
Suspended Member (Idle past 3836 days)
Posts: 1793
From: Upper Slobovia
Joined: 12-11-2006


Message 54 of 60 (436564)
11-26-2007 1:50 PM
Reply to: Message 51 by Wounded King
11-26-2007 12:25 PM


Re: Epialleles and the germ-soma division
WK writes:

But what constitutes an allele is open for discussion


You mean an allele is not a variant of a gene?

You saying 'That is what I thought all along.' worries me when you have so clearly had no idea what you are talking about 'all along'.

I'm just trying to squeeze out some of the ambiguity, Wounded. Is there something wrong with that. You know, there were other scientists in history who asked weird questions, such as What is the difference between heat and temperature? or Why couldn't time be a variable and the speed of light a constant? I don't compare myself to those guys, of course, but you seem awfully opposed to my kinds of questions. When I ask you if an epiallele is an intron I picture some poor allele that was shuffled off to the junk yard and forgotten by the genome, but nevertheless trying to send epigenetic signals to its exonic relatives back home.

And I'm pretty sure molbiogirl won't like my conjecture any better than you.

—HM


This message is a reply to:
 Message 51 by Wounded King, posted 11-26-2007 12:25 PM Wounded King has responded

Replies to this message:
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Wounded King
Member (Idle past 2430 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 55 of 60 (436568)
11-26-2007 2:04 PM
Reply to: Message 54 by Fosdick
11-26-2007 1:50 PM


Re: Epialleles and the germ-soma division
You mean an allele is not a variant of a gene?

In this case, given the usual understanding of what consitutes a gene, no. The gene, as represented by a sequence of nucleotides, is not changed. That is why the term epiallele is used, to distinguish it from the normal conception of an allele. An epiallele is formed by a set of extragenomic factors which act upon the gene causing a change in its expression sufficient to impact the phenotype.

I'm just trying to squeeze out some of the ambiguity, Wounded. Is there something wrong with that.

In principle no, in practice yes since you seem to only ever add more ambiguity by bringing up totally irrelevant concepts, i.e. introns.

You know, there were other scientists in history who asked weird questions, such as What is the difference between heat and temperature? or Why couldn't time be a variable and the speed of light a constant? I don't compare myself to those guys, of course

Its funny, because it seems like you just did.

When I ask you if an epiallele is an intron I picture some poor allele that was shuffled off to the junk yard and forgotten by the genome, but nevertheless trying to send epigenetic signals to its exonic relatives back home.

Yeah, like I said, you don't seem to understand at all what we have described to you, even after a couple of pages. If you understood the idea that DNA methylation and histone changes were key components of epigentic modification why would you ask if introns are epialleles. You seem to have at least a tenuous idea what an intron is, in as much as you can distinguish it from an exon, but you still don't seem to understand epigentic modification or the concept of epialleles as distinct from traditional genetic alleles.

TTFN,

WK


This message is a reply to:
 Message 54 by Fosdick, posted 11-26-2007 1:50 PM Fosdick has responded

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Fosdick 
Suspended Member (Idle past 3836 days)
Posts: 1793
From: Upper Slobovia
Joined: 12-11-2006


Message 56 of 60 (436573)
11-26-2007 2:31 PM
Reply to: Message 55 by Wounded King
11-26-2007 2:04 PM


Re: Epialleles and the germ-soma division
WK writes:

In this case, given the usual understanding of what consitutes a gene, no. The gene, as represented by a sequence of nucleotides, is not changed. That is why the term epiallele is used, to distinguish it from the normal conception of an allele. An epiallele is formed by a set of extragenomic factors which act upon the gene causing a change in its expression sufficient to impact the phenotype.


That's nicely stated. But must it be only extragenomic factors that create epialleles? If a gene is coded to add leucine, for example, to build a protein the requisite codon could have any of four nucleotide configurations: CUU, CUC, CUA, and CUG. Why couldn't those differences amount to some sort to epigenetic effect? Obviously there is ambiguity even in the codon itself. Why couldn't junk DNA also have epigenetic roles to play as switches or something? Those would be intragenomic causes of epialleles. Or not?

—HM


This message is a reply to:
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Wounded King
Member (Idle past 2430 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 57 of 60 (436574)
11-26-2007 2:47 PM
Reply to: Message 56 by Fosdick
11-26-2007 2:31 PM


Re: Epialleles and the germ-soma division
Why couldn't those differences amount to some sort to epigenetic effect?

How could they? For a start they are clearly genetic differences. What epigenetic effect do you propose silent mutations may be having? It it is not inconceivable that a regulatory region for one gene might reside in the coding region of another, in that case such a mutation that was silent in the coding gene might affect the regulation of the other gene, but that would just be a plain old genetic effect.

Why couldn't junk DNA also have epigenetic roles to play as switches or something? Those would be intragenomic causes of epialleles. Or not?

Not, because they are Genetic. There is certainly a case to be made that as we understand more about long distance regulatory sequences the traditional conception of a gene and consequently an allele as occurring a specific discrete loci is malleable as mutation megabases away can affect the regulation of a gene to the extent that they could produce a null allele of that gene in some cases. But this widening of the concept does not make them epialleles it just shows that a genetic allele is more complicated than it was traditionally thought to be. Similarly microRNAS, another one from the 'Junk' pile, clearly have regulatory roles and should be considered genes in their own right even thought they don't conform to the traditional idea of a gene being a sequence coding for a protein.

Now those questions weren't bad, nice and simple and not introducing any totally irrelevant and random concepts.

TTFN,

WK


This message is a reply to:
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Fosdick 
Suspended Member (Idle past 3836 days)
Posts: 1793
From: Upper Slobovia
Joined: 12-11-2006


Message 58 of 60 (436596)
11-26-2007 6:30 PM
Reply to: Message 57 by Wounded King
11-26-2007 2:47 PM


Re: Epialleles and the germ-soma division
WK, thanks for your help. I'll admit to you and mbg that I had Disney-level appreciation of the epiallele. What was and still is hard for me to swallow is this notion that epigenetic factors play a role in neo-Darwinian evolution. If epialleles are merely chemically tweaked regular alleles then I am struggling to understand how their epiallelic features get communicated to the offspring. I suppose I just have to go along with those who say that meiosis and fertilization will bring forward what ever is epiallelic about them. I suppose I have to agree that chromatin carries more evolvable information that just genetic code. Am I right?

—HM


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mobioevo
Member (Idle past 4280 days)
Posts: 34
From: Texas
Joined: 12-13-2007


Message 59 of 60 (440869)
12-14-2007 11:43 PM


An example of epigenetics
This is a very interesting threat but from the OP until know it seems the discussion is only on epigenetics and not all of the different types of mutations. I will keep on the topic of epigenetics since the research I conduct is closely related to epigenetics, and I am interested in many aspects of non-Mendelian inheritance. So, I thought I would add an real example of an epigenetic phenomenon to help clarify any misunderstandings on epigenetics.

Methylation and histone modification are not the only sources of epigenetic effects. Some unicellular eukaryotic organisms called ciliates have a cool way of regulating DNA expression through epigenetic phenomenon. I will define epigenetics as reversible, heritable changes in gene regulation that do not change the genotype or the organism. What this means is that gene regulation is modified by some affect outside of the genome and this regulation can be passed on to other generations.

The ciliate Paramecium like all ciliates contain at least two nuclei. Remember the nucleus is where the genetic information of the organism is stored so you can say that ciliates have more than one genome. There is the germ-line nucleus where the genome goes through meiosis and mitosis during sexual reproduction and there is the somatic nucleus that is transcriptionally active.

Paramecium can only multiply through asexual reproduction, but during stressful environments, such as starvation, Paramecium will go through sexual conjugation with another Paramecium. It is thought this occurs so recombination can take place and genetic variation will increase thus allowing the organism more chance to survive in the stressful environment.

Paramecium have two mating types. A mating type can be thought of sexes and only opposite mating types can mate with each other. So, as humans have females and males, Paramecium has O and E mating type. During this sexual reproduction the transcriptionally inactive germ-line nucleus goes through meiosis. Meiosis is a process in which a diploid nucleus is divided into a haploid nucleus. So now there are 2 haploid germ-line nuclei. Conjugation of O and E Paramecium cells take place and one haploid germ-line nuclei is exchanged with the other cell. Now each Paramecium cell has one native haploid germ-line nucleus and one foreign germ-line nucleus. These haploid germ-line nuclei fuse creating a new germ-line nucleus. Notice that both conjugating cells have the exact same genotype in the germ-line nucleus now.

So what goes on during the somatic nucleus during sexual conjugation? This is a very important question as it is the somatic nucleus that creates the phenotype since it is the only transcriptionally active nucleus in the organism. This is the nucleus that produces has its genome transcribed (mRNA is produced), and translated (proteins are produced).

After sexual conjugation and the formation of a new germ-line nucleus, the germ-line nucleus goes through mitosis, a process in which the diploid nucleus is duplicated. Now there are two germ-line nuclei and one somatic nucleus. The somatic nucleus is then degraded one of the germ-line nuclei goes through genome processing to become a somatic nucleus. During this processing the chromosomes in the genome are broken apart into pieces, there is deletion of specific sequences in the genome, and each new pieces of the chromosomes are amplified to a certain number. Sexual reproduction is complete as there is a new germ-line and somatic nucleus.

The cell can then go through asexual reproduction to form two daughter cells. It was expected that after sexual conjugation of O and E mating types that the cells should now produce the same mating type daughter cells after asexual reproduction, but this is not what was found by observation. What was found was that O mating type only produced O mating type daughter cells and E mating type only produced E daughter cells. So this mating type is not inherited Mendelianly.

It was found that mating type was determined by two differential states of the somatic nucleus. Mating type E is caused by a gene being present in the somatic nucleus, while O mating type is caused by the absence of the mating type E gene.

Saving you from the methods but you can read in Meyer 2002 (link below) it was found that during there are epigenetic affects during the development of the somatic nucleus from the germ-line nucleus. During this development the entire genome of the germ-line nucleus is transcribed into RNA, which is then transported into the old somatic nucleus. Remember that the somatic nucleus is made from the germ-line nucleus except that it has many copies of broken up chromosomes, and that these chromosomes are missing pieces that are found in the germ-line nucleus. These RNA molecules then bind in a sequence specific manner to complementary DNA in the old somatic nucleus. RNA that binds is degraded and the RNA that does not bind (since the old somatic nucleus is missing DNA that the germ-line nucleus has) is transported to the new developing somatic nucleus. The left over RNA binds to complementary DNA in the developing somatic nucleus and any DNA it binds to is deleted.

This deletion step is why there are two mating types in Paramecium. A O mating type Paramecium could have an epigenetic mutation in which the deleting RNA molecule base sequence is not exactly complementary to the E mating type gene that is found in the developing somatic nucleus and not delete it from the somatic nucleus genome. This lack of deletion will cause the E mating type gene to be present in the somatic nucleus and thus expression of the E mating type gene causing the E mating type phenotype. The reverse could happen to create the the O mating type from the original E mating type genome.

So in summary the mating types of Paramecium is affected by epigenetics. The underlining genotype of the germ-line nucleus has not changed but the expression of the genome has.

I hope this helps others to understand epigenetics without having to understand methylation and histone modification, things that I am not to familiar with and that put me to sleep. If clarification is needed let me know and I can post some pictures from the below sources.

I'm feeling a thread devoted to epigenetics and its role in evolution should be started as this is a very actively pursued research topic in evolutionary biology.

Sources:
Meyer 2002 may need academic institution to access, email me for a copy. This is a 33 page review.
Mochizuki and Gorovsky same epigenetic action in another ciliate
Paper I wrote on this subject in a graduate course on Non-Mendelian inheritance


  
Wounded King
Member (Idle past 2430 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 60 of 60 (555526)
04-14-2010 4:15 AM


Bump for Delta-9
Delta-9 made a PNT for a thread on epigenetics so I thought I would bump this since it has, sadly, a lot more discussion of epigenetics than it does the basic introductory stuff it was supposed to be about.

TTFN,

WK


  
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