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  Topic: MHC/HLA immune genome mutation rates question< Next Oldest | Next Newest >  
Friar Broccoli



Posts: 5
Joined: Jan. 2014

(Permalink) Posted: Jan. 17 2014,12:06   

Hi;

I am trying to write up a shorter and clearer (so creationists can read it) version of Lenny Flank's argument about mutation rates as implied by the number of alleles in the MHC complex.  I also want this rewrite because (among other things) the creationist response focuses on his use "beneficial" mutations. (See: http://creation.com/bible-t....versity )


In my first draft I began:

_start_
MHC regions are usually less than 2000 bp long in a genome that is 3,000,000,000 bp long.


Observationally we know there are a 100 mutations per generation over the entire genome.

Therefore in a region that is:

- 300,000,000 bp long we would expect one mutation per generation.
- 3,000,000 bp long we would expect one mutation ever 100 generations.
- 3,000 bp long we would expect one mutation ever 100,000 generations.

Since we sometimes see more than 1000 mutations (alleles) in the 2,000 bp long MHC immune complexes this suggests these areas have been mutating for 100,000,000 generations.
_stop_

Here I said to myself 100,000,000 generations seems like way too many, unless (for example the mouse MHC complex looks fairly similar - does it?).  If it does not, what is a more reasonable estimate of the number of generations to achieve the diversity we see in the human MHC complexes?

Also is the observed generation to generation rate of mutations in the MHC complexes much different from that observed in the rest of the human genome?

  
qetzal



Posts: 309
Joined: Feb. 2006

(Permalink) Posted: Jan. 17 2014,21:56   

Keep in mind that each individual can have a mutation. So if you had 100,000 children born in each new generation, you'd expect one new mutation per 3000 bp per generation in the population overall.

I'm sure the actual math is more complicated, but I don't know the details.

  
Alan Fox



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Joined: Aug. 2005

(Permalink) Posted: Jan. 18 2014,04:29   

Your question is cross-disciplinary (biochemistry and genetics involving computer modelling). There's a thread at Dr Elizabeth Liddle's blog that might have some relevance. Joe Felstenstein looks in so you might get some feedback there. You'd be very welcome.

</shameless promotion

  
qetzal



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Joined: Feb. 2006

(Permalink) Posted: Jan. 18 2014,08:41   

It's also worth noting that the initial human population didn't all start with a single MHC allele. MHC traces far back in the mammalian lineage. (Mice have them, for instance.) So the first humans would have had a range of MHC alleles that they inherited from their pre-human ancestors, and they would have inherited a range from their primate ancestors, and so on.

Again, I know it's more complicated, since there are population bottlenecks and alleles get lost etc. but you get the idea.

  
Soapy Sam



Posts: 510
Joined: Jan. 2012

(Permalink) Posted: Jan. 18 2014,12:50   

Polymorphism appears to result from balancing selection, rather than elevated mutation rate, which was the possibility that first struck me.  

http://www.pnas.org/content....ull.pdf

This selection was in train in ancestral pre-human lineages as well, so we descend from a long line of polymorphic species. How it transcends the apparent human population bottleneck of as few as 10,000 individuals, I'm not so sure. But you can't assume a single allele at the 'dawn of man', or any intervening point.

eta,

and you don't just multiply it down a single lineage, as noted by qetzal. Each time a lineage splits, twice as many mutations are separating their MHCs than happen in each separate line; split them a few more times and you could soon get 1000 different versions, even if each individual lineage only experienced a few mutations.

Edited by Soapy Sam on Jan. 18 2014,21:04

--------------
Evolutionists trust entropy for creation of life but are like men who horse a crocodile to get across a river - niwrad.

The organism could already metabolize citrus. Joe G

  
Friar Broccoli



Posts: 5
Joined: Jan. 2014

(Permalink) Posted: Jan. 18 2014,16:08   

[quote=Soapy Sam,Jan. 18 2014,12:50][/quote]
 
Quote

http://www.pnas.org/content....ull.pdf


Thanks for suggesting this article.  It is now obvious to me that I need to read up on mhc in primates and long isolated human populations like Australian Aborigines and Native Americans.  Don't know what I'll find but should see something useful.

 
Quote

This selection was in train in ancestral pre-human lineages as well, so we descend from a long line of polymorphic species. How it transcends the apparent human population bottleneck of as few as 10,000 individuals, I'm not so sure. But you can't assume a single allele at the 'dawn of man', or any intervening point.


I am interested in assuming 8 alleles 4500 years ago (or two 6,000 years ago) and establishing that it is impossible.


 
Quote

and you don't just multiply it down a single lineage, as noted by qetzal. Each time a lineage splits, twice as many mutations are separating their MHCs than happen in each separate line; split them a few more times and you could soon get 1000 different versions, even if each individual lineage only experienced a few mutations.


I suspected this was the problem.  I will probably need to figure out some other way of making the argument.

  
Friar Broccoli



Posts: 5
Joined: Jan. 2014

(Permalink) Posted: Jan. 18 2014,16:20   

[quote=Alan Fox,Jan. 18 2014,04:29][/quote]
Quote

Your question is cross-disciplinary (biochemistry and genetics involving computer modelling).

If computer modelling is required I am screwed.  I need an argument that a creationist can understand intuitively.

Quote

There's a thread at Dr Elizabeth Liddle's blog that might have some relevance. Joe Felstenstein looks in so you might get some feedback there. You'd be very welcome.


If I decide to try and figure out how to make this argument work, I may post a draft there, if I manage to come up with something.

Thanks

  
Cubist



Posts: 349
Joined: Oct. 2007

(Permalink) Posted: Jan. 18 2014,17:05   

Stupid question: What's wrong with Lenny's argument, that you feel it might be worthwhile to work up a different version of it?

  
qetzal



Posts: 309
Joined: Feb. 2006

(Permalink) Posted: Jan. 18 2014,17:07   

Quote (Friar Broccoli @ Jan. 18 2014,16:08)
I am interested in assuming 8 alleles 4500 years ago (or two 6,000 years ago) and establishing that it is impossible.

Sure, you can show it's impossible based on the natural processes we know of. But how do you plan to show that it's impossible to someone who believes in a being that created all life less than 10,000 years ago?

The best you'll manage is to elicit a response like "It's not impossible for God!"

  
OgreMkV



Posts: 3304
Joined: Oct. 2009

(Permalink) Posted: Jan. 19 2014,00:14   

Quote (qetzal @ Jan. 18 2014,17:07)
Quote (Friar Broccoli @ Jan. 18 2014,16:08)
I am interested in assuming 8 alleles 4500 years ago (or two 6,000 years ago) and establishing that it is impossible.

Sure, you can show it's impossible based on the natural processes we know of. But how do you plan to show that it's impossible to someone who believes in a being that created all life less than 10,000 years ago?

The best you'll manage is to elicit a response like "It's not impossible for God!"

This.

I've done the math several times. But it basically means something like 5 new alleles per generation... but only in the HLA factors.

Why wouldn't all the other alleles experience similar rates of mutation?  {oh yeah, god did it, derp}

That kind of mutation rate in the general genome would pretty much destroy the species in a generation.

You can't reason someone out of a position that the didn't reason themselves into.

--------------
Ignored by those who can't provide evidence for their claims.

http://skepticink.com/smilodo....retreat

   
Soapy Sam



Posts: 510
Joined: Jan. 2012

(Permalink) Posted: Jan. 22 2014,16:00   

Quote (OgreMkV @ Jan. 19 2014,06:14)
Quote (qetzal @ Jan. 18 2014,17:07)
 
Quote (Friar Broccoli @ Jan. 18 2014,16:08)
I am interested in assuming 8 alleles 4500 years ago (or two 6,000 years ago) and establishing that it is impossible.

Sure, you can show it's impossible based on the natural processes we know of. But how do you plan to show that it's impossible to someone who believes in a being that created all life less than 10,000 years ago?

The best you'll manage is to elicit a response like "It's not impossible for God!"

This.

I've done the math several times. But it basically means something like 5 new alleles per generation... but only in the HLA factors.

Why wouldn't all the other alleles experience similar rates of mutation?  {oh yeah, god did it, derp}

That kind of mutation rate in the general genome would pretty much destroy the species in a generation.

You can't reason someone out of a position that the didn't reason themselves into.

Obviously, since the MHC is involved in distinguishing self from non-self, I had to artificially raise variation in it as the human population expanded, so that individuals would not all get confused as to who was who.

All the best,

God

--------------
Evolutionists trust entropy for creation of life but are like men who horse a crocodile to get across a river - niwrad.

The organism could already metabolize citrus. Joe G

  
qetzal



Posts: 309
Joined: Feb. 2006

(Permalink) Posted: Jan. 23 2014,11:57   

Quote (Soapy Sam @ Jan. 22 2014,16:00)
Obviously, since the MHC is involved in distinguishing self from non-self, I had to artificially raise variation in it as the human population expanded, so that individuals would not all get confused as to who was who.

All the best,

God

Nice to see a creationist "explanation" with some detail for a change!
:D

  
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