From: mrl@st-andrews.ac.uk (  Michael Ladomery)
Newsgroups: talk.origins
Subject: Re: Divergence of esterase genes
Date: 22 Jul 92 08:33:01 GMT
Organization: St. Andrews University, Scotland.

In article <1992Jul21.120856.13975@usenet.ins.cwru.edu> bk186@cleveland.Freenet.Edu (Julie Thomas) writes:

[deletions]

>Yes, but the gene duplication/divergence story decouples mutation 
>from selection/evolution.  The duplicated gene is not under 
>selection, thus mutations which pop up will remain unless lost by 
>drift.

Depends: the mutation in the duplicated gene could, in some cases,
give rise to a dominant lethal phenotype, or eg to a co-dominant
reduced-fitness phenotype. While the duplicated gene is still able
to produce a gene product (ie it has not become a pseudogene) one
cannot exclude selection.

>| When you say "popping up by pure chance" you imply that it is
>| unlikely. Remember the size of genomes, the plasticity of genomes, 
>| the potential for duplication at various levels (intra-gene;
>| chromosomal; whole genomic duplication etc); the presence
>| of various mobile elements and so on. 
>
>Are you suggesting that these processes make it LIKELY that a DNA 
>sequence will randomly change to form a new, novel protein encoding 
>fragment?  What is your evidence?

Well look in ONE INDIVIDUAL these events are very unlikely, but in
a LARGE population over time, then let me ask you; are you
implying that these events are not possible?

>>2.  If this scenario is true, then we should find, in any genome, 
>>some pseudogenes which encode new proteins.  That is, if the 
>>pseudogene that has sufficiently diverged was cloned out and 
>>placed under the control of some common promoter, and reinserted 
>>back into the genome, we should see the expression of some protein 
>>with a novel function.  Has this been done?  
>
>| A point of definition, since my wording (above) was ambiguous: a
>| pseudogene is *by definition* non-functional, derelicted to varying | degrees; for instance, ib the human globin family, of two known 
>| pseudogenes, one has a frameshift  but is otherwise almost "wild 
>| type"; another is totally wrecked, but it does maintain a TATA box 
>| Therefore what you propose (reinserting the pseudogene next to a 
>| functional promoter) is unlikely to give rise to full-length protein, 
>| let alone a protein with a function.
>
>I agree!!  But the gene duplication/divergence story implies that the 
>genome should contain pseudogenes which do encode novel protein 
>function.  You say it would be unlikely?  Recall what you wrote above:
>
>| When you say "popping up by pure chance" you imply that it is
>| unlikely. Remember the size of genomes, the plasticity of genomes, 
>| the potential for duplication at various levels (intra-gene;
>| chromosomal; whole genomic duplication etc); the presence
>| of various mobile elements and so on. 
>
>So, where are the pseudogenes with novel, functional gene products?

As I pointed out, by definition, a pseudogene can't make a functional
protein, and in most cases can't even make an mRNA.

[deletion]

>| There are documented cases where a very small change can have a
>| large effect on function. 
>
>Yes, for example if an amino acid in the active site is changed to a 
>different type of amino acid, you'll probably lose that function.

The "probably" is important: probably, but not always; the
efficiency of the active site could also improve.

[deletion]

>First, what was measured was the rate of amino acid substitution. 
>The other processes ARE taken into account, for over evolutionary 
>time, they could have and might have occurred.  Furthermore, if you 
>desire to use another protein aside from fibrinogens, be my guest.  
>Since fibrinogens are among the fastest of evolving proteins, it'll 
>simply mean that it takes much longer than 42.5 million years to 
>evolve a new protein.  As for the 25% figure, you might be right.  If 
>you compare Neurospora cytochrome c with that from wheat, they 
>differ by about 50%, yet both still function as cytochrome c.  

That is why such statistics are meaningless, as you imply.
Let's assume the above calculation (25% change is the average change
needed to obtain a new function) is correct. Then you estimate
that on average it takes at least 25 million years. BUT for
example, an exon shuffling event, an internal duplication +
dosage effect, etc etc, could alter the properties of a protein
radically in a short time.

[deletion]

>Yes, but you have uncoupled selction from the whole process.  Recall 
>that the evolving gene is a pseudogene which has no function.  So 
>how do you have a lethal mutation in sequence which has no 
>function?  You don't.  Selection only works AFTER the gene is 
>"reactivated".  And this is basically the scenario where you change a 
>protein by chance in an "all at once" manner, and THEN see if it 
>works in a novel and functional way.  

No; a pseudogene is not an evolving gene, by definition.
But I see what your concern is. Of course, among the pseudogenes
there are those that are so mutated that they are lost: a
genetic fossil; a defunct gene. But a pseudogene that has
appeared only recently (ie a "young" pseudogene) could still retain
some functional parts, some coding areas, some intact exons etc,
eg an ATP-binding domain could conceivably be recombined/transposed etc
elsewhere; admittedly, I wouldn't expect this to happen too often.

>">5.  Finally, what of gene conversion?  Gene conversion is the non-
>>reiprocal transfer of DNA sequence between 'homologous' sequence.  
>>For example, A could serve as the template to transfer it's 
>>sequence to A'.  How frequent is gene conversion as opposed to the 
>>diverging force of mutation?  FAR more frequent (about 1000X more 
>>frequent).Thus, divergence seems unlikely.  
>
>| Remember we are talking about statistical figures here; not *all*
>| mutations are succesfully edited. Moreover, the editing can go
>| two ways: back to the original, or it can go the mutant's way;
>| if I'm remembering correctly, the repair system has no in-built
>| way of "knowing" which is the right sequence.
>
>Sure, but once again this stuff is not applicable given the gene 
>duplication/divergence story.  The whole point to the story is that 
>you can keep the functional gene product at work while the 
>duplicated one can change.  Well, that whole point to the story is 
>lost if you are going to have the duplicated gene sequence convert 
>the original one!  

I should look up "gene conversion" as I can't remember the exact
mechanism; I thought that gene conversion occurred between alleles
at a given locus: if a gene is duplicated and shifted to another
"distant" location, you could hardly expect it to "convert" back.

>By the way, how can one falsify this gene duplication/divergence story?

That's a good question. Let's see if I can answer it. Referring to
p. 147 from "Fundamentals of Molecular Evolution" by Wen-Hsiung Li
and Dan Graur, Sinauer Assoc. Inc. 1991:

The colour-sensitive proteins are required for colour vision.
The blue one is autosomally encoded in monkeys/primates,
whereas the red and green are X-linked. 

Humans and old world monkeys have three colour-sensitive pigment
proteins, blue green and red, and have trichromatic eyesight; the
new world monkeys have dichromatic vision. This is due to the
presence of only one X-linked pigment gene in the New Wrold
monkeys, and of a duplicate in the Old World species;
the duplicates are 96% identical and are postulated to have
duplicated after divergence from the New World monkeys.

I guess if you could find a New World monkey with *the same*
duplication *at the same locus*, and if you could find an
Old World Monkey and observe eg a 60% identity between the
X-linked genes, the above theory should surely be revised.
I apologize if I didn't express this too clearly.

Thanks, Mike.
Newsgroups: talk.origins