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Author Topic:   Pseudogenes | Similarity & Dissimilarity
Saviourmachine
Member (Idle past 3554 days)
Posts: 113
From: Holland
Joined: 01-16-2004


Message 1 of 12 (256505)
11-03-2005 12:06 PM


Hi all! Long time no see!
Alpha 1,3 GT
I have a discussion about pseudogenes and the alpha 1,3 GalactosylTransferase pseudogene came up. The assertion was the AiG statement that it was similar in in cow, squirrel, monkey and gorilla. (Gorilla and monkey?) I haven't studied the similarities yet. (If you have done that I would appreciate if you quoted the results.) Anyway, why I am here is because I need some definitions out of the field. I am not exactly a newbie anymore, but I ran out of definitions. So, I need some.
Definitions
I know two terms that I use now as a handle. Orthologous genes are genes that come from one ancestor gene. Paralogous genes are genes that evolved parallel. I am searching for others distinctions and will also use ortho- and para- as prefixes.
There are pseudogenes that are exact copies of each other on an amino acid level. I would name them ortho-acidic. (The alanine, asparagine, cysteine, glutamine, histidine, leucine, etc. elements are in the same order.) There are also pseudogenes that are both pseudogenes of some original gene, but have other mutations that made them pseudogenes. I would name them para-acidic.
Another distinction. There are also pseudogenes that are exact copies all the way down. I would call them ortho-nucleic. There are pseudogenes that although ortho-acidic are not the same on the lowest level (they have only silent mutations as opposed to missense or nonsense mutations). The codons are in the same order. I would call them para-nucleic.
Of course these terms don't apply for pseudogenes only. Also functional genes between species can be compared on these different levels. Does anybody know the "official" terms?
Relevance
Now to relate to the discussion. If a pseudogene shared by cow, squirrel and monkey is ortho-nucleic or ortho-acidic that would be much more remarkable than if it is only para-acidic. And that's what I want to make clear with my definitions. (I secretly expect that they won't be ortho-nucleic or ortho-acidic.)

Replies to this message:
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 Message 6 by Wounded King, posted 11-07-2005 12:44 PM Saviourmachine has replied

  
AdminNosy
Administrator
Posts: 4754
From: Vancouver, BC, Canada
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Message 2 of 12 (256535)
11-03-2005 4:24 PM


Thread moved here from the Proposed New Topics forum.

  
mick
Member (Idle past 4986 days)
Posts: 913
Joined: 02-17-2005


Message 3 of 12 (256939)
11-04-2005 7:33 PM
Reply to: Message 1 by Saviourmachine
11-03-2005 12:06 PM


Hi,
I would just point out that if you are talking about pseudogenes, then the amino acid sequence doesn't matter, because pseudogenes aren't subject to positive natural selection (usually because they aren't transcribed).
saviourmachine writes:
If a pseudogene shared by cow, squirrel and monkey is ortho-nucleic or ortho-acidic that would be much more remarkable than if it is only para-acidic. And that's what I want to make clear with my definitions.
If we are talking about pseudogenes, "para-acidic" and "ortho-acidic" don't mean anything, in evolutionary terms.
Mick

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 Message 1 by Saviourmachine, posted 11-03-2005 12:06 PM Saviourmachine has replied

Replies to this message:
 Message 4 by Saviourmachine, posted 11-07-2005 7:31 AM mick has replied

  
Saviourmachine
Member (Idle past 3554 days)
Posts: 113
From: Holland
Joined: 01-16-2004


Message 4 of 12 (257420)
11-07-2005 7:31 AM
Reply to: Message 3 by mick
11-04-2005 7:33 PM


Pseudogene definitions
Hi mick, of course you're right. But they are called 'pseudogenes' because of their similarity with ordinary, functioning genes isn't it? And it's obvious that a pseudogene is 'para-acidic' compared to (the original) functioning gene. However, I want to have some definitions to compare pseudogenes themselves.
Amino acid sequences and molecular clocks
Also between functioning genes the terms ortho-nucleic and para-nucleic have proper scientific names, I guess. To know the differences between the same genes in two different species on the level of codons gives a handle to define molecular clocks. The nature and amount of mutations among pseudogenes is important. And also their amino acid sequences in this case.
Writing style
I'm sorry if my writing style is that confusing. I know. That's why I definitely want to know the terms that evolutionary biologists use.

This message is a reply to:
 Message 3 by mick, posted 11-04-2005 7:33 PM mick has replied

Replies to this message:
 Message 5 by Mammuthus, posted 11-07-2005 9:36 AM Saviourmachine has replied
 Message 11 by mick, posted 11-08-2005 2:40 PM Saviourmachine has replied

  
Mammuthus
Member (Idle past 6475 days)
Posts: 3085
From: Munich, Germany
Joined: 08-09-2002


Message 5 of 12 (257457)
11-07-2005 9:36 AM
Reply to: Message 4 by Saviourmachine
11-07-2005 7:31 AM


I would avoid trying to make up new terms like para-acidic etc. Here are the definitions that would also apply to pseudogenes
Homologs
. have common ancestry, but the way they are related can vary
(i.e. the reasons they have diverged into different sequences can vary)
orthologs - Homologs produced by speciation. They tend to have similar function.
paralogs - Homologs produced by gene duplication. They tend to have differing functions.
xenologs -- Homologs resulting from horizontal gene transfer between two organisms.

This message is a reply to:
 Message 4 by Saviourmachine, posted 11-07-2005 7:31 AM Saviourmachine has replied

Replies to this message:
 Message 7 by Saviourmachine, posted 11-07-2005 1:59 PM Mammuthus has replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 6 of 12 (257485)
11-07-2005 12:44 PM
Reply to: Message 1 by Saviourmachine
11-03-2005 12:06 PM


Original source?
Was it in reference to this paper :- Roy, 2005. It would be easier if we knew exactly what sequences they were looking at. Simply going by the percentage similarity figures given isn't neccessarily sufficient to build up a reliable molecular phylogeny.
TTFN,
WK

This message is a reply to:
 Message 1 by Saviourmachine, posted 11-03-2005 12:06 PM Saviourmachine has replied

Replies to this message:
 Message 8 by Saviourmachine, posted 11-08-2005 5:22 AM Wounded King has replied

  
Saviourmachine
Member (Idle past 3554 days)
Posts: 113
From: Holland
Joined: 01-16-2004


Message 7 of 12 (257502)
11-07-2005 1:59 PM
Reply to: Message 5 by Mammuthus
11-07-2005 9:36 AM


Word example
I don't want to use other terms on purpose. But, the definitions are not appropriate for the concepts I want to label. Moreover, these definitions embed the concept of ancestory, I am searching for their informatical equivalents.
Let I explain. I will use letters as nucleotides/monomers. Several sequences of nucleotides can code for the same amino acid. An amino acid I will write as a letter. Different amino acids on the nucleotide level(!) I will denote by upper case. (And when necessary marks or italics, etc. can be added.)
I want to label the similarity between QWERTY and QwERTY as opposed to QWEFTY and QSERTY. And likewise between QWeRTY and QWErTY as opposed to QWeRTY and QWéRTY.
I would like definitions that don't connote with the concept of ancestry. It's not under discussion that QWERTY derives from QwERTY, or the other way around. It's also not about their functional properties. How QWeRTY arose is not important. I hope definitions like this do exist...

This message is a reply to:
 Message 5 by Mammuthus, posted 11-07-2005 9:36 AM Mammuthus has replied

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 Message 10 by Mammuthus, posted 11-08-2005 8:33 AM Saviourmachine has not replied

  
Saviourmachine
Member (Idle past 3554 days)
Posts: 113
From: Holland
Joined: 01-16-2004


Message 8 of 12 (257657)
11-08-2005 5:22 AM
Reply to: Message 6 by Wounded King
11-07-2005 12:44 PM


Re: Original source?
Hi Wounded King. I don't think the assertion was very difficult to spend your time with. That's why I insist on these definitions, that I can use in discussing other genes and pseudogenes too.
The statement was this:
quote:
The Alpha-1,3-GT pseudogene includes a substitution at position 726 which is uniquely shared by cows, squirrels, monkeys and gorillas, but is not in humans.
And the article referenced: Gene Sequences Suggest Inactivation of {Alpha}-1,3-Galactosyltransferase in Catarrhines after the Divergence of Apes from Monkeys [U Galili and K Swanson]
The quote is from AiG and misquoted, because the original sentence states not "squirrels and monkeys", but "squirrel monkeys".
This however is my motive to delve a bit into the informatical concepts used in the evolution theory. I am extending my dictionary, but in an autodidact way. That's a bit slow at times. I read terms like mutagenesis, synonymous, codon bias (non-random usage of synonymous codons), monomers, pseudogenization, splicing, weak selection, etcetera. The area is a bit extensive.

This message is a reply to:
 Message 6 by Wounded King, posted 11-07-2005 12:44 PM Wounded King has replied

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 Message 9 by Wounded King, posted 11-08-2005 7:13 AM Saviourmachine has not replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 9 of 12 (257668)
11-08-2005 7:13 AM
Reply to: Message 8 by Saviourmachine
11-08-2005 5:22 AM


Re: Original source?
I had just found that article when I read your post.
One big problem with their argument is that it is only the apes that the gene has been non-functionalised. Since the apes have either 1 or 2 frame shift mutations in the alpha 1,3 galactosyltransferase gene the putative amino acid sequence they would code for is likely to be radically different to that of the Old World monkeys or cow. This isn't even a pseudogene in the cow or squirrel monkey.
It isn't clear in what way they consider this point mutation 'uniquely' shared, certainly it is shared only in those 3 species out of the 11 in the study, but that is quite a way from being somehow unique. In fact since the substitution is of a C for a T, a particularly common base pair substitution, and is only one out of a number of divergent site its existence means practically nothing. One single shared substitution out of an entire sequence hardly seems a sensible metric for claiming that they 'often' contradict evolutionary phylogenies.
TTFN,
WK

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 Message 8 by Saviourmachine, posted 11-08-2005 5:22 AM Saviourmachine has not replied

  
Mammuthus
Member (Idle past 6475 days)
Posts: 3085
From: Munich, Germany
Joined: 08-09-2002


Message 10 of 12 (257693)
11-08-2005 8:33 AM
Reply to: Message 7 by Saviourmachine
11-07-2005 1:59 PM


Re: Word example
Then just say they are all homologous. As soon as you introduce para-, ortho- or xeno you are immediately defining them by their ancestry..even in your definitions. If you want to avoid it, just use the general term for similarity among sequences which is homology. So QWERTY, QwERTY, etc. are homologues...you can then specify what you want to look at like the W-w change.

This message is a reply to:
 Message 7 by Saviourmachine, posted 11-07-2005 1:59 PM Saviourmachine has not replied

  
mick
Member (Idle past 4986 days)
Posts: 913
Joined: 02-17-2005


Message 11 of 12 (257834)
11-08-2005 2:40 PM
Reply to: Message 4 by Saviourmachine
11-07-2005 7:31 AM


SaviourMachine writes:
I don't want to use other terms on purpose. But, the definitions are not appropriate for the concepts I want to label. Moreover, these definitions embed the concept of ancestory, I am searching for their informatical equivalents.
I think it's the other way round, your concepts are not appropriate for the informational content of the pseudogene.
SaviourMachine writes:
it's obvious that a pseudogene is 'para-acidic' compared to (the original) functioning gene
But the psuedogene has lost its coding function. It doesn't have codons, so to speak. This isn't just pedantry, the molecular processes of evolution operating on the pseudogene will be quite different to those operating on the original coding sequence. For example, there will be no third-position bias in mutation rate in the pseudogene; fixed mutations in the pseudogene will be distributed independently of codon position unlike in the original coding sequence. So I don't think it makes much sense to be comparing the codons of a pseudogene with the codons of a coding sequence. The information content of the nucleotide sequence itself may be more informative.
SaviourMachine writes:
To know the differences between the same genes in two different species on the level of codons gives a handle to define molecular clocks. The nature and amount of mutations among pseudogenes is important. And also their amino acid sequences in this case.
Well you don't need to use proteins to model a molecular clock, it can be carried out using nucleotide sequences (for example in the case of SINEs, ribosomal RNA and other elements that are never coded). If you wanted to use a mixture of pseudogenes and coding sequences to model a molecular clock that might prove quite difficult because your model would need to incorporate different substitution models for different classes of sequences in a single alignment.
Mick
added in edit: I found this article which is similar (homologous?) to what you seem to be interested in. The authors are applying a molecular clock to gene families. You probably know this already, but a gene family is a set of genes in a single genome which arose through duplication. Some members of such families may well end up as pseudogenes. But in this case, they are only considering functional members of genes rather than pseudogenes. However I gather their method could be adapted for what you want to do. Hope it's useful!
Molecular Clock Based on the Expansion of Gene Families | Nucleic Acids Research | Oxford Academic
This message has been edited by mick, 11-08-2005 02:46 PM

This message is a reply to:
 Message 4 by Saviourmachine, posted 11-07-2005 7:31 AM Saviourmachine has replied

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Saviourmachine
Member (Idle past 3554 days)
Posts: 113
From: Holland
Joined: 01-16-2004


Message 12 of 12 (259085)
11-12-2005 12:24 PM
Reply to: Message 11 by mick
11-08-2005 2:40 PM


Mick writes:
But the psuedogene has lost its coding function. It doesn't have codons, so to speak. This isn't just pedantry, the molecular processes of evolution operating on the pseudogene will be quite different to those operating on the original coding sequence. For example, there will be no third-position bias in mutation rate in the pseudogene; fixed mutations in the pseudogene will be distributed independently of codon position unlike in the original coding sequence. So I don't think it makes much sense to be comparing the codons of a pseudogene with the codons of a coding sequence. The information content of the nucleotide sequence itself may be more informative.
Hi Mick, you are right. It's not appropriate to speak about it like I do. However, we shouldn't forget to do gene/pseudogene comparisons. I consider mutations like making incisions in a body. If it's living it will be healed quickly, if it's a corpse autopsy is possible. If a pseudogene is not scrambled very much "recognizable codons" are important. I thought their would have been definitions like I suggested, but maybe I'm wrong. Thanks for your study by the way, interesting!
For example this study about nonfunctionalization times:
pANT: a method for the pairwise assessment of nonfunctionalization times of processed pseudogenes.

This message is a reply to:
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