Re: [asa] ORIGINS: pseudogenes are overwhelming evidence for evolution...?

John Walley wrote:
<<That section in “Who Was Adam” was written by Dr. Fuz Rana who is RTB’s staff biochemist. His response to pseudogenes is  like that for junk DNA, they question its junk status and instead suggest that it may have been part of God’s design. YEC’s have the same response as well.

Fuz monitors this list and if he see this, he may have something else to add.  I know that some in the RTB base have pressed them to modify their position on this. I think that after Collins and Behe have both come out on this point, they will eventually have to in order to maintain their credibility.

>>

I long ago found I differ with Fuz on the human origins issues.  However, being a researcher in RNA, I would say that the issues of "what is junk" is hardly closed.  Anyway, currently there are many researchers in this field who no longer see the non-protein-coding regions of DNA as "junk".  Perhaps it has even swung the other direction where there is too much hype.  (By the way, in regard to Don's post, if junk is found not to be junk, then shouldn't that mean that the Australian patent doesn't apply to the regions that are found later to have function?)

One thing to remember is that any function in the non-protein coding regions of the DNA have to be transcribed into RNA before much function can be derived.  There are some things that could qualify as "function" that the DNA may do directly with some sort of structure, such as attracting a promoter for expressing a protein or group of proteins, gene rearrangements and supercoiling of the structure.   However, currently, most of the current talk about "junque" DNA is in the hands of RNA.    

There does appear to be a fair amount of non-coding RNA.  Its function is largely unknown (except for the familiar transfer RNA and ribosomal RNA and a few others), but some people think this explains the difference in complexity between ourselves and the flatworm, which shares a similar order of magnitude number of proteins as us.  It also may play a role in biodefense for humans; it certainly plays that role in plants and lower organisms.  There are also LINEs and SINEs (Long/Short Interspersed Nuclear Elements); I would not like to speculate on the purpose of these things,  but, being a physicist by training, I would even argue that things not used for coding can also be "useful". 

I throw in the reminder that we often forget that DNA is a large object folded up into chromosomes.  Some diseases result from aberrant interaction between two chromosomes.  How these things are actually expressed, what attracts the promoter to some inactive regions to start gene expression, mitosis, etc is hardly a well figured out and complete picture.  I'm not arguing from ignorance but from one of serious caution.   

One thing to keep seriously in mind, with __some__ pseudogenes, is that __some__ pseudogenes can be turned on. 

It also reminds me of how many of us professionals program.  We start with an idea, and later on, we have a better one.  We don't erase the original idea right away. For a while at least, we keep it around. It can be useful for checking and comparing.  There are times I've selected out pieces of old code and reused them.  I don't wish to suggest too strongly that the genetic code is just a computer program, but being for the most part self taught in computer programming style, it was a natural "evolution" in my habits that is quite common to many professional programmers.  (If only some of them would develop the habit of writing a few more "comments".... )  It does not seem so unreasonable that biology would have a similar built in set of processes that serve a somewhat similar role.  Actually, the immunity system is already something like a SELIX library used to select out sequences that can nab the offending invader.  

I find that RNA is quite thermodynamically stable, and it is relatively insensitive to mutations.  Of course, there is always a sweet spot in a protein or an RNA and if you hit it, you get a home run, but biopolymers (with 3.5 billion years behind them and constant natural selection) aim at structure unless they are not supposed to have any.  I can get 80% prediction on tRNAs using my thermodynamic model without any other information aside from the possible base pairing. This is comparable to what you would expect with sequence alignment approaches where you would have to find various related species (of various distances) with the same sequence.  Changing from one crude entropy model to another hardly affects the stability, and I don't see much of any big deal about mutations.  Basically, this stuff is pretty stable if it is supposed to be so for some function.
 
What RNA mostly lacks is chemical functional groups, so it cannot even come close to competing with proteins for function.  So to temper this with some reserve, whereas RNA does have function, and there may even have been an RNA world (though I don't commit myself strongly to such a position), even with a comparable stability with proteins, it does not seem to serve a large enzymatic and processing role.  Neither was it quickly identified for its functional role as proteins were.  Its most prominent role is that of ribosomal RNA and the transfer RNA (i.e., transcription and translation). There are some important riboswitches, but the larger part of the problem still usually involves proteins.  It's also important to remember that RNA polymerase  (I, II and III) are proteins. So how RNA can play an important but background role in the lower animals and plants yet suddenly play some enormous role in mammals and especially humans, seems a little out of kilter. But there is, admittedly, some correlation between complexity and the amount of non-coding RNA. 

Perhaps the best thing to end with is what Jack Haas said in jest in another post on a possible 8th bad word: "maybe I am wrong".  The best way to do science is to always make sure that the humility switch is set to the "on" position.

by Grace we proceed,
Wayne (ASA member)

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Received on Sun Nov 4 19:33:43 2007