Irreducible Complexity in Interacting Systems

Dr. Albert Voie declared in his recent comment:

I noticed that the lac repressor binds to a palindromic sequence. The DNA binding is performed by two identical dimers that is bound together strongly by multiple interaction.

There are four principle clusters of amino acids in the tetramer that comprise the interface between the two monomers of each dimer <> : residues 70-100, 221- 226, 250-260, and 275-285 <>. Point mutations in any of these clusters, excluding 250-260, will result in only the monomeric form of the repressor. The binding between the two dimers is extremely strong due to the number of interactions.

One could ask the question; what came first, the palindrome or the protein-protein interactions. Both seems to be required to form a complete tetrameric lac-repressor

If we use our main stream science hats, are palindromes thought to be some kind of mutations?

My answer is that we can think of such interacting systems as being Irreducibly Complex (IC) as each one needs the other in order to work.

See for example the next figure:

"This arrangement of two identical sequences of base pairs running in opposite directions is called an inverted repeat."

So, truncated palindromic fragments are called inverted repeats. Let's see the CAP binding region in context:
A close-up of the "inverted repeats" (highlighted in bold) is:

acactcaatcgagtga

"The strategy illustrated by CAP and its binding site has turned out to be used widely. As more and more DNA-regulating proteins have been discovered, many turn out to share the traits we find in CAP"

Let's see the protein itself:

The recognition helices of each polypeptide of CAP are, of course, identical. But their orientation in the dimer is such that the sequence of bases they recognize must run in the opposite direction for each recognition helix to bind properly."

"...the traits we find in CAP:
1) They usually contain two subunits. Therefore, they are dimers.
2) They recognize and bind to DNA sequences with inverted repeats.
3) In prokaryotes, recognition and binding to a particular sequence of DNA is accomplished by a segment of alpha helix. Hence these proteins are often described as helix-turn-helix proteins."

"CAP consists of two identical polypeptides (hence it is a homodimer). Toward the C-terminal, each has two regions of alpha helix with a sharp bend between them. The longer of these is called the recognition helix because it is responsible for recognizing and binding to a particular sequence of bases in DNA.

The graphic shows a model of CAP. The two monomers are identical. Each monomer recognizes a sequence of nucleotides in DNA by means of the region of alpha helix labeled F. Note that the two recognition helices are spaced 34Å apart, which is the distance that it takes the DNA molecule (on the left) to make precisely one complete turn."

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Notes:

1-

The status of the paper by Dr Voie has changed from In Press to:

Biological function and the genetic code are interdependent
Øyvind Albert Voie
Chaos, Solitons & Fractals
Volume 28, Issue 4 , May 2006, Pages 1000-1004.

2- More personal correspondence related to my Palindromati article can be seen next:

a)

"It was my belief that Genbank filters submitted data to identify linker sequences and other 'clutter'.

Your abstract indicates that either this is not the case anymore or that Genbank does a rather sloppy job.

Because of their intrinsic nature (Being linkers containing at least one common restriction site and used in libraries), such sequences cannot have ORF stop codons, thus, are predetermined for ORF continuation in concatenated sequences.

In other words, heterotranscripts (normally) escape being spotted in laboratory settings (they should, however, trigger a flag if scientists would more often run sequence analysis software (such as BLAST), or would interpret multiple transcripts in Northern analysis more carefully).

By the way, my first clone isolated here at _____ was a chimeric cDNA!"

b)

"Your manuscript on hetero trans-splicing between chromosomes is very interesting."

c)

"Your new work on heterotranscripts of mRNA sounds VERY interesting."

d)

"I think the topic of trans-splicing sounds fascinating.

Perhaps large scale analysis of deposited ESTs and other transcripts may shed more light into this phenomenon, as the current SAGE tags would seem to me too short to easily observe trans-splicing events, or to reliably indicate trans-splicing enhancer sequences. At any rate, I think this is certainly worth pursuing and I wish you the best of luck.

Although I do not have the resources to devote more time to this topic at the moment, I would be happy to keep in touch as you pursue your research."

My answer to the last researcher was the next one:

"With thousands of mRNA sequences, we can now identify their ways of assembly.

When using “Affymetrix oligo-arrays”, I find that almost all the mRNAs have a specific pattern in which five or so, of the sixteen fragments with 25 bases in length are the ones that make the “peak(s)” of intensity, and those patterns are conserved even in different tissues.

As you know, the first report of Trans-Splicing in humans showed a “naturally” occurring palindromic linker (CCGAATTCGG) which being originated from an unknown location in the genome, tied information from two chromosomes, 1 and 7.

It doesn’t need to be necessarily a palindromic sequence, but because of the novelty of the first report I decided to explore the natural presence of linkers in mRNA sequences.

Other significant sequences in the Trans-Splicing process are enhancers of that mechanism, i.e., GAAGAAG and GAGGAGGAGGG, to name a few.

In reviewing ___ supplementary material (Nature Genet. 23:387-8, 1999) the study of sequences reported (i.e. CCTGTAATCC and GTGAAACCCC) gives me reason to continue my research.

I think that the experiments are not going to be so expensive in the first stage, because basically is to selectively pick up the mRNAs that respond to that probe from different tissues, to sequence them and to report them.

P.S. Also from the most repetitive sequences ____ in ____ 1999 Nat. Genet. Letter until now in my search I can see that amazingly that sequences are only present in humans, it seems that some signaling of specificity are they giving..."