Genomic Tricks

 Targeted Variability


 

Cone Snails

It may have a pretty shell, but don’t pick it up! It may contain a live snail with a deadly cocktail of poisons, delivered by a harpoon-like mechanism. What is most peculiar about these organisms is the number of different toxins they contain. Each of the 500 species of cone snails has at least 50 toxins, and some have as many as 200! - Now that’s overkill. But how does natural selection explain such a feature? You would think that after a dozen or so poisons, there is no selective advantage in producing any more.

 

 

Molecular neurobiologist Baldomero Olivera compared the DNA sequences of the different species of cone snails and found that mutation is not random. One particular segment of the genome involved in producing the toxins has an unusually high mutation rate. This region also experiences the loss and gain of small patches of DNA. Mutability somehow favors a specific region of DNA in these organisms.


 

Adaptive Immunity

Cone snails are not the only example of targeted variability. We humans perform a procedure of focused mutability in certain cells of the adaptive immune system. At a specific stage of development the T and B lymphocyte precursors undergo a programmed gene re-arrangement process which is partially ordered and partially random. This generates the diverse array of antibodies needed to attack invaders of the body.


 

Spirochete Coats

Another example of targeted variability is the spirochete bacteria that have an external coat that frequently changes to avoid detection by the adaptive immune system of the host. The spirochete changes its coat by inserting new patches of DNA into the gene that codes for its coat protein. With its library of extra pieces of DNA on hand the spirochete can generate an incredible number of different coat proteins.
Investigators interested in the mechanism of this evasive technique have examined the protein sequences of many spirochete bacteria and have found a conserved region that repeats with the same five amino acids. Now this is where it gets interesting. If you look at the DNA sequence that codes for this string of amino acids, it is always the same string of nucleotides - in all of the repeats, and in all of the bacteria tested. Now if you know how the genetic code is arranged - with a triplet of the four nucleotides in DNA coding for one out of a possible 20 amino acids (21 if you count selenocysteine) - then you know that code is degenerate. There are 64 possible triplet sequences of the four nucleotides, so there is often more than one combination coding for the same amino acid. The codons that code for the same amino acid are called synonymous codons. A point mutation often changes one synonymous codon for another with no consequence whatsoever in the protein produced. Now there are many different fifteen nucleotide sequences that will code for this particular string of five amino acids in the spirochete genome, in fact nearly 200. But they never appear!
The simplest conclusion to draw from all of this is that there is ->


 Another Code


 

This specific DNA sequence within the gene that is not at all related to the triplet code that encodes for amino acids is apparently dictating a DNA or RNA behavior!



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