James A. Shapiro: Can Cells Bias Natural Genetic Engineering Toward Useful Evolutionary Outcomes?

A few blogs ago I asked, “Where, in fact, do ‘the good ones’ really come from?” By “good ones” I meant useful genome changes in evolution. This question stimulated some debate about whether it was possible to distinguish good changes from bad changes before they occur.

In the abstract, this may seem an overwhelmingly difficult problem. But if we think a bit about the highly organized state of the genome and non-random natural genetic engineering, biasing changes toward “good ones” becomes more conceivable.

I have already discussed purposeful, targeted changes in the immune system. The immune system illustrates how efficiently cells can target DNA restructuring by recognizing specific sequences and coupling DNA changes to transcription (copying DNA sequence into RNA).

Some evolutionists object that a somatic process like antibody synthesis provides no model for germline changes in evolution. So let’s examine natural genetic engineering events in microbial cells. We’ll look at mobile genetic elements targeted in ways that increase their evolutionary potential.

Mobile genetic elements come in many forms. Some operate purely as DNA. Others make an RNA copy and reverse transcribe it back into DNA as it inserts at a new location. Elements that move, or transpose, to multiple new locations are called “transposons” or “retrotransposons” (if they use an RNA intermediate).

Other mobile elements only insert in particular locations by a process called “site-specific” recombination. In bacterial evolution, this process is used in specialized structures called “integrons” that capture casettes containing protein coding sequences for antibiotic resistance, pathogenicity, and other functions.

What all mobile elements share are proteins that aid them to cut and splice DNA chains so that they can construct novel sequences, much as human genetic engineers do in their test tubes. These proteins have various names, such as “recombinase,” “transposase,” and “integrase.” It is the specificity of the cutting reactions involving these proteins that determines where a mobile element moves in the genome.

One fascinating case of highly biased integration is the bacterial transposon Tn7. Tn7 has two specialized proteins to target its transposition. The TnsD protein directs Tn7 to insert into a special “attTn7” site in the chromosomes of many bacterial species where it does not disrupt any host functions and so causes no deleterious effects.

Another, more interesting protein, TnsE, directs Tn7 to insert into replicating DNA molecules. The reason this is important is that transmissible plasmids replicate their DNA as they transfer from one cell to another. TnsE targeting to plasmids in transit to new cells thus enhances the spread of Tn7 and the resistances it carries to many different kinds of bacteria.

Tn7 carries its antibiotic resistance determinants in an integron. Integrons and their recombinase proteins are likewise specialized to participate in plasmid spreading through bacterial populations. Plasmids enter new cells as single-stranded DNA. We learned just in 2005 that integron site-specific recombinases are special in operating on single-stranded DNA, not double-stranded molecules like previously studied recombinases. Moreover, integron recombinase synthesis is triggered by the entrance of single-stranded DNA into a cell. So integron activity is intimately linked in more than one way to plasmid transfer.

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James A. Shapiro: Can Cells Bias Natural Genetic Engineering Toward Useful Evolutionary Outcomes?

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