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Programmable Memory in Prokaryotes

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prokaryote

In the past couple of days (here and here), we’ve documented upsets in conventional evolutionary thinking. Here’s a third. Three strikes and you’re out?

Excitement over the CRISPR-Cas9 gene-editing tool has led to more research on how the system works in bacteria, from where it was plagiarized by human geneticists. Science Magazine now says that it appears to provide adaptive immunity to prokaryotes. Most interesting is how the system works. Again, we will need to read past the evo-speak to understand what’s really going on:

The arms race between prokaryotes and their perpetually evolving predators has fueled the evolution of a defense arsenal. The so-called CRISPR-Cas systems — clustered regularly interspaced short palindromic repeats and associated proteins — are adaptive immune defense systems found in bacteria and archaea. The recent exponential growth of research in the CRISPR field has led to the discovery of a diverse range of CRISPR-Cas systems and insight into their defense functions. These systems are divided into two major classes and six types. Each system consists of two components: a locus for memory storage (the CRISPR array) and cas genes that encode the machinery driving immunity. Information stored within CRISPR arrays is used to direct the sequence-specific destruction of invading genetic elements, including viruses and plasmids. As such, all CRISPR-Cas immune systems are reliant on the formation of CRISPR memories, known as spacers, to facilitate future defense. To form these memories, small fragments of invader nucleic acids are added as spacers to the CRISPR memory banks in a process termed CRISPR adaptation. The genetic basis of immunity means that CRISPR adaptation provides heritable benefits, an attribute that is unparalleled in eukaryotic immune systems. There is widespread evidence of highly active CRISPR adaptation in nature, and it is clear that these systems play important roles in shaping microbial evolution and global ecological networks.

Think of it: a “simple” bacterium can identify a foreign invader, capture part of its genetic sequence, and store it in a memory bank. The article goes on to say that it uses a kind of last-in-first-out algorithm, placing the most recent sequence at the active end. Moreover, the enzymes monitoring the database are able to determine if the invader is entirely new or a mutated version of a previous attacker.

Here’s a small taste of the article to savor the design implications:

Before integration, accurate processing of the spacer precursors is required to ensure that the new spacers are compatible with the protein machinery in order to elicit CRISPR-Cas defense. For a given CRISPR-Cas system, spacers must typically be of a certain length and be inserted into the CRISPR in a specific orientation. It is becoming increasingly apparent that Cas1-Cas2 complexes from diverse systems are capable of ensuring that these system-specific factors are met with high fidelity.

Would anyone have expected such sophistication in the smallest, supposedly most primitive forms of life? This has the hallmarks of precision anti-hacking software. In modern computers, antivirus programs store sequences of known viruses to be able to distinguish friend from foe. Can blind processes of nature do this?

Think about it; a mechanism for storing alien sequences would be useless without the recognition and response system. But recognition and response would be useless without the ability to store the alien sequences with high fidelity, in the right orientation, in the right length, in the right order.

Here’s more:

New findings also account for the ordering of stored memories: Typically, the insertion of new spacers is directed to one end of CRISPR arrays, and it has been shown that this enhances immunity against recently encountered invaders. The chronological ordering of new spacers has enabled insights into the temporal dynamics of interactions between hosts and invaders that are constantly changing. Some CRISPR-Cas systems use existing spacers to recognize previously encountered elements and promote the formation of new CRISPR memories, a process known as primed CRISPR adaptation. Viruses and plasmids that have escaped previous CRISPR-Cas defenses through genetic mutations trigger primed CRISPR adaptation. Several recent studies have revealed that primed CRISPR adaptation is also strongly promoted by recurrent invaders, even in the absence of escape mutations. This has led to previously separate paradigms of invader destruction and primed CRISPR adaptation beginning to converge into a unified model.

As noted, in three days we’ve observed three genetic mechanisms that destroy the Central Dogma, fail to confirm neo-Darwinism mutation/selection expectations, and undermine the Tree of Life itself.

If an octopus can edit its own RNA and prevent neo-Darwinism, it is not becoming more fit; it is fit and always has been. If a virus can be almost as complex as a cell but gain its complexity by theft of existing parts, it is not a stepping-stone to the first cell. And if bacteria can operate a complex adaptive immune system using stored memories and active response systems, they do not deserve the epithet “primitive” nor a lowly position in the hierarchy of living things.

We may need to cast off Darwinian metaphors to understand life. The language of an “arms race” or “evolutionary strategy” or “tree of life” tends to obscure understanding, not enlighten it. If Darwinian evolution doesn’t work, why maintain the icons of Zombie Science it entails?

A design perspective would expect cooperation, homeostasis, and programmed adaptability using very complex, interacting parts. These three discoveries fit that picture well.

Photo: “Three strikes, you’re out,” via Wikicommons.