Fuzzy Meaning

Sometimes it’s good to revisit a paper I read a while back but did not appreciate. For today’s post, that paper is “The Meaning of Biological Information” (Koonin, E. V. Phil. Trans. R. Soc. A 374: 20150065, DOI: 10.1098/rsta.2015.0065). It’s not earth-shattering, but it more than meets the eye on my second read.

 

Koonin first distinguishes coming up with an equation to calculate information from the one used to calculate Shannon entropy. Then he (correctly in my opinion) emphasizes that what constitutes information is in the eye of the beholder. Where is this information stored? The genome. No surprises there. I’d argue it’s not just the genome but the entire cell, but that’s a discussion for another day. What type of information does the genome store? What does biology want to behold? Koonin says “information about the environment, allowing the organism to predict and exploit environmental changes”. I say Amen. He goes on to say “another key part is about the (nearly) universal aspects of cellular and organismal design”. Okay, I say. But I’d say the cell is responsible for this although the genome plays a tightly coupled role in the business of living.

 

The next important observation Koonin makes is that animals and plants, the so-called ‘higher-complexity’ organisms have “the highest total information content but are also entropic genomes with a low biological information density”. Thus, prokaryotes are more information-dense. They have to be because selection is stringent for survival if you’re a bacterium or archaeum. Complex multicellular organisms on the other hand are only subject to “weak purifying selection and the high intensity of genetic drift preclude efficient purging of meaningless sequences and conversely allow proliferation of such sequence, in particular, various mobile elements”. But meaning is also in the eye of the beholder, and the question is what these mobile elements represent.

 

Koonin is going to endow such sequences with “fuzzy meaning”. Why are they fuzzy? These elements in the genome can be endowed with meaning at some point down the road evolutionary as they are transcribed. And some of them certainly are, not to make a distinct protein, but as some sort of regulatory element. This is where my limited knowledge of biochemistry hinders me from a fuller understanding. I know regulation is crucial in the living cells of extant life but I can’t quite comprehend its dizzying complexity – wheels within wheels turning every which way. Koonin helps clarify why these mobile elements might be important: “the sequences with fuzzy meaning form the material basis of plasticity from which functional molecules, primarily but not exclusively, regulators of various processes, are continuously recruited to assume better meaning.” And if you need information about changing environments around you to survive or thrive, the fitter organisms will have some plasticity as their back pocket ace.

 

What we thought of previously as junk DNA isn’t quite junk. But neither do we know exactly what it is for. It has the potential to be a useful adaptation. One example Koonin gives: “genes from selfish elements are often recruited by host organisms such that the specific activity of the encoded protein is modified and appropriated for host function”. The example I’m thinking about is how organisms coopt a poisonous molecule into a messenger molecule over time. That’s a big chunk of secondary metabolism in plants and insects, and likely many other organisms. There’s an arms race with different species employing poisons and protections. Many of the molecules we hear about that are chemically poisonous are found naturally in our body: cyanides, peroxides, hydrogen sulfide, and more. Koonin’s arguments make more sense to me now that I understand a bit more biochemistry, having forced myself to teach it last year.

 

To calculate information or ‘meaning’ in a genome, Koonin defines it as calculating the differences that could arise by comparing “an alignment of homologous sequences”. Thus, information density is relative, not absolute. I’ve been struggling to think about how to export this idea to the prebiotic molecules that I study. This is pre-genome so there’s nothing to align. But perhaps the (closed) autocatalytic set is analogous to the genome. Certainly we’d want to catalog the identities of the molecules and look at their diversity. But we’d also likely need an analog component to track concentrations of each molecule. I haven’t quite wrapped my mind around how to do this yet. It’s still fuzzy for me. And perhaps fuzzy meaning is the appropriate term to use here.