Some Assembly Required

Some Assembly Required is the title of Neil Shubin’s latest book. Its scope is ambitious; the book is subtitled “Decoding Four Billion Years of Life, from Ancient Fossils to DNA”. I find the cover art simple yet mesmerizing. As a chemist who studies the origin-of-life, the book’s title aptly describes my field – some (molecular) assembly is required indeed. Shubin is not a chemist, rather he combines paleontology and molecular biology in his research. He is famous for his work on Tiktaalik, well-chronicled in his delightful book Your Inner Fish. 

 

Some Assembly Required is about the seemingly large-scale adaptations in biological and organismal evolution that look like miraculous jumps. But the miracle lies on the molecular and cellular level. When you look both deeper and smaller, the story becomes very interesting. Our cells are molecular chop shops: using, adapting, and repurposing molecular structures to achieve all manner of tasks. Some of the instructions are baked into the DNA, but a host of molecular regulation controls what shows up when.

 

Today’s blog post highlights Chapter 5: Copycats. First, I’ll quote a paragraph from Shubin, so you have a taste of his marvelous prose.

 

The genome at every level resembles a musical score in which the same musical phrases are repeated in different ways to make vastly different songs. In fact, if nature were a composer, she would be one of the greatest copyright violators in history – everything, from parts of DNA to entire genes and proteins, is a modified copy of something else. Observing duplications in the genome is like wearing a new pair of glasses: the world looks different. Once you see duplications in the genome, you see them everywhere. New genetic material looks like copies of old stuff that was repurposed for new uses. The creative power of evolution is more like a copycat who duplicates and modifies ancient DNA, proteins, and even the blueprints that build organs, for billions of years.

 

Three protagonists grace the chapter. The first is Susumu Ohno, who apparently has “made a hobby of translating the structure of proteins into concert pieces for violin and piano” although he was a maestro of studying chromosomes in the 1960s. Looking closely at the staining patterns of light and dark bands, Ohno realized that the genome was full of duplicated genes. Over and over and over again. I was also impressed reading about Ohno’s low-tech proxy of figuring out how much genetic material different organisms had. He carefully and painstakingly made paper cutouts of his chromosome pictures… and weighed them! While I did not know about Ohno until reading Shubin’s book, I had heard of Roy Britten and Barbara McClintock, and their contributions to understanding the strange tale of genes duplicating themselves and jumping around the genome.

 

Reading the chapter made me think of the similarities of duplicating jumping stretches of DNA and the chemistry of autocatalysis. An autocatalytic cycle is set up when an intermediate or product in a chemical reaction enhances an increase in one of its precursors. A frenzy of duplication takes place leading to autocatalytic growth. At some point, this comes to a halt when all the starting material is used up. But what if you had two catalytic cycles? One produces the reactants the other needs and vice-versa. Cross-catalysis could lead not only to the sustenance of such cycles, but to growing new appendages – new sub-cycles that eventually lead to a vast complicated system. Life is like that. No man is an island. I am constantly exchanging molecules with the environment to stay alive, taking in oxygen and breathing out carbon dioxide being two prime examples. Photosynthetic organisms do the opposite exchange.

 

One seemingly odd feature of life is that it uses only a very small subset of molecules in biology. As a chemist, this is intriguing. Why doesn’t life utilize the brothers, sisters, cousins, nephews, nieces, that are structurally closely related? When the chemist tries to make a biomolecule from simpler molecules in a plausibly prebiotic way (i.e. no fancy reagents or catalysts that might not have existed at the dawn of life), we get an “embarrassment of riches” – the whole extended family. Why does life pick out just a few characters to star in its drama?

 

I think the copycat idea applies deep down at the chemical level when paired with autocatalysis. Chemical evolution is, perhaps at a fundamental level, not so different from biological evolution. The chop-shop is at a different level, but it functions in the same way: use, re-use, adapt, re-purpose. What is the fundamental driving force for this behavior? As I tell my students in G-Chem 1, chemistry is all about energy. When we get to G-Chem 2, entropy and energy dissipation will come into play. But we don’t get to its heart: non-equilibrium thermodynamics. I don’t even go there in P-Chem. Perhaps I should. Some assembly will be required. But maybe I should first go out and see what I can copy, use and re-purpose. That’s what life does.