Wednesday, March 31, 2021

Oh, Phosphorus. How art thou?

I'm bored with spinning, TV and reading my books. It's cold and raining outside. So I'm reading a few papers on how phosphates evolved to facilitate biological life. Physics, chemistry and information theory. 

The word phosphorus derives from the Greek phōsphoros: phōs ‘light’ + -phoros ‘-bringing’. Perhaps the Greeks knew more than we do.

I asked this question of my graduate biochemistry instructor: "How did phosphorus evolve to be the key element of life?". She just shook her head and answered, "You just have to sometimes accept that we don't have the answers, that we just don't know."

"Nah. I bet we do, or will soon."

That was in the mid-1980's. Westheimer published a paper, "Why nature chose phosphates", in 1987 proposing a theory (partly) answering my question. His theory was refined in 2013 by Kamerlin, et al: "Why nature really chose phosphates." Then, Liu et al took it to a different level with "How Prebiotic Chemistry and Early Life Chose Phosphate". 

Goldford, et al. commented in the introduction of their paper ("Remnants of an Ancient Metabolism without Phosphate," 2017), "Phosphate is essential for all living systems, serving as a building block of genetic and metabolic machinery. However, it is unclear how phosphate could have assumed these central roles on primordial Earth, given its poor geochemical accessibility." But we now know how phosphates assumed that essential role. 

Hess et al published earlier this year (Nature,16 March 2021) another theory,
"Lightning strikes as a major facilitator of prebiotic phosphorus reduction on early Earth". (Remember the Greeks?) It circles back to biophysicist Werner Loewenstein's 1999 book ("Touchstone of Life") in which he explains why lightening probably facilitated phosphorus being the first and basic element for life on Earth (and may be on other planets). This book is enlightening for integrating information theory, physics, chemistry, and molecular biology. (One star of the book is Maxwell's demon.)

But, wait! A treatise explores the 'phosphorus enigma' at the largest scale: the book, "The Chemical Evolution of Phosphorus: An Interdisciplinary Approach to Astrobiology" (Enrique Maci -Barber, PhD, Professor of Condensed Matter Physics in Madrid, Spain). In the forward of the book, Sun Kwok (astronomer studying the physics and chemistry of stellar evolution) wrote:

"This book beautifully traces the stellar origin of the element phosphorous, its chemical properties, and the observations of phosphorous-based molecules and minerals in the interstellar medium and in the solar system. [The author] then connects the astronomical studies with the role of phosphorous played in living organisms, presenting the biochemistry of biomolecules that incorporate phosphorous, and the roles that these molecules play in the origin of life on Earth."

Unfortunately, the book is also a hefty $150; far out of my price range. 

Branching off but parallel to the road of physics and chemistry, information theory has expanded understanding of prebiotic and current life. My first introduction into this was more like an epiphany while reading Loewenstein's book when it appeared on the shelves in 1999. It filled in the gaps for a continuing passion of concepts in cell signaling. It wasn't just about chemistry; physics was the parent. (College physics, taught only as mechanical physics, turned me off to the subject. I endearing called  it "'fysics; the other 'f' word". Despite that my father, a biophysicist/biochemist, tried to convince me to not ignore 'fysics'.)

Realistically, information theory integrates physics, chemistry, molecular biology, structural biology, geology, and more. It's like a spider web with life (and death) at its core. Whenever anyone, especially during this pandemic, mentions the spike protein and ACE2 receptor, antibodies and ligand, and, especially, the immune system, my immediate response is "Conformation is everything", a mantra I picked up  in biochemistry and incessantly repeat. (Network theory, inclusive of information theory, is now being applied to the immune system.)

Dr. Chris Adami, theoretical physicist and computational biologist, is the one of the few researchers using information theory to understand the physical and medical sciences and evolution. Life should not be thought in terms of chemical events. Instead, it should be thought of as information transmission. Adami comments during an interview:

"Information is the currency of life. One definition of information is the ability to make predictions with a likelihood better than chance. That’s what any living organism needs to be able to do, because if you can do that, you’re surviving at a higher rate... Think of evolution as a process where information is flowing from the environment into the genome. The genome learns more about the environment, and with this information, the genome can make predictions about the state of the environment."

When asked about the origin of life, he relates one of a few hypotheses amongst scientists for the circumstances of life origins: 

"I have heard tremendous amounts of interesting stuff about what happens in volcanic vents [under the ocean]. It seems that this kind of environment is set up to get information for free. It’s always a question in the origins of life, what came first, metabolism or replication. In this case it seems you’re getting metabolism for free. Replication needs energy; you can’t do it without energy. Where does energy come from if you don’t have metabolism? It turns out that at these vents, you get metabolism for free."

 However, nothing is free. Maxwell Demon knows that. The prime denomination of that currency of information is energy. And one of the earliest components of life that transfers energy is a phosphate group in an energy unit: adenosine triphosphate (ATP). With the origin of ATP began the synthesis of large biomolecules. The release of a phosphate group supplies energy for molecular couplings, resulting in adenosine diphosphate (ADP). Subsequent combinations release a phosphate group that reattaches to ADP, forming ATP. This is a positive feedback loop that cycles over and over. 

First there was lightening. Over millions of years of trial and error a system became more stable, and it also became more adaptive. And then life was born.


We have come closer to understanding the origins of life. And I am closer to understanding how and why phosphorus evolved as the key element of life. Did Nature choose this, or did this choose Nature as it's product? That may be an ouroboros question. 

(A comment by Adami echoes thoughts throughout my higher education and academic years: "...the more you learn about different fields, the more you realize these fields aren’t separated by the boundaries people have put upon them, but in fact share enormous commonalities."  Yes.)