Lame Science #11: Insights into the Origins of Life Facilitated by Computer Models

The origins of life (OOL) is one of most perplexing, speculative, and controversial topics in all of biology, but it has always been one of my favorite issues to read about, discuss, and even debate. There are a variety of OOL scenarios hypothesized by researchers, each of which is fraught with its own specific and particular set of difficulties. Most people that have taken a biology class are familiar with the Miller-Urey experiment, wherein what was at the time believed to be the Earth’s early atmosphere was simulated, electricity pulsed through the “primordial atmosphere,” and the resulting compounds were analyzed. Produced in the experiment were a variety of biologically relevant compounds, including some of the alpha amino acids used in biological systems.

Considered to the be the quintessential OOL experiment, Miller-Urey initiated more than 60 years of research into the chemical origins of life, also known as abiogenesis. Any given abiogenesis scenario will have to account for a number of specific things in order to address the question adequately. These include, but are not necessarily limited to:

  • Origins of Organic molecules, including their synthesis, inhibition of catalysis, and the origins of homochirality. In other words, where did the organic chemicals necessary for life come from, how was their breakdown inhibited, and how did molecules with the proper stereochemistry come together following synthesis?
  • Sequestration or Enclosing of the Protocell
  • Replication or Duplication of the Protocell
  • The Origins of Biological Information
  • The Origins of Biological Metabolism

A recent article, published in PLOS One and titled The natural history of molecular functions inferred from an extensive phylogenomic analysis of gene ontology data, is reported by ScienceDaily as shedding “light on origins of life on Earth through molecular function,” though in reality the article does nothing of the sort.

Since competing OOL scenarios can’t all be correct–they are in fact, in competition among one another for the best of the worst ideas–OOL researchers tend to spend a good deal of time criticizing other models.

Let’s face it, when you’re ideas are made up–even if based off of some reasonable speculation or hypothesis–one scenario no more likely to true than another, and when it comes down to it, there will never be a definitive answer reached with respect to this question.

When I was in graduate school for molecular biology, the en vogue OOL theory was the so-called RNA world. To make a long and detailed story somewhat brief: RNA is unique among biological molecules in that it can retain and transmit biological information, but also possesses some degree of catalytic activity. The long and short of it is that the RNA world hypothesis was attractive because it addressed two issues: biological information and catalytic activity with one molecule.

In other words, the RNA world hypothesis solved two potential problems how is information retained and transmitted, and how are these reactions catalyzed. Since RNA retains information and can catalyze its own synthesis, using its specific sequence as a template, the hypothesis gained relatively wide acceptance.

While not specifically mentioned in the research article linked above, the ScienceDaily article details some of the difficulties with the RNA world hypothesis:

Some scientists refute this idea, however, saying RNA is too large and complex a molecule to have started it all. That group says simpler molecules had to evolve the ability to perform metabolic functions before macromolecules such as RNA could be built. This idea is appropriately named “metabolism-first,” and new evidence out of the University of Illinois backs it up.

Stating that RNA is too large and complex is extremely understated, and doesn’t give an accurate picture of the true scope of difficulties with the RNA world hypothesis.

A similar analogy might be characterizing a friend’s upcoming trip to Yemen, wherein they’ll be wearing only clothing that has representations of the American flag, as “unwise.”

Nonetheless, the hypothesis put forward in this article–metabolism first–competes with the RNA world hypothesis. The idea is that in order of many if not most of the necessary components of life to come together, some sort of crude metabolic activity must have existed to supply these molecules, hence, metabolism first.

In order to address this question, the research team took a broad, zoomed out perspective on proteins, the working molecules of biological systems, and used database, the Gene Ontology database (GO), that groups proteins together based on their specific known functions. Within the GO database, data for 249 organisms, containing representatives from archea, prokaryotes, and eukaryotes were available for comparison.

Computer modeling analyzed the proteins functions, determined in which organisms they were present, and found that eight broad categories of activity emerged:

  • Catalytic activity
  • Binding
  • Transporter activity
  • Molecular transducer activity
  • Protein binding transcription factor activity
  • Antioxidant activity
  • Electron carrier activity
  • Enzyme regulator activity

These data are shown in Figure 1 below. The eight biological activities listed above are represented by the red “8” in the Venn Diagram of Figure 1. These data show that these activities are common to all three domains of life. In contrast, the green “4” represents activities found in prokaryotes and eukaryotes, but not archaea, and the black 5 represents activities found in eukaryotes only.

Figure 1. Distribution and evolution of metabolic activities as determined by computer modeling and grouping of protein function.

According to the authors, the number of times a function appears in a genome provides information about the evolutionary history of life. Based on this notion is that an ancient function will be shared by all organisms and will be found more frequently relative to more recently evolved metabolic activities, which will appear less frequently, and in fewer organisms.

The authors report that the earliest functions to evolve those related to metabolism and binding, followed by molecules that were able to synthesize large organic molecules, integration of these molecules into cells, cell-cell communication, and then finally, functions related to development of sophisticated and highly differentiated organisms, such as animals.

While I have no doubt that the authors statistical methods and computer models are sound, I submit that 1. This research does NOTHING to shed any light on the OOL, and 2. The entire basis of the research is fundamentally flawed.

While the paper is long, well-written, and contains a large amount of data and analysis, it essentially tells us this: We believe metabolism evolved first, and that some metabolic activities, such as binding and catalytic activity are so essential, they must have evolved first.

Yeah? No kidding.

Ignoring for a moment the “metabolism first” hypothesis, one can speculate with a good degree of assurance that the first metabolic activities to arise would be those that are critical to life. This is no stretch, nor does it require a large amount of critical thinking to understand. There are bound to a be a “core group” of metabolic activities that are essential for cellular life, and these core activities, because they’re essential, are going to be found more frequently.

Coming back to the “metabolism first” hypothesis: This research does not illustrate that metabolism came first. It might show that certain metabolic activities are more common than others, and that in turn implies something about their importance and their evolutionary age, but does NOTHING to elucidate the origins of these pathways.

Consider an analogy: If you were to study the wide variety of bicycles available in the modern world and break them down into functions, map them to different bikes, and construct Venn Diagrams, you would discover that bicycles all possess a core group of components:

  • Frame
  • Wheels
  • Drivetrain
  • Steering
  • Stopping

Most can agree that these are the core functions or components of any bike.

In the overlap between mountain bike and BMX bike, you’ll see that they share a some features, things such as: Knobby tires, reinforced welds, etc. In the overlap between mountain bikes and road bikes you’ll see items such as speedometers, gears, ‘evolved’ braking systems, etc.

Furthermore, I could categorize not only modern bikes, but bikes throughout history and show that all bikes have always had some of these items; that core group is essential. As time progresses and the bike evolves, we see that more features are added, some of them are common in some bikes, gears and disc brakes, for example, and some will be unique to only a certain type of bike, such as tassels on the handlebars of a kids bike.

I could show you that disc brakes evolved much later than rim brakes, and that coaster brakes are limited to only very specific categories of bikes. I could show you that banana seats are extremely rare and never found among racing bikes or downhill bikes.

While all of this information is might be interesting, and perhaps even useful, it says nothing about the origins of bicycles, and it most certainly doesn’t imply what models of bikes existed before the currently existing models. None of this shows that bizarre contraptions that preceded the modern bike. If we didn’t know that bikes in the past looked like those in Figure 2 below, would we be able to infer it from the structure and design of the modern bike?

For that matter, based on the structure of the modern bike are we correct to assume that drivetrains were always a necessary component of a bicycle? Sure, all bikes that we have currently possess drivetrains, and based on that, we might speculate that all bikes need to have drivetrains, but it’s entirely possible that the earliest versions of bikes didn’t have drivetrains, and you pushed yourself along with your feet, such as is the case with those bicycles used to train young children.

In short, this paper does nothing to shed any light on the origins of life, nor does it provide support for the metabolism first hypothesis. The best this paper can do is speculate about the evolutionary age of different broad metabolic processes, but doesn’t provide any information about their origins.

Hence, Lame Science.

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