February 9, 2015
From time to time, biochemists make discoveries that change the way we think about how life works. In a recent paper, Ian S. Dunn, a researcher at CytoCure, argues that biomolecules (such as DNA, RNA, and proteins) comprised of “molecular alphabets” (such as nucleotides and amino acids) are a universal requirement for life.1
Dunn’s work has far reaching implications. Perhaps the most significant relates to thecentral dogma of molecular biology (the organizing framework for biochemistry). First proposed by Francis Crick in 1956, the central dogma states that biochemical information flows from DNA through RNA to proteins.
The RNA world hypothesis, a leading evolutionary explanation for life’s origin, supposes that the central dogma of molecular biology is an unintended outcome of chemical evolution. This hypothesis posits that initial biochemistry was built exclusively around RNA and only later did evolutionary processes transform the RNA world into the familiar DNA-protein world of contemporary organisms. Thus, the DNA-protein world is merely an accident, the contingent outcome of evolutionary history.
Origin-of-life researchers claimed support for the RNA world with the discovery ofribozymes in the 1980s. These RNA molecules possess functional capabilities. In other words, RNA not only harbors information like DNA, it also carries out cellular functions like proteins. Researchers presumed that RNA biochemistry’s dual capabilities later apportioned between DNA (information storage) and proteins (function). Origin-of-life researchers often point to RNA’s intermediary role in the central dogma of molecular biology as further evidence for the RNA world hypothesis. In this view, RNA’s reduced role is a vestige of evolutionary history and RNA is viewed as a sort of molecular fossil.
However, if Dunn is correct and molecular alphabets are a universal requirement for life, it follows that the central dogma of molecular biology cannot be an accidental outcome of chemical evolution—a commonplace assumption on the part of many life scientists. Instead, it seems to be more appropriate to view this process as part of the Creator’s well-planned design.
Chemical Complexity and Life
Chemical complexity is a defining feature of life. In fact, the cellular operations fundamental to biology require chemical complexity. According to Dunn, this complexity can be achieved only through a large ensemble of macromolecules, each one carrying out a specific task in the cell. However, the macromolecules must be assembled from molecular alphabets because only molecular alphabets allow for the plethora of combinatorial possibilities needed to give macromolecules the range of structural variability that makes possible the functional diversity required for life.
Proteins help illustrate Dunn’s point regarding combinatorial potential. Built from an alphabet that consists of 20 different amino acids, proteins are the workhorses of life. Each protein carries out a specific role in the cell. A typical protein might consist of 300 amino acids. So, for a protein of that size, the number of possible amino acid sequences is (20)300. Each sequence has the potential to form a distinct structure and, consequently, perform a distinct function. It is impossible to achieve this kind of complexity using small molecules or uniquely specified macromolecules.
Two Types of Molecular Alphabets
Another defining feature of life is its ability to replicate. For a cell to reproduce it must duplicate the information that specifies the functional macromolecules’ alphabet sequences and then pass it on to the daughter cells. Based on this requirement, Dunn identifies a need for primary and secondary molecular alphabets.
Macromolecules comprised of a primary molecular alphabet must be able to replicate themselves. This requirement, however, places constraints on the macromolecules, preventing them from being able to carry out the full range of functional activities needed to support the chemical complexity required for life. A secondary alphabet is needed to overcome this restriction. Specified by the primary alphabet, the secondary alphabet possesses the full range of functional possibilities because it is not constrained by the need to replicate.
DNA harbors the information a cell’s machinery needs to produce proteins and also possesses the ability to replicate. Therefore, DNA’s nucleotide sequence serves as a primary molecular alphabet while proteins’ amino acid sequences comprise a secondary molecular alphabet, enabling proteins to serve as the cell’s workhorse molecules.
Molecular Alphabets and the Central Dogma of Molecular Biology
According to the central dogma of molecular biology, the information stored in DNA is functionally expressed through the amino acid sequence and protein activity. When it is time for the cell’s machinery to produce a particular protein, it copies the appropriate information from the DNA alphabet and produces a molecule calledmessenger RNA (mRNA). Once assembled, mRNA migrates to the ribosome and directs the synthesis of proteins.
In effect, the central dogma embodies the roles assumed by the primary and secondary molecular alphabets. Information in the cell’s primary molecular alphabet (DNA) is constrained by the need to replicate and so specifies the production of the cell’s secondary molecular alphabet (proteins) with the maximal amount of functional diversity. The translation from primary to secondary alphabet requires a decoding apparatus, which in the cell is comprised of RNA and ribosomes.
The key point is that the central dogma appears to be a fundamental requirement for life—a universal property, a necessary embodiment of life’s requisite chemical complexity. In this sense, it is reasonable to view the central dogma of molecular biology as part of the elegant, sophisticated, well-designed processes characteristic of biochemistry. Conversely, the central dogma of molecular biology can no longer be viewed as an accidental outcome of chemical evolution.
Undermining the RNA World Hypothesis
In the RNA world, the molecular alphabet that comprises RNA is a primary alphabet. But based on Dunn’s work, RNA would also have been constrained in its range of functional capabilities because of its need to replicate. Because of this restriction, the ribozymes of the RNA world cannot provide the chemical complexity necessary to sustain life. Dunn’s insight into the universal character of molecular alphabets unwittingly undercuts the RNA world scenario. Thus, it seems the central dogma of molecular biology (from DNA to RNA to proteins) had to be in place at the point that life originated.
Subjects: Biochemical Design
- Ian S. Dunn, “Are Molecular Alphabets Universal Enabling Factors for the Evolution of Complex Life?,” Origins of Life and Evolution of Biospheres 43 (December 2013): 445–64.