Reasons to Believe

Biochemical Synonyms Optimized, Part 1 of 2

New Study Uncovers More Evidence for Biochemical Optimization and Intelligent Design

Most people who do a lot of writing find a thesaurus a valuable resource. Having a list of synonyms handy helps writers carefully choose the best word, making their writing more exact. It also helps them avoid using the same word over and over again.

As helpful as a thesaurus might be, it can cause problems if not properly used. Synonyms are not always interchangeable, and if little thought is given to synonym selection, a nonsensical sentence can result.

Synonyms are not exclusive to human languages. They are also part of the biochemical information systems of the cell. (Go here for an article on biochemical information.) “Biochemical synonyms” (also called codons) are an integral part of the genetic code, the set of rules that define the cell’s information systems. The cell’s machinery uses these rules to produce proteins from the information stored in DNA.

In recent years, biochemists have discovered that these biochemical synonyms (codons) are not completely interchangeable, like some synonyms in the English language. (For example, go here for a technical article that illustrates this newly recognized phenomenon.) It turns out that some codons are better suited than others for producing functional proteins. Biochemists refer to these preferred biochemical synonyms as optimal codons.

A new study demonstrates that the usage of such codons appears to be optimized, providing added evidence that life stems from the work of a Creator. This week I will present the background information necessary to appreciate this new insight (or understanding, if you consult a thesaurus). A good place to start is with proteins.

Proteins

This class of biochemicals serves as the “workhorse” molecules of life, taking part in essentially every cellular and extracellular structure and activity. These compounds help form structures inside the cell and in the cell’s surrounding matrix. Among other roles, proteins catalyze chemical reactions, harvest chemical energy, participate in the cell’s defense systems and store and transport molecules.

Proteins are chain-like molecules that fold into precise three-dimensional structures. The protein’s three-dimensional architecture determines the way it interacts with other proteins to form larger complexes. The structure of the folded protein dictates its function.

Proteins form when the cellular machinery links together (in a head-to-tail fashion) smaller subunit molecules called amino acids. The cell employs twenty different amino acids to make proteins. The amino acids that make up the cell’s protein chains possess a variety of chemical and physical properties. In principle, amino acids can link up in any of the possible amino acid combinations and sequences to form a protein.

Each amino acid sequence imparts the protein chain with a unique chemical and physical profile along its chain. As amino acids along the length of the chain attract and repel each other, the chemical and physical profile determines how the protein chain folds. Because structure determines the function of a protein, the amino acid sequence ultimately defines the type of work the protein performs.

Not all the amino acids in a protein chain are equal. Some are critical residues, meaning that if they are replaced by another amino acid, the protein chain will not properly fold and will lose function. Others can be substituted with little consequence to the protein’s structure and function. Biochemists refer to these amino acids as variable.

DNA

Like proteins, DNA consists of chain-like molecules known as polynucleotides. Two polynucleotide chains align in an antiparallel fashion to form a DNA molecule. (The two strands are arranged parallel to one another with the starting point of one strand located next to the ending point of the other strand, and vice versa.) The paired polynucleotide chains twist around each other forming the well-known DNA double helix. The cell’s machinery forms polynucleotide chains by linking together four different subunit molecules called nucleotides. The four nucleotides used to build DNA chains are adenosine, guanosine, cytidine, and thymidine, familiarly known as A, G, C, and T, respectively.

DNA stores the information necessary to make all the proteins used by the cell. The sequence of nucleotides in the DNA strands specifies the sequence of amino acids in protein chains. Scientists refer to the amino-acid-coding nucleotide sequence (for constructing proteins) as a gene. Through the use of genes, DNA stores the information functionally expressed in the amino acid sequences of protein chains.

The Genetic Code

At first glance, there appears to be a mismatch between the storage and functional expression of information in the cell. A one-to-one relationship cannot exist between the four different nucleotides of DNA and the twenty different amino acids used to assemble proteins. The cell overcomes this mismatch by using a code comprised of groupings of three nucleotides, called codons, to specify the twenty different amino acids.

The cell uses a set of rules to relate these nucleotide triplet sequences to the twenty amino acids comprise proteins. Molecular biologists refer to this set of rules as the genetic code. The nucleotide triplets represent the fundamental units of the genetic code. The genetic code uses each combination of nucleotide triplets to signify an amino acid. This code is essentially universal among all living organisms.

Sixty-four codons make up the genetic code. Because the genetic code only needs to encode twenty amino acids, some of the codons are redundant. That is, different codons code for the same amino acid. In fact, up to six different codons specify some amino acids. Other amino acids are specified by only one codon.

As I discussed in my book The Cell’s Design, the rules of the genetic code and the nature of the redundancy appear to be designed to minimize errors in translating information from DNA into proteins that would occur due to substitution mutations. This optimization stands as evidence for the work of an Intelligent Agent.

Mutations

A mutation refers to any change that takes place in the DNA nucleotide sequence. DNA can experience several different types of mutations. Substitution mutations are one common type. When a substitution mutation occurs, one (or more) of the nucleotides in the DNA strand is replaced by another nucleotide. For example, an A may be replaced by a G, or a C may be replaced by a T. This substitution changes the codon that the nucleotide takes part in. Interestingly, the genetic code is structured in such a way so that when substitution mutations take place, the resulting codon specifies the same amino acid (due to redundancy) or an amino acid that has similar chemical and physical properties to the amino acid originally encoded. This cleverly orchestrated relationship further evinces Intelligent Design.

When substitution mutations generate a new codon that specifies the same amino acid as initially encoded, it’s referred to as a synonymous mutation. When a substitution, however, produces a codon that specifies a different amino acid, it’s called a nonsynonymous mutation.

Nonsynonymous mutations can be deleterious if they affect a critical amino acid or if they significantly alter the chemical and physical profile along the protein chain. If the substituted amino acid possesses dramatically different physicochemical properties from the native amino acid, the protein folds improperly. This improper folding impacts the protein, yielding a biomolecule with reduced or even lost function.

Synonymous Mutations are not Interchangeable

Biochemists used to think that synonymous mutations had no impact whatsoever on protein structure, and hence function, since the amino acid sequence specified by the synonymous change would be identical.

Recently, biochemists have recognized that their perception about synonymous changes was wrong. Even though the amino acid sequence hasn’t changed, the protein structure can be altered. One hypothesis involves the speed with which the cell’s machinery reads the information used to direct the production of the protein chain. Some codons are read faster by the cell’s machinery than others. And this reading rate affects the production speed of the protein chain. When proteins are produced they are put together in an assembly line-like fashion, with one amino acid added at a time. As the protein chain is assembled, it starts to fold before it’s built in its entirety. And the folding pattern will change depending upon the pace of the protein’s construction.

Another explanation has to do with the tendency of the cell’s machinery to make mistakes when reading codons. Some codons that are part of a synonymous codon list are more likely to be misread than others. So even though the information needed to make a particular protein hasn’t changed, the wrong amino acid still may be introduced into the protein chain because of the codon used. This error, of course, can lead to structural and functional abnormalities in that protein, just as if a nonsynonymous change had occurred.

This recent insight about the nonequivalency of synonymous mutations set the stage for biochemists to discover that the usage of the optimal codons is, indeed, optimal.

I’ve gone on long enough for now. Or to say it another way, I’ll save the rest of the discussion for next week, when I will describe this research and discuss its implications.


Part 1 | Part2

Subjects: Biochemical Design, TCM - Biochemical Design

Dr. Fazale Rana

In 1999, I left my position in R&D at a Fortune 500 company to join Reasons to Believe because I felt the most important thing I could do as a scientist is to communicate to skeptics and believers alike the powerful scientific evidence—evidence that is being uncovered day after day—for God’s existence and the reliability of Scripture. Read more about Dr. Fazale Rana