Moviegoers in 1982 would have heard this exchange as they watched a team of researchers––draped in sterile white gowns, faces covered in masks––huddle in an operating room around an alien creature, the lovable E.T.
Scientists and laypeople alike equate DNA with life itself. This biomolecule—ideally suited to harbor genetic information—is so indispensable that many in the scientific community find it hard to imagine how any life-form could exist without it.
Yet, in recent years some scientists have begun to question DNA’s exceptional role. These investigators have raised the possibility that maybe life “as we don’t know it” might exist somewhere else in the solar system or beyond. And perhaps such hypothetical organisms don’t have any DNA at all. Instead, they might make use of a completely different type of molecule to store the information needed to direct life’s operations and then pass that information to offspring.
Other scientists are trying to create life in the lab––nonnatural, artificial creatures distinct from anything found in nature. These researchers start with relatively simple molecules and aim to synthesize proto-cellular entities that display the characteristics of life. Investigators have set out on this quest because they hope it will lead to a more fundamental understanding of what life is. Also, the work could yield important biomedical and biotechnology applications. As a first step, some researchers are trying to make artificial DNA molecules.
One of the leaders in this effort is distinguished molecular biologist Steven Benner, who recently formed the Foundation for Applied Molecular Evolution. He and his collaborators have designed a DNA molecule that incorporates eight nonnatural nucleobases into its structure along with the four naturally occurring nucleobases (A, G, C, and T).1 They refer to these artificial DNA molecules as AEGIS (artificially expanded genetic information systems).
DNA
DNA consists of chain-like molecules known as polynucleotides. Two polynucleotide chains align in a parallel fashion to form a DNA molecule. 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, abbreviated A, G, C and T, respectively.
When the two DNA strands align, the adenine (A) side chains of one strand always pair with thymine (T) side chains from the other strand. Likewise, the guanine (G) side chains from one DNA strand always pair with cytosine (C) side chains from the other strand.
Because of the base-pairing rules, if biochemists know the sequence of one DNA strand, they can readily determine the sequence of the other strand. The nucleotide sequences of the two DNA strands that comprise the double helix are said to be complementary to each other.
Nucleotide Structure
The nucleotide molecules that make up the strands of DNA are in turn complex molecules consisting of both a phosphate moiety, and a nucleobase (adenine, guanine, cytosine, or thymine) joined to a 5-carbon sugar (deoxyribose).
The backbone of the DNA strand is formed by repeatedly linking the phosphate group of one nucleotide to the deoxyribose unit of another nucleotide. The nucleobases extend as side chains from the backbone of the DNA molecule and serve as interaction points (like ladder rungs) when the two DNA strands align and twist to form the double helix.
The nonnatural nucleobases form base-pair partners just like DNA’s A-T and G-C. Benner and his team have demonstrated a breakthrough; namely, that when nucleotides containing these nonnatural nucleobases are incorporated into DNA, they don’t distort the DNA double helix.
Even more compelling, the team has shown that DNA polymerases (proteins that make DNA by adding nucleotides, one-by-one, to a single strand of DNA) can use a DNA strand containing nonnatural nucleobases as a template to generate a complementary DNA strand. This achievement means that once they have synthetically made DNA containing the nonnatural nucleobases, these molecules––just like the natural form of DNA––can be replicated using DNA polymerases.
Additionally, DNA polymerases are prone to errors when they assemble a DNA strand. These mistakes alter the DNA sequence, and in effect constitute mutations. Because of these types of mutations, the artificial DNA can evolve. Many scientists consider self-replication and evolvability to be two key properties of life. In fact, in the future Benner’s group hopes to subject these systems to natural selection.
This milestone sets the stage for more ambitious experiments that scientists hope will one day will lead to the creation of artificial life-forms with novel, nonnatural biochemistries. When that day comes, many people will declare that if scientists can make life in the lab, then God isn’t necessary to explain the origin of life.
Not so fast. Instead of providing support for the evolutionary paradigm, I think this accomplishment will demonstrate empirically that, if not for the involvement of an intelligent agent, life could not come about. Benner and his colleagues’ work already hints at that conclusion.
Note the intelligence involved in this process. The preparation of artificial DNA molecules required careful laboratory manipulations on the part of highly skilled and extensively trained chemists. More importantly, to create artificial DNAs, Benner and his team had to develop well-thought-out strategies to design these novel biomolecules. They had to expend a significant amount of mental effort to identify artificial nucleobases that would pair with each other in the DNA double helix without distorting it. They also had to work hard to identify nonnatural nucleobases that would be recognized by DNA polymerases. Even though this work has involved some trial and error, the ingenuity of Benner and his team is evident throughout the experimental design. Given how much effort these scientists expended in their quest for artificial life, is it reasonable to think the highly optimized structure of DNA2 in natural life could have originated via undirected evolutionary processes?
DNA may or may not equate with life. Scientists will continue to debate that statement. However, whether natural or artificial, it increasingly seems that the creation of this molecule requires the work of a Designer––in the case of natural DNA, an extraterrestrial one.
DNA Replication
Biochemists refer to DNA replication as a template-directed, semi-conservative process. By template directed, biochemists mean that the nucleotide sequences of the ‘parent’ DNA molecule function as a template, directing the assembly of the DNA strands of the two ‘daughter’ molecules. By semi-conservative, biochemists mean that after replication, each ‘daughter’ DNA molecule contains one newly formed DNA strand and one strand from the ‘parent’ molecule.
Conceptually, template-directed, semi-conservative DNA replication entails the separation of the ‘parent’ DNA double-helix into two single strands. By using the base-pairing rules, each strand serves as a template for the cell’s machinery to use when it forms a new DNA strand with a nucleotide sequence complementary to the parent strand.
Endnotes
For example see Stephanie A. Havemann et al., “Incorporation of Multiple Sequential Pseudothymidines by DNA Polymerases and Their Impact on DNA Duplex Structure,” Nucleosides, Nucleotides, and Nucleic Acids 27 (2008): 261–78.
See my book, The Cell’s Design (Grand Rapids: Baker, 2008), for a discussion on why DNA’s structure is optimal.
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