The deepest origins of genetic information
The observation that RNA sequences can bind amino acids hints at something very important: proteins are not the only type of molecule that can spontaneously fold into shapes with interesting properties. As described in the companion paper by Watts, sequences of RNA can exhibit protein-like behavior. Technologies first developed in the 1980’s and 1990’s have been used to lab-evolve a wide variety of molecules, dubbed ribozymes in deference to the previously known class of protein catalysts known as enzymes. These ribozymes now cover most steps of fundamental biochemistry (such linking together carbon atoms to make important biological molecules.) Proteins are much less necessary for life than they seemed a couple of decades ago. This observation finds unlooked-for synergy with another line of scientific discoveries. In modern living systems, not all RNA performs the simple role of carrying genetic information from DNA to be decoded into proteins. A handful of the genes that are faithfully copied from DNA into RNA fold up into a complex three-dimensional shapes that act as if they were proteins. Interestingly, these natural ribozymes tend to occur in the most ancient metabolic pathways – those shared by bacteria, humans and everything else alive today. Aspects of biology that have not changed much in billions of years of evolution are likely still with us because they have been doing their job very well throughout this period. In other words, this type of RNA behaving like a protein is exactly what one might expect to see if the ribozymes produced by SELEX resemble a stage of our truly ancient evolutionary past when genetic coding of proteins was far less important (if it was present at all.) Oddly enough, Crick (of the Frozen Accident) had suggested something similar to this concept of molecular fossils when he looked at how genetic de-coding works. He noticed that the adaptor molecules responsible for decoding individual genetic code-words into specific amino acids are nothing more than folded-up RNA. He also noticed that the biggest and most complex molecular machine involved with genetic de-coding (the ribosome) seemed to be made of RNA with a few proteins thrown in for good measure. Three decades later, new technology allowed researchers enough precision in their study of the ribosome’s structure to confirm this is correct: although proteins are embedded within the tangled, folded RNA, they appear to offer little more than structural enhancements.1 At its core, the ribosome is a ribozyme. It seems likely that a primitive ribosome could function without any encoded proteins: exactly what we would expect if genetically encoded proteins emerged from a simpler, earlier world in which only RNA existed.
Of equal interest, everything points towards DNA being the last arrival out of the 3 fundamental biomolecules: DNA, RNA and protein.2 DNA is made by complex, genetically encoded protein enzymes without a ribozyme in sight. The individual building-blocks of DNA (deoxynucleotides) are made by taking and modifying a nucleotide of RNA. Again, all this is exactly what we would expect if DNA evolved from RNA, after genetically encoded proteins had already entered the picture. Indeed, DNA is a more chemically inert version of RNA – better for safe storage of genetic information, worse for folding up into a catalyst. This is what you might expect if it emerged after RNA had already handed off the job of catalysis to genetically encoded protein enzymes. The RNA would get left sandwiched in the middle of DNA and proteins, just where we find it today (Box 1).
Observations that expand on all of these themes continue to accumulate and are beginning to sketch a framework that was completely unknown in the mid 1960’s. At its best, this “RNA-world” hypothesis solves much of the puzzle for the origin of living systems. One molecule, RNA, is its own catalyst and information carrier. However, many puzzles remain. For instance, the universe seems quite good at making amino acids without life. They have been found in meteorites, formed in simulations of the conditions of interstellar space and turn up reliably in just about every possible simulation of our planet’s early conditions. For nucleotides, the building-blocks of RNA, the exact reverse is true. It seems relatively simple to make the nucleobases (such as Adenine and Guanine)– but these must be chemically linked to a ribose sugar and a phosphate in order to make a single nucleotide in processes that are antagonistic to those in which the bases form: there are real chemical difficulties in forming the individual nucleotide building blocks, and even bigger difficulties for linking them together into sequences that do not also contain all sorts of unwanted molecular garbage.3 If RNA came first then why is it so much easier to make amino acids than RNA from non-biological scratch?
Scientists are relatively confident that an RNA-protein world preceded ours in which DNA genes are copied into mRNA transcripts en route to protein translation. Every clue that we can find supports this conclusion. What is much less certain is how the RNA-protein world itself emerged. One broad class of ideas asserts that we have simply failed to discover some set of conditions that encourages sequences of RNA to form spontaneously. Mineral surfaces are often mentioned here, as they can catalyze many chemical reactions. For example in 2004, the mineral borate was shown to catalyze the notoriously difficult synthesis of ribose - an essential component of the chemical structure of every single nucleotide.4 Perhaps other minerals will be found to help other steps in nucleotide synthesis, and for linking nucleotides into sequences. Certainly chemists, geologists and biologists are talking more than ever before as they seek to add up their knowledge of the ways in which life, chemistry and the planet interact. Among them, increasing attention is coming to focus on hydrothermal vents as a good place to look next in the search for the origin of life.5 Here, hot water full of interesting chemicals is forced to flow over richly diverse mineral. This can produce a slew of chemical reactions, most of which are still poorly understood.
Another view is that searching for non-biological origins for RNA is looking in the wrong place. Instead, genetic information, at least in the form that we think of it (polymerized nucleotide sequences) was itself an evolutionary invention of an earlier metabolism, a pre-RNA world. Perhaps significantly, proponents here are also drawn to minerals and to hydrothermal vents because the same conditions that might aid nucleotide synthesis produce a slew of interesting and newly discovered chemical reactions.6
It might even be that these two views meet up one day. Since the mid-1960s, a scientist by the name of Grayham Cairns Smith has been proposing that minerals were the original genetic information.7 Crystalline minerals show the interesting property of harnessing energy from the environment to grow by making copies of themselves. As they do this, they are creating chemical order from chaos. That is exactly what a salt crystal is doing as you watch saltwater evaporate in a glass or a rock-pool. They might also catalyze specific chemical reactions on their surface according to their exact atomic composition.8 In effect, they might carry simple genetic information that starts to trap the energy flowing through the system into a chemical reflection of the environment. But by now we are talking about one of the swarm of competing ideas at the edge of Category 2. Here they will compete and rise or fall according to the evidence that can be gathered through careful and ingenious tests.
Evolutionary theory, like any other branch of science, achieves progress by testing new ideas. Some of these ideas will go on to change what we thought we knew, others will be found incorrect, and some will stagnate as they fail to gather clear evidence, for or against. For evolutionary theory, many suggestions have been made for new causal factors that are required to explain how genetic diversity has arisen. Intelligent Design, for example, proposes that some types of genetic information cannot evolve through natural processes unless we admit a role for an intelligent designer. This proposition claims testability by using a definition of information that usually refers to creation by an intelligent agent. Meanwhile, many biologists perceive that they are able to understand exactly where life’s genetic information comes from (the local environment) by thinking in terms of more fundamental and well-established definitions of information that do not involve Intelligent Design. A related suggestion is that current evolutionary theory cannot explain how natural processes could produce a genetic information system in the first place. I agree that we are far from a full understanding, but choose to outline some major themes in the scientific progress made since the discovery of life’s Central Dogma in 1966 to provide a context for the reader to judge for themselves whether it is time to conclude that this search has failed.
It would be remiss to finish an article in this journal without some comment on the theology of all this. If we accept the evolutionary explanations sketched above, then science is taking major steps towards understanding the mechanism by which life came into the universe. Some famous advocates of this science claim it presents a logical connection to an atheistic world-view.9 Many others (myself included) perceive that any connection between evolution and spirituality is an act of faith – and faith in atheism is only one of many options.10 For my part, I find excitement and challenge in the search to unravel this marvelous mystery. I choose to associate that inspiration with a loving, creator God whose universe I am exploring. I agree with Dawkins (and Darwin) that from a human standpoint, the suffering and death implicit to natural selection form questions for my faith – and I am grateful that scientists and theologians are able to discuss such issues in forums such as this11, where I can read, learn and grow my relationship with God through an exploration of science.
Q1: “…the universe seems quite good at making amino acids without life. They have been found in meteorites, formed in simulations of the conditions of interstellar space and turn up reliably in just about every possible simulation of our planet’s early conditions.” If the building blocks of life can, and do, exist outside of earth’s life-filled atmosphere, do you think it’s also possible that life, itself, exists elsewhere in the universe? If so, and if that life is intelligent, how might the discovery of reason-endowed extraterrestrials affect your own beliefs about human exceptionalism? What do you think should be our Christian approach to interacting with extra-terrestrials, should we ever come across any?
Q2: “I agree with Dawkins (and Darwin) that from a human standpoint, the suffering and death implicit to natural selection form questions for my faith…” Many of the criticisms atheists make concerning Christian faith hinge on the idea that no loving creator God would allow—especially plan for—his creatures to suffer as much as they do. Does “the suffering and death implicit in natural selection” create complications for your Christian faith? How about your acceptance of evolution, itself?
Q3: Do you accept evolution and the “RNA-world” hypothesis of the origins of life on earth? Why or why not? We see in our own house pets and in the behavior of various animal species a capacity for problem-solving, for play, and for emotional commitments that resemble love. With this in mind, do you think it’s possible for other animals to evolve to the point where they, too, can have a relationship with God?
Q4: Throughout the four parts of this essay, a consistent theme has highlighted the incompleteness of human scientific knowledge, and the limitations of specific human approaches (e.g. systems of measurement) in representing reality (truth). How do you think these themes of imperfect human understanding translate from science into theology, and what does this concept contribute to the ongoing debate between science and religion?
1. For an introduction and references to more detailed material, see Cech TR “The ribosome is a ribozyme” Science (2000) 289:878-9
2. A brief review of data here is found in S.J. Freeland, R.D. Knight, L.F. Landweber “Do Proteins Predate DNA?” Science (1999) 286: 690-692.
3. Readers who are interested in this particular sub-topic are encouraged to read Robert Shapiro’s article “A Simpler Origin for Life”, Scientific American, June 2007 pp. 47-53. Shapiro’s passionate emphasis represents the best traditions of scientific skepticism, ruthlessly pointing out some very real problems with all current attempts to how a non-living universe could have produced RNA. In particular, widespread enthusiasm for the RNA-world has become so fashionable that even high-profile scientific publications which explicitly seek to demonstrate pre-biotic origins for the RNA world continue to ignore well-understood and long-standing criticism of the problems. For example, one recent, high-profile paper claims to demonstrate prebiotic plausibility for synthesis of nucleotides (Powner MW, Gerland B, Sutherland JD. “Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions.” Nature (2009) 459:239-42.) This interesting work shows that exactly the right purified solution of linear organic molecules can cyclize under the right conditions to present activated nucleotides. However, it entirely misses Shapiro’s “garbage bag” point - that one of the biggest challenges for understanding the evolution of an RNA-world is to understand how building blocks form into oligonucleotides when they are coming from any sort of messy molecular organic broth (rather than a purified solution of exactly the right reactants under exactly the right conditions.) There is no chemical reason why nucleotides should form and stick to one another rather than to other chemicals produced in the same broth – such as amino acids, alcohols, esters etc. Of further note, the chemistry reported in this Nature paper bears no resemblance to the reactions by which living organisms have been making nucleotides for more than 3 billion years. Maybe early life changed its metabolic pathways beyond recognition - but as yet we have absolutely no evidence for this whatsoever: Prebiotically possible and prebiotically plausible are subtly different concepts.
4. For example, see the comment by Steve Benner on page 52 of ref. 32. For a more detailed treatment, see Kim HJ, Ricardo A, Illangkoon HI, Kim MJ, Carrigan MA, Frye F, Benner SA., “Synthesis of carbohydrates in mineral-guided prebiotic cycles.”, Journal of the American Chemical Society (2011) 133:9457-68.
5. A very readable overview of this topic can be found in the first chapter of Nick Lane’s recent book “Life Ascending: The Ten Great Inventions of Evolution” (2009, W.W. Norton, New York)
6. One recent example is given by Mielke RE, Russell MJ, Wilson PR, McGlynn SE, Coleman M, Kidd R, Kanik I “Design, fabrication, and test of a hydrothermal reactor for origin-of-life experiments.” Astrobiology (2010) 10:799-810.
7. Although Cairns Smith’s ideas date back to the mid 1960’s, they are most accessibly presented in his later book: “Seven Clues to the Origin of Life.” (1985, Cambridge University Press, New York)
8. For a broad introduction to this progress, as of 2001, see “Life’s Rocky Start” by Robert M. Hazen, Scientific American (2001) 284: pp. 77-85
9. For example, see Chapter 4 (“God’s utility function” Pages 95-135) of Richard Dawkins book River out of Eden (Basic Books/Perseus, New York, 1995)
10. For example, see the letter(s) and signatories of the Clergy Letter Project: http://www.theclergyletterproject.org/
11. For example, the excellent pair of articles: Junghyungkim “Naturalistic versus Eschatological Theologies of Evolution” Perspectives and Keith Miller “And God saw that it was good” – both within Perspectives in Science and Christian Faith (2011) 63(2).