11 July 2016 – A number of years ago I became a member of the Natural History Museum in London and that has provided me invitations to some wondrous events. No, I did not get an invite to last week’s Museum of the Year Award dinner at the Museum hosted by Princess Kate. She’s a patron of the Museum as was her mother-in-law Princess Diana. (“Memo to self: up your contribution this year”).
But earlier this year I attended a program on what we have learned from life on Earth, what can we say about alien life. Yes. A bit bizarre but quite fun. Steven Benner has quite a bit to say about this and his presentations are always fascinating.
Note: Benner and his colleagues were the first to synthesize a gene, beginning the field of synthetic biology. He was instrumental in establishing the field of paleogenetics. He is interested in the origin of life and and the chemical conditions and processes needed to produce RNA. Benner has worked with NASA to develop detectors for alien genetic materials.
We take for granted much of what we see in the world around us. We don’t often think about the fact that we have 10 digits on our hands, for example, unless jolted by observing a different life form – The Simpsons perhaps, with their eight digits. For us, our finger number reflects choices made millions of years ago. This number could have been determined simply by accident. Once determined, it may have been difficult to change, therefore persisting in all primates.
Darwinism allows a second explanation: fitness. Primates with 10 digits may have been more likely to survive and have children than primates with eight. Vestigiality is a third explanation. Here, a physiological feature – the human appendix is one example – may have contributed to fitness in the past, but not any longer.
Similar kinds of explanations can be applied to our molecular structures – those that we use to metabolize food, synthesize proteins and procreate, for example. On Earth, all life (that we know of) manages genetic information in the same way by following something called the central dogma. Here, DNA “does” genetics: DNA is copied when we conceive children and translated to make proteins.
DNA, however, is not a good catalyst so is not used directly to catalyze chemical reactions important in metabolism. Rather, information in DNA is transcribed into molecules of RNA which act as messengers. The information in messenger RNA is then translated into proteins using a molecular machine called the ribosome, which is a mixture of RNA and protein. Proteins perform catalytic functions quite well, and so catalyze most of our metabolic functions.
But not all. The RNA parts of ribosomes, not the protein part, make proteins. And RNA is found throughout life on Earth to help proteins catalyse metabolic reactions – for example, a piece of RNA must be attached to the vitamins niacin and riboflavin before they can function in metabolism.
These facts have been used to infer a model for the natural history of our molecular physiology. According to this model, life originally had neither proteins nor DNA, just RNA. In this RNA world, RNA performed both genetic and catalytic functions – somewhat poorly, perhaps, since RNA easily falls apart in water (bad for a genetic molecule) and has too few building blocks to be an effective catalyst.
Therefore, so the story goes, the RNA world invented DNA as a more stable genetic molecule. Then the RNA world invented proteins, which are built from a greater number of building blocks, to be better catalysts. RNA remained behind in life as a vestige of this earlier system, serving as a messenger between the two, in ribosomes and as parts of metabolism.
This way of managing information is everywhere in the biosphere so we rarely question it. But if we do ask “Why?” we realize that bioinformation management could have evolved differently. RNA is a bad catalyst compared with proteins because it is built from only four nucleotide building blocks. However, work in my laboratory over the last quarter century has shown that RNA need not be limited to these four. The bonds which pair the nucleotides in DNA and RNA follow some specific rules: size complementarity (big nucleotides pair with small ones) and hydrogen bonding complementarity (nucleotides that are hydrogen bond donors pair with hydrogen bond acceptors). We observed that natural RNA has not used all possible combinations of big and small, donor and acceptor.
If RNA had been constructed from the 12 different possible nucleotide building blocks it could be a better catalyst, more like proteins. Had Earthly life decided to expand the number of building blocks in RNA rather than inventing proteins, we could be living with a different information and metabolism management system today, one with just two biopolymers, not three. DNA would still be necessary because it is more stable and therefore makes a better permanent genetic molecule. But RNA in its expanded form could directly support metabolism.
Unfortunately, we do not have access to a Simpsonian world where genetic molecules are built from 6, 8, 10 or 12 building blocks. We can, however, synthesise this world ourselves. We can go into the laboratory and make DNA and RNA from expanded genetic alphabets. We can then subject this system to laboratory Darwinism to show that it evolves. We recently did exactly this in collaboration with Weihong Tan at the University of Florida. Our expanded genetic system evolved in the laboratory to give molecules that bind specifically to breast and liver cancer cells.
This is one of the values of the emerging field of synthetic biology. We need not wait until we trip across a Simpsonian life form that manages genetic information differently. We can make one ourselves.
But we may not need to wait much longer for an alien example of a different informational biology. NASA has a rover on the surface of Mars searching for evidence of habitability. And last year NASA reported further evidence for flowing water on the surface of Mars. Both increase the chances that we will find alien Martian life.
But what molecular biology will those still hypothetical Martians have? We do not know, but if we must guess, those guesses must begin with estimating three probabilities:
(a) the probability of life originating as an RNA world,
(b) the probability that an RNA world might generate a ribosome to catalyse protein synthesis, and
(c) the probability that an RNA world might generate an expanded genetic alphabet to allow metabolism to be done by expanded RNA, not proteins. If (c) is more probable than (b), then most alien life will not have proteins. The protein-based life on Earth will be an exception. This is not an unreasonable estimate of the relative probabilities. After all, inventing ribosomes to make proteins by translation of messenger RNA is no small feat, especially if RNA with added building blocks is a better catalyst.
What would protein-free life look like? No one knows, but we can make some educated guesses. Life in the RNA world could easily have cells; back in 1989 Brenner and his colleagues and I found evidence that the RNA world made lipids, which are key parts of cell membranes.
If Martian life and Earth life do not share a common ancestor since the time that the ribosome was invented, we may discover that Martian life has a molecular physiology different from the physiology we take for granted on Earth. Perhaps even eight-fingered yellow life.