RL, you missed something in between the dots......
With the advent of RNA replication, Darwinian evolution was possible for the first time. Because of the inevitable copying mistakes, a number of variants of the original template molecules were formed. Some of these variants were replicated faster than others or proved more stable, thereby progressively crowding out less advantaged molecules. Eventually, a single molecular species, combining replicatability and stability in optimal fashion under prevailing conditions, became dominant. This, at the molecular level, is exactly the mechanism postulated by Darwin for the evolution of organisms: fortuitous variation, competition, selection and amplification of the fittest entity.
The scenario is not just a theoretical construct. It has been reenacted many times in the laboratory with the help of a viral replicating enzyme, first in 1967 by the late American biochemist Sol Spiegelman of Columbia University
That was from 1995....don't worry...the science folk are still working on it.
Here's the new stuff:
http://www.hhmi.org/research/investigators/szostak.html
The Origins of Function in Biological Nucleic Acids, Proteins, and Membranes
Summary: To increase understanding of the origin and early evolution of life, Jack Szostak explores the origins of functional biological macromolecules and membranes.
We apply Darwinian principles to evolve new functional molecules in the laboratory. We begin by generating large numbers of nucleic acid or peptide molecules with different sequences. We then impose selective pressure on this population to enrich for sequences with desired properties. Starting with a completely random pool provides a sparse but unbiased sample of sequence space, so that different, independent solutions to a given problem can be obtained. We can sample more than 1015 nucleic acid sequences and, after a few cycles of selection and amplification, recover the descendants of the rare functional molecules in the initial population. In vitro selection for sequences that fold into highly specific binding sites has been used to isolate many nucleic acids, called aptamers, that bind a wide range of small biomolecules, including nucleotides, amino acids, antibiotics, and cofactors.
One fundamental question that we are attempting to address through RNA aptamer selections is the relationship between information content and biochemical function. It seems intuitively obvious that more information should be required to specify or encode a structure that does a better job at performing some function, such as binding a target molecule. We have recently provided the first quantitative demonstration of such a relationship. We approached the problem by isolating a set of distinct aptamers, all of which bind the same target (GTP), but with a wide range of affinities. Our results show that the high-affinity aptamers are much more structurally complex than the low-affinity aptamers. By measuring the amount of information that is required to specify each structure, we were able to show that, on average, it takes about 10 bits of additional information to encode structures that are 10-fold better at binding GTP. Our current work is aimed at understanding the underlying physical basis for the observed relationship between information and function.
We are interested in applying directed evolution to nonstandard nucleic acids, as a way of asking whether life could have evolved using genetic polymers other than RNA. TNA (threose nucleic acid) is a particularly interesting nucleic acid synthesized by Albert Eschenmoser's group (Scripps Research Institute) in a search for possible progenitors of RNA. The sugar-phosphate backbone of TNA uses the four-carbon sugar threose, which might have been easier to come by prebiotically than the ribose of RNA. Despite the one-atom-shorter sugar-phosphate backbone repeat unit, TNA oligonucleotides can base-pair with themselves and with RNA and DNA. We have recently devised an approach to the enzymatic synthesis of TNA libraries, and experiments aimed at the in vitro evolution of TNA aptamers and catalysts are in progress.
The principles of in vitro selection and directed evolution can also be applied to proteins and peptides. We have used mRNA display, which involves the covalent attachment of a newly translated protein to its own mRNA, to select for new functional proteins from a large library of random-sequence polypeptides. Experiments of this sort should allow us to determine whether biology makes use of most of the possible protein folds, or uses only a small subset?-perhaps determined either by functional requirements or historical accident. We are also adapting mRNA display to allow for the synthesis of libraries of small, cyclic, highly modified peptides, similar to those made by the nonribosomal peptide synthases. This may provide a new approach to the isolation of relatively small molecules with a variety of useful functions.
We have recently begun to study the properties of membrane vesicles built from simple amphiphilic molecules such as fatty acids. Such vesicles are models for the compartment boundaries of primitive cells. Since the first cells had no biochemical machinery to mediate the growth and division of their membrane boundaries, there must be purely physical and chemical processes that allow membrane vesicles to grow and divide. Our goal is to find out what those processes could be. Growth turns out to be relatively simple, and Pier Luigi Luisi's lab (then at the Swiss Federal Institute of Technology, Zurich) has shown that fatty acid vesicles can grow by incorporating additional fatty acid supplied in the form of micelles. By combining that process with a procedure for division that forces large vesicles through small pores, we have demonstrated multiple generations of vesicle growth and division. We are currently exploring alternative division processes that might be more prebiotically realistic.
Fatty acid micelles can spontaneously aggregate and self-assemble into membrane vesicles, but this is a slow process with a long lag time. We found that many mineral surfaces abolish this lag phase, somehow helping the micelles to self-organize into membranes. One such mineral is the clay known as montmorillonite?-famous among prebiotic chemists for its activity in assembling activated nucleotides into RNA. Clay particles carrying adsorbed RNA can still help to assemble vesicles and, in the process, bring bound RNA into the interior of the vesicles. The remarkable fact that a simple, abundant mineral can bring together the key components of early life may help to simplify models for the origin of the earliest living cells.
We have recently begun to study the interaction of encapsulated RNA with vesicle membranes composed of single-chain amphiphiles. Encapsulated RNA contributes, through its associated cations, to the internal vesicle osmotic pressure. As a result, vesicles containing RNA are swollen, and the vesicle membrane is under tension; this provides a thermodynamic driving force for the incorporation of additional amphiphilic molecules into the membrane. A consequence is that RNA-containing vesicles grow when mixed with empty vesicles, which shrink as the membrane-forming molecules spontaneously redistribute themselves. This provides a new pathway for vesicle growth, and a potential mechanism by which mutations that enhance the replication of internal RNA could directly affect membrane growth. If faster RNA replication leads to faster membrane growth, and division occurs either stochastically or at a threshold size, the cell cycle will be shorter, leading to faster replication of the entire RNA/vesicle system. We think that this process could have led to the very early emergence of Darwinian evolution at the cellular level.
This work was supported in part by grants from the National Institutes of Health, the National Science Foundation, and NASA.
Last updated: June 27, 2006
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In fact the author candidly admits that he has no clue how, because any chemical pathways to his Nirvana are completely unknown.)