One
of the greatest mysteries, which continuously fascinate many scientists
worldwide, concerns the way by which life emerged on primeval Earth. The
accepted notion is that prior to the appearance of living organisms, there was
a stage of chemical evolution, which involved selection within inanimate
chemical mixtures. This is thought to have eventually led to the crucial
moment, when self-replicating molecules arose. As self-replication is a most
fundamental characteristic of living entities, such an event is often defined
as the birth of life.
Self-replication of molecular systems is often viewed in the context of
information content. Many scientists believe that life began with the
spontaneous emergence of biopolymers, such as proteins or RNA, where
information is stored in the sequence of chemical units. Experiments mimicking
the conditions on Earth billions of years ago have shown how such chemical
units, e.g. some of the building blocks of proteins and RNA, could appear
spontaneously. Yet, the emergence of proteins or self-replicating RNA molecules
remained enigmatic.
This started Prof. Doron Lancet of the Molecular Genetics Department in the
Weizmann Institute of Science, and his students, Daniel Segre and Dafna
Ben-Eli, on a journey leading to alternatives to proteins and RNA. They have
developed a model, suggesting a new route for the origin of life, based on
lipid molecules. This model is described in an article published a recent issue
of the Proceedings of the National Academy of Science, USA.
Lipids are oily substances, known as chief ingredients of the cell's membranes.
Lipids have two different aspects one hydrophilic (water-attracting), and the
other hydrophobic (water-repelling). They get readily synthesized under
simulated prebiological conditions, and because of their bipartite nature, have
the tendency to spontaneously form supramolecular structures made of thousands
of molecular units. This is exemplified in lipid assemblies (micelles), which
have even been shown to be capable of growing and splitting in a fashion
reminiscent of cell replication. Yet a critical question was left unanswered:
how could lipid assemblies carry and propagate information.
The model proposed by Lancet and colleagues offers a solution. They surmise
that early on, lipid-like compounds existed in a very large diversity of shapes
and forms. They show mathematically that under such conditions, lipid
assemblies could contain almost as much information as an RNA strand or a
protein chain. Information would be stored in the assembly's composition, i.e.
in the exact amount of each of its compounds, rather than in a sequence of
molecular 'beads' on a string. A useful analogy would be that of perfume: the
information - the scent as discerned by receptors in the nose - depends on each
ingredient's proportion in the mixture, but the order in which aromas are added
is unimportant.
Thus, the authors argue, heterogeneous lipid assemblies may be thought of as
having a 'compositional genome'. They further demonstrate how a droplet-like
lipid assembly, when growing and splitting, could manifest a form of
inheritance. Their computer simulations show how a compositional genome would
be handed down with some fidelity to the offspring assemblies. A crucial aspect
of the model is how such molecular inheritance is made possible. In present-day
cells, the replication of information-containing DNA is facilitated by protein
enzyme catalysts. In the early prebiological era, catalysis could be performed
by the same lipid-like substances that carry the information. Molecules already
present inside a droplet would function as a molecular selection committee,
enhancing the rate of entry for some, and rejecting others.
Lancet, Segre, and Ben-Eli designed a computerized simulation that shows how,
based solely on physiochemical principles, lipid droplets with idiosyncratic
compositions accrete, grow, split, self-replicate, accumulate compositional
mutations, and get involved in a complex evolutionary game. Importantly, it is
entire assemblies, with their complex mixtures of relatively small molecules
that are replicated. This differs from the older models, in which a single,
long RNA polymer is what gets copied. The scientists' model makes very few
chemical assumptions and derives a rich molecular behavior reminiscent of life
processes. It therefore has the potential of constituting the long-sought
bridge leading from the inanimate world to that of living organisms.
This research has already attracted considerable interest, and was quoted in
the recently published new edition of the classic book Origins of Life by
Freeman Dyson from the Princeton Institute of Advanced Study. The next
important question to be answered: how could lipid droplets undergo the
numerous transitions needed to lead to living cells as we now know them? In
this sense, the study marks the first footfall in a long journey to come.