September 2010


Was Ice the Original "Cell" in Early Earth?

This post was chosen as an Editor's Selection for How did life arise on Earth? A number of hypotheses are out there, including lightning or a comet impact which may have instigated unusual chemistry leading to amino acid synthesis.

Even if protein-like molecules were the origin of RNA (thought to be the original genetic information carrier), an important question remains. What chemical and physical conditions enabled RNA self-replication in early Earth, a prerequisite for life as we know it?

A number of intriguing hypotheses have been proposed to answer this question, all of them attempting to answer how RNA self-replication became confined to relatively small volumes (e.g. as in modern-day cells). However, the issue is still up in the air, with much room for further debate and discussion.

Philipp Holliger (Medical Research Council, United Kingdom) and coworkers have proposed a new RNA self-replication hypothesis relevant to conditions in early Earth. Their research suggests that ice can enhance RNA self-replication at low temperatures and enable primitive small-scale compartmentation.

RNA enzymatic activity in ice.

The scientists' experiments clearly show that ice has the potential to instigate (bio)chemical reactions. Freezing ice crystals grow and exclude the surrounding solution.

This increases solute concentration (e.g. salt and carbon-based molecules) within the solution, accelerating chemical reactions, including RNA assembly (reminiscent of how intracellular protein crowding dramatically influences biomolecular reactions). The scientists focused their efforts on the R18 polymerase ribozyme, an RNA molecule capable of catalyzing its own synthesis (self-replication).

Importantly, the scientists found that this RNA molecule retains enzymatic activity at -7°C. Although reducing the temperature to -25°C eliminated enzymatic activity, R18 polymerase ribozyme clearly works at low temperatures present in ice.

Further, although enzymatic activity was low at such temperatures, the reactions proceeded for weeks. Thus, even though it took 8 days for R18 polymerase ribozyme to perform the same chemical reactions seen after 2 days at 17°C, enzymatic activity is still clearly present.

Ice protects against changes in salt concentration.

Ice crystallization has additional effects on enzymatic activity retention at reduced temperature, based on the solution concentration effect mentioned previously. This enables R18 polymerase ribozyme to retain enzymatic activity even when the initial magnesium ion concentration is dramatically reduced (depending on the counterion, e.g. chloride or sulfate).

Only so many ions can be excluded from the ice; only below this maximum concentration (i.e. roughly below magnesium ion concentrations in freshwater today) is the effect of initial solution concentration observed. In other words, more dilute initial concentrations (down to a critical value) do not reduce final solution concentrations.

In contrast, enzymatic activity is greatly reduced under the low-magnesium conditions found in dilute solutions at 17°C. Additionally, the duration of R18 polymerase ribozyme activity at the high magnesium concentrations required for high activity is enhanced at -7°C by over a factor of 7, relative to activity at 17°C, and self-replication proceeds with high fidelity at both temperatures (over 95%).

Ice has a clear protective effect on RNA biomolecular function at reduced temperatures. The protective effect extends to biomolecular isolation from the surrounding medium, as discussed next.

RNA compartmentation in ice.

A major limitation of some hypotheses regarding RNA self-replication in early Earth is that they do not clearly offer a means of permanently isolating (compartmenting) RNA from the surrounding environment, as is done for biomolecules in living cells today. RNA which is "free to swim around the world" might have many interesting adventures and photo-ops, but is more susceptible to degradation, and is much less likely to become organized into multicomponent assemblies (i.e. as in living cells today).

Ice may provide an answer to this challenge. Ice possesses a microscopic structure of channels and voids between the crystals; can these structures enable primitive RNA compartmentation?

The scientists fabricated an artificial ice column, decorated with microparticles which promote R18 polymerase ribozyme activity. They found that the RNA enzymes required a week to reach 70% of the microparticles; dramatically reduced biomolecular diffusion can be reasonably considered as primitive compartmentation.

The physical basis of reduced biomolecular diffusion is likely the fragmented nature of the ice network, with less connectivity between channels as the ice crystals grow in size. This effect is dramatically influenced by both magnesium ion concentration and magnesium counterion identity.

Surface effects cannot be ruled out on this data alone. However, computer simulations suggest the scientists' ice network connectivity hypothesis.

Overall evaluation.

Holliger and coworkers clearly aren't saying that life as we commonly know it today can exist just as well in ice as at warmer temperatures. They're instead saying that ice provides a plausible means of enhancing RNA self-replication activity and protecting it from the surrounding environment, in conditions likely found in early Earth.

This research doesn't exclude other hypotheses of "the origin of life;" rather, it's an additional hypothesis that overcomes many limitations of those previously proposed. Ice deserves serious consideration as the first living "cell" in early Earth.

NOTE: The scientists report no sources of funding for their research.
Attwater, J., Wochner, A., Pinheiro, V. B., Coulson, A., & Holliger, P. (2010). Ice as a protocellular medium for RNA replication Nature Communications, 1 (6), 1-8 DOI: 10.1038/ncomms1076