On the origin of life.

One of the great unsolved mysteries facing modern biology is the origin of life from non-living material, termed abiogenesis (see here and here). While this is not evolution per se, once life has arisen evolution can proceed. A couple of articles appearing in a recent publication of Gene attempt to tackle two important genetic innovations: the origin of RNA and the origin of the genetic code. RNA molecules and the genetic code are necessary parts of the central dogma of molecular biology, and figuring out how they arose will help us get a clearer picture of biological evolution on earth.

On the origin of RNA:
It is thought that life originated in an "RNA world." The RNA molecules may have been stabilized and protected from environmental hazards by affixing themselves to clay substrates. In order to test the plausibility of this hypothesis, Franchi and Gallori compared RNA degradation on a clay substrate versus free RNA. They also performed experiments to determine whether RNA affixed to clay was self-replicable (an important requirement for biological evolution) .

Franchi and Gallori compared the rate of degradation between free RNA chains and clay-bound RNA chains and found that RNA affixed to the clay substrate has a significantly higher half-life when exposed to chemicals capable of breaking up the RNA chain. This suggests that the substrate somehow protects the molecule from environmental hazards, and that a substrate of some sort may have been necessary during the origin of life.

Was this substrate-bound RNA capable of self-replication? The authors show that clay-bound RNA chains are able to attract and bind free nucleotides and form complementary chains. Furthermore, RNA attached to the substrate was reverse transcribed just as efficiently as free floating RNA. (Reverse transcriptase takes an RNA strand and produces a complementary DNA strand.) These two findings show that RNA bound to a clay substrate is self-replicable -- an essential requirement for life to originate and evolve.

On the origin of the genetic code:
It has been hypothesized that life could have originated as many as 10 different times during primitive earth conditions. Determining where life originated could allow researchers to narrow down the list of possible sources of modern life. Di Giulio believes that there should be a signature of the original environment in the genetic code of modern organisms. Previous research lead to the reconstruction of the rRNA of the last universal common ancestor (LUCA) and led to hypotheses regarding where this organism lived based on its nucleotide content.

[A short aside: The genetic code is made up of four different nucleotides: adenine (A), guanine (G), cytosine (C) , and thymine (T). In RNA molecules, thymine is replace by uracil (U). Adenine binds with thymine and guanine binds with cytosine in the DNA double helix, but these bonds are not equal in strength. Guanine and cytosine are held together by three hydrogen bonds, while adenine and thymine are held together by only two. Geneticists use the percent of guanine and cytosine in a DNA sequence (G+C content) to get an idea of how strong a stretch of DNA double helix is held together. High G+C content regions are held together by more hydrogen bonds than low G+C content regions. It is thought that organisms that live in extreme environments have high G+C content to prevent the high temperature from breaking apart the DNA double helix.]

Di Giulio looked at amino acid content in two different Pyrococcus species -- one that lives 0.5 meters below the surface of the ocean and one that thrives around deep sea vents at high pressures (a barophile). He determined which amino acids are preferentially used in each species, and showed that the amino acids in the barophile are encoded by more codons than those in the non-barophile. He postulates that the number of codons that code for an amino acid reflects the frequency or importance of that amino acid in the genome in which the genetic code evolved (the more codons that code for an amino acid, the higher that amino acid's frequency in the progenitor genome). Because environmental pressures influence amino acid content it is believed that convergent evolution should lead to similar amino acid content between extant organisms and the progenitor genome.

He concludes that the genetic code originated in a barophilic organism because the barophilic Pyrococcus species's genome has amino acids that are encoded by more codons than those in the non-barophile. This approach could also be used to compare amino acid content between organisms living in extreme environments to determine what other conditions lead to the origin of life.

A few closing remarks:
In order for biological evolution to proceed, life must be replicable and be acted on by natural selection. How these features arose is one of the great mysteries in biology. RNA (thought to be the first genetic information) seems to persist and be replicated on clay substrates. We still do not know what enzyme acted as the first RNA replicator, and we do not know how primitive genetic information became encapsulated in a membrane.

Once a primitive nucleotide chain could persists and self replicate, it became possible for it to encode information. Modern DNA and RNA encode information regarding amino acid sequences (proteins) and when, where, and how those proteins should be expressed. Natural selection can act on these proteins and lead to evolution of the coding sequence. It appears that this coding sequence first evolved in a high pressure, deep sea environment. It remains to be seen what other environmental forces were necessary for the evolution of the genetic code.