Thursday, September 22, 2005

Interesting News on RNA, DNA and the Evolution of Protein

Regular readers of this blog know that I that I get a lot of science news from Science Daily and frequently turn that news into a post. This post is no exception. I have come across several interesting articles on RNA, DNA, protein evolution and lifes origins (one of which I have blogged about before).

The first concerns the RNA world:

In the primordial soup that produced life on earth, there were organic molecules that combined to produce the first nucleic acid chains, which were the first elements able to self-replicate. According to one of the more accepted theories, these molecules were ribonucleic acid (RNA) chains, a molecule that is practically identical to DNA and that today has the secondary role in cells of copying information stored in DNA and translating it into proteins. These proteins have a direct active role in the chemical reactions of the cell. In the early stages of life, it seems that the first RNA chains would have had the dual role of self-replicating (as is today the case with DNA) and participating actively in the chemical reactions of the cell activity. Because of their dual role, these cells are called ribozymes (a contraction of the words ribosome and enzyme). But there is an important obstacle to the theory of ribozymes as the origin of life: they could not be very large in length as they would not be able to correct the replication errors (mutations). Therefore they were unable to contain enough genes even to develop the most simple organisms.


Recent research has indicated a likely way around the limiting factor of length mainly because the replication error rate is higher than previously thought:

In practice, this means that the first riboorganisms (protocells in which RNA is responsible for genetic information and metabolic reactions) could have a much bigger genome than was previously thought: they could contain more than 100 different genes, each measuring 70 bases in length (bases are the units that constitute the genes and codify the information), or more than 70 genes, each measuring 100 bases. It is worth remembering that tRNAs (essential molecules for the synthesis of proteins) are approximately 70 bases long.


This is important because previous research indicates that the minimum number of DNA genes needed for simple organisms is about 200 but:

But in riboorganisms there can be much fewer genes, since DNA genomes include a number of genes that have the role of making the RNA translation system (which enables proteins to be produced) work, which would not be required in RNA-based organism.


Which brings us to the second article (published in 2002). Two scientists at the Scripps Research Center created an enzyme based on a binary genetic code - that is a genetic code having only two different subunits (which I assume means bases). The research demonstrated that evolution can occur in a genetic system composed of two bases and shows that an early life form could exist with only two bases:

Where protein enzymes are polymer strings made up of 20 building blocks (the amino acids), and RNA or DNA enzymes are made up of four different building blocks (the nucleotides), the world's first binary enzyme has but two different building blocks, based on the nucleotides A and U.

This enzyme is functionally equivalent to a "polymerase" molecule. Polymerases are ubiquitous in nature as the enzymes tasked with taking a "template" string of DNA or RNA bits and making copies of it.

Reader and Joyce's binary enzyme is able to join pieces of RNA that are composed of the same two nucleotide symbols. In the test tube, the binary string folds into an active three-dimensional structure and uses a portion of this string as a template. On the template, it "ligates," or joins subunits together, copying the template.


*snip*

One of the great advances in the last few decades has been the notion that at one time life was ruled by RNA-based life--an "RNA world" in which RNA enzymes were the chief catalytic molecules and RNA nucleotides were the building blocks that stored genetic information.

"It's pretty clear that there was a time when life was based on RNA," says Joyce, "not just because it's feasible that RNA can be a gene and an enzyme and can evolve, but because we really think it happened historically."

However, RNA is probably not the initial molecule of life, because one of the four RNA bases--"C"--is chemically unstable. It readily degrades into U, and may not have been abundant enough on early Earth for a four-base genetic system to have been feasible.


Which brings us to the third article (published in April of 05). Scientists at Scripps Research Center successfully created a third base pair. There are basically only two in DNA guanine-cytosin and adenine-thymine:

Scripps Research scientists’ DNA has a third pairing: “3FB-3FB” between two unnatural bases called 3-fluorobenzene (or 3FB). Unlike other unnatural base pairs, DNA polymerases are able to replicate this base pair, albeit with reduced fidelity. To improve replication, the scientists also reported the development of a system capable of evolving polymerases to better recognize 3FB in DNA. Using a selection system some liken to evolution in the test tube, they are creating their own “polymerase” enzyme able to replicate the unnatural DNA.

While the polymerase does not replicate the unnatural DNA with the same fidelity observed in nature, (roughly one mistake for every 10 million bases of DNA copied), its fidelity is reasonable (typically making only one mistake for every 1000 base pairs). This is the first time anyone has been able to replicate unnatural DNA with fidelity against every possible mispair.


Which demonstrates that it is possible for things to have evolved from a system with just say g-c or a-t to a system with both.

Which brings us to the fourth article (which I have blogged about previously):

As the DNA ‘alphabet’ contains four letters - called bases - there are as many as 64 three-letter words available in the DNA dictionary. This is because it is mathematically possible to produce 64 three-letter words from any combination of four letters.

But why there should be 64 words in the DNA dictionary which translate into just 20 amino acids, and why a process that is more complex than it needs to be should have evolved in the first place, has puzzled scientists for the last 40 years.


*snip*

One of quirks of the genetic code is that there are groups of codons which all translate to the same amino acid. For example, the amino acid leucine can be translated from six different codons whilst some amino acids, which have equally important functions and are translated in the same amount, have just one.

The new theory builds on an original idea suggested by Francis Crick - one of the discoverers of the structure of DNA - that the three-letter code evolved from a simpler two-letter code, although Crick thought the difference in number was simply an accident “frozen in time”.

The University of Bath researchers suggest that the primordial ‘doublet’ code was read in threes - but with only either the first two ‘prefix’ or last two ‘suffix’ pairs of bases being actively read.

By combining arrangements of these doublet codes together, the scientists can replicate the table of amino acids - explaining why some amino acids can be translated from groups of 2, 4 or 6 codons. They can also show how the groups of water loving (hydrophilic) and water-hating (hydrophobic) amino acids emerge naturally in the table, evolving from overlapping ‘prefix’ and ‘suffix’ codons.

“When you evolve our theory for a doublet system into a triplet system, you get an exact match up with the number and range of amino acids we see today,” said Dr van den Elsen, who has worked with Dr Stefan Babgy and Huan-Lin Wu on the theory.


*snip*

The theory also explains how the structure of the genetic code maximises error tolerance. For instance, ‘slippage’ in the translation process tends to produce another amino acid with the same characteristics, and explains why the DNA code is so good at maintaining its integrity.

“This is important because these kinds of mistakes can be fatal for an organism,” said Dr van den Elsen. “None of the older theories can explain how this error tolerant structure might have arisen.”

The new theory also highlights two amino acids that can be excluded from the doublet system and are likely to be relatively recent ‘acquisitions’ by the genetic code. As these amino acids - glutamine and asparagine - are unable to hold their shape in high temperatures, this suggests that heat prevented them from being acquired by the code at some point in the past.

One possible reason for this is that the Last Universal Common Ancestor (LUCA), which evolved into all life on earth, lived in a hot sulphurous pool or thermal vent. As it moved into cooler conditions, it was able to take up these two additional amino acids and evolve into more complex organisms. This provides further evidence for the debate on whether life emerged from a hot or cold primordial soup.


Which brings us to the fifth article which discusses the evolution of proteins:

By examining how proteins have evolved, UT Southwestern Medical Center researchers have discovered a set of simple "rules" that nature appears to use to design proteins, rules the scientists have now employed to create artificial proteins that look and function just like their natural counterparts.


*snip*

"The goal of our research was not to find another way to make artificial proteins in the lab, but to discover the rules that nature and evolution have used to design proteins," Dr. Ranganathan said. "The rules we have extracted from the evolutionary record of proteins contain a substantial fraction of the information required to rebuild modern-day proteins. We're building solutions so close that, at least in a test tube, we can't tell them apart from natural proteins."


Here is how it works:

"How did nature devise the right sequences that resulted in functioning proteins? Somehow, it found a way," Dr. Ranganathan said. "One implication of our work is that the evolutionary protein-design process may not be as complex as was previously thought." (oooh, Behe's going to be bummed - afarensis)

Earlier research has shown that for a given group of related proteins, or protein family, all family members share common structures and functions. By examining more than 100 members of one protein family, the UT Southwestern group found that the proteins share a specific pattern of amino acid selection rules that are unique to that family.

"What we have found is the body of information that is fundamentally ancient within each protein family, and that information is enough to specify the structure of modern-day proteins," Dr. Ranganathan said.

He and his team tested their newly discovered "rules" gleaned from the evolutionary record by feeding them into a computer program they developed. The program generated sequences of amino acids, which the researchers then "back-translated" to create artificial genes. Once inserted into laboratory bacteria, the genes produced artificial proteins as predicted.

"We found that when isolated, our artificial proteins exhibit the same range of structure and function that is exhibited by the starting set of natural proteins," Dr. Ranganathan said. "The real test will be to put them back into a living organism such as yeast or fruit flies and see how they compete with natural proteins in an evolutionary sense."


Put them all together and a theory about the origins of life begins to emerge. The is one caveat though (going back to the second article):

If the origins of life are a philosopher's dream, then they are also a historian's nightmare. There are no known "sources," no fossils, that show us what the very earliest life on earth looked like.


*snip*

Since the fossil record may not show us how life began, what scientists can do is to determine, in a general way, how life-like attributes can emerge within complex chemical systems. The goal is not necessarily to answer how life did emerge in our early, chemical world, but to discover how life does emerge in any chemical world--to ask not just what happens in the past, but what happens in general.


The part in bold is, if you ask me, the most important point of the second article. We may never be able to have an exact blow by blow account of life's origins. What we can do, however, is indicate that under a certain set of given conditions life can arise. More importantly, we should eventually be able to indicate the conditions under which life can be expected to arise. The two are different. In the first case (think the Miller-Urey experiments) the initial conditions are specified and life may or may not develop under those circumstances. The point is that you are applying a theory to a particular case. The second instance is more generalized - or better yet operates at a higher theoretical level. In this case we can specify a range of conditions under which life should develop.

But, those of you who know a lot about science may be thinking "what about Brownian Motion?" "Surely", you say "Einstein proves everything you have just written is wrong" This brings us to our sixth article which is actually about UV damage to DNA rather than Brownian Motion. It is relevant, however:

In the current issue of the journal Nature, Bern Kohler and his colleagues report that DNA dissipates the energy from ultraviolet (UV) radiation in a kind of energy wave that travels up the edge of the DNA molecule, as if the energy were climbing one side of the helical DNA “ladder.”

The finding lends insight into how DNA damage occurs along the ladder's edge.

It also counters what scientists proposed in the 1960s: that UV causes mutations by damaging the bonds between base pairs – the horizontal “rungs” on the ladder. The new study shows that UV energy moves vertically, between successive bases.


*snip*

In undamaged DNA, there are no chemical bonds between vertically stacked bases. But the bases do interact electronically, which is why Kohler thinks they form an efficient conduit for UV energy to flow through.

“Even though paired bases are connected by weak chemical bonds, it's the interactions that take place without chemical bonds – the interactions between stacked bases – that are much more important for dissipating UV energy,” Kohler said.


*snip*

Their new experiments show that the behavior of full DNA differs profoundly from that of isolated bases. When the chemists turned their strobe light on whole strands of novel DNA, the UV energy still changed to heat eventually, but the energy dissipated a thousand times more slowly.

That's an eternity in the DNA universe, where scientists need to use special equipment just to see these ultra-fast chemical reactions happen. Yet, Kohler's team saw no evidence that the UV affected the chemical bonds between the base pairs. They surmised that the UV energy was leaving the molecule by traveling along the edges instead.

“This slow relaxation of energy is utterly different from the mechanism in single bases that transforms the energy into heat in less than a trillionth of a second,” Kohler said.

“Eventually, the energy does turn into heat, but the important point is that the energy is retained within the molecule for much longer times,” he added. “This can cause all kinds of photochemical havoc.”

It could be that when base pairs are aligned in their natural state in a DNA strand, the electronic interactions along the stack provide an easier way for DNA to rid itself of UV energy, compared to passing the energy back and forth between the two bases in a base pair as scientists have previously thought.


Although Brownian Motion and UV radiation are two different things I would expect that the energy gained via the effects of Brownian Motion (I assume Birdnow meant that - well never mind I'm not sure what Birdnow meant)would be dissapated in a similar manner.