A Word on Evolution

When we think of evolution the first things that come to mind are probably Darwin’s finches, the survival of the fittest and the emergence of ever larger and more complex species that originally derived from single cells. Maybe some people think of how the extinction of dinosaurs allowed mammals to flourish or how the appearance of oxygen-producing cyanobacteria 2.3 billion years ago decimated the number of living species drastically. (According to Wikipedia this event is also known as the Great Oxygenation Event or the Oxygen Holocaust.)

Although I had the opportunity to take a course on “Evolution and Behaviour” during my undergraduate degree, I chose other options instead, including physiology, pathology and (bio)chemistry. Therefore it’s interesting to me how evolution happened on a smaller scale, namely at the level of the molecules that make our cells do what they normally do: DNA – RNA – proteins.

However, cells have not always existed and neither have these molecules. A prominent theory suggests that of those three, RNA evolved first and acted both as an entity that can store information (much like DNA does today) and as a catalyst to drive reactions. This is known as the “RNA world hypothesis” (for a recent review, see Higgs & Lehman, 2015). Although modern cells mainly use proteins to carry out chemical reactions, RNA is still necessary for some very important reactions, including RNA splicing (a necessary part of gene expression in eukaryotes) and protein formation.

The fact that RNA is necessary for the production of proteins from single amino acids strongly supports the idea that RNA preceded proteins during molecular evolution. Today the formation of proteins – also known as protein translation – is carried out by a huge complex, called the ribosome, made of both proteins and RNA:

yeast ribosome

Crystal structure of the S. cerevisiae (yeast) ribosome comprising both RNA and protein – copied directly from Ben-Shem et al., 2010

The ribosome is so large that it proved difficult to study, but when crystal structures finally became available this work was rewarded with the Nobel prize for Chemistry in 2009 (Venkatraman Ramakrishnan, Ada Yonath and Thomas A. Steitz).

Since evolution generally tends from the more simple to the more complex these ribosomes had to gradually come into existence. However, this begs the question how DNA/RNA was translated into proteins before ribosomes? We know now that ribosomes “translate” the so-called genetic code: triplets of RNA bases (adenine A, guanine G, cytosine C and uracil U) get translated into one of twenty amino acids. This code was cracked in the 1960s after the structure of DNA had been solved. There are 64 possible triplets (4x4x4) and only 20 amino acids so that in some cases several triplets encode the same amino acid:

genetic_code_med

Table of the genetic code – copied directly from here.

If one looks at this table a bit more closely it becomes obvious that the code is not random. For example, the amino acid glycine (bottom right) is encoded by four triplets that each start with two guanines, and valine (bottom left) always has G-U at the beginning of its triplets. In theory there are 1.5 x 10^84 possible ways of arranging this table – for comparison, there are approximately 4 x 10^80 atoms in the observable universe – and therefore it is extremely unlikely that the code used today arose by chance.

So how did the genetic code evolve? As in most of science there are several competing, but not necessarily mutually exclusive hypotheses about this. One of them argues that the code arose by natural selection so that mutations at the third base of a triplet would not change the protein sequence. For example, if the DNA sequence GGT were mutated into GGA this would not change the glycine at that position. The code provides robustness to an organism whose DNA is constantly being damaged/mutated. Some scientists therefore propose that the triplet code was originally a quadruplet code – increasing the so-called redundancy – which would have allowed for even more DNA damage without changing the amino acid sequence within a protein.

There are other theories too. Can you think of any? Stay tuned for some exciting news because, yes, there is a good reason that I am writing about this topic and not the more usual CRISPR/cancer.

References:

Ben-Shem A, Jenner L, Yusupova G, Yusupov M (2010) Crystal Structure of the Eukaryotic Ribosome. Science 330: 1203-1209

Higgs PG, Lehman N (2015) The RNA World: molecular cooperation at the origins of life. Nat Rev Genet 16: 7-17

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