Charting progress in our understanding of life

PERHAPS THE greatest remaining mystery in science is the mechanism whereby life spontaneously arose on earth about 3.7 billion years ago.

A breakthrough in the 1950s seemed to promise that rapid progress in this field would follow, but this did not happen. However, recent work, described by Alonso Ricardo and Jack Szostak in the September issue of Scientific American, again offers the promise of further advances in the field.

Life is based on cells that grow, divide, pass on hereditary material, and evolve. The information content of life resides in DNA, the hereditary material. This information is translated into complex agents called proteins, many of whom are catalysts (enzymes) that, with the aid of energy derived from food, perform the work of the cell. When the cell grows and divides into two daughter cells, its DNA content duplicates itself and exact copies of the DNA are passed to each daughter. Enzymes are essential for DNA duplication.

The modern cell offers clues as to how life might have arisen. DNA information is not directly translated into proteins. It is first copied into another information molecule called messenger RNA (mRNA) and the mRNA information is then translated into protein. During the translation process, the mRNA sits on a jig called a ribosome. Part of the structure of the ribosome is another type of RNA – ribosomal (r) RNA. This catalyses the translation of information from mRNA to protein.

Proteins are made from 20 different kinds of units called amino acids and a typical protein has about 100 amino acids strung together end to end. Different types of proteins have different sequences of amino acid.

RNA and DNA represent a class of biochemicals called nucleic acids. Both are similar in structure, but molecular DNA contains two strands whereas RNA is usually single-stranded. RNA and DNA strands are long strings of units called nucleotides. The information content of DNA and RNA resides in the sequence of bases along the length of the nucleotide strings.

The two DNA strands are held together by precise bonds between bases. Base A always bonds to T and G always bonds to C. DNA duplicates itself when its two strands separate and each strand acts as a template on which a second complementary strand forms as new incoming nucleotides settle onto the template through base pairing as already described.

Protein enzymes are essential for DNA duplication, but proteins are too complex to have existed at the dawn of life.

A popular hypothesis is that life first arose on Earth reliant on RNA as the information source rather than on DNA. RNA can also replicate itself in principle by a mechanism like that described for DNA, but how could RNA duplication occur in the absence of protein enzymes? Well, RNA can also act itself as an enzyme and could catalyse its own duplication.

Recent research has demonstrated how the nucleotide sub-units of RNA could spontaneously form from simple chemicals present on the early Earth – cyanide, acetylene, water, formaldehyde, phosphate, and so on – and how these nucleotides could have joined together to form RNA.

This RNA would then have to become segregated into a primitive cell for life to begin.

The modern cell is enclosed in a cell membrane made of phospholipids. Phospholipids spontaneously assemble into membranes. However, simpler lipids called fatty acids also spontaneously form membranes and such a mechanism could have segregated primitive RNA into the first cell. Such primitive cells have been shown to be capable of cell division (like a soap bubble can divide in two) and of allowing the precursor sub-units of RNA to enter from outside, thereby allowing RNA to grow and duplicate itself.

In this way, the first self-replicating cells could have arisen, with their daughters inheriting copies of the parent RNA.

All of the basic components would now be in place to allow Darwinian evolution to occur. DNA, a more stable information molecule than RNA, would later supplant RNA as the primary bearer of genetic information.

This work is at a very early stage and large gaps remain to be filled in. The next major landmark will be to build a simple model of the “first cell”, based on these principles, and see if it can grow and evolve. Such work should add greatly to our understanding of life.

William Reville is associate professor of biochemistry and public awareness of science officer at UCC – http://understandingscience.ucc.ie