The great mysteries of life are biochemical

SOME OF THE greatest mysteries in science are chemical mysteries. Philip Ball lists 10 of these mysteries in the October issue of Scientific Americanand I will discuss two biochemical examples today.

The Origin of Life:Life first appeared on Earth almost four billion years ago and science assumes that this was a spontaneous event. Lifeless organic molecules that had chemically evolved over millions of years in Earth's primordial seas spontaneously self-assembled to form the first living cells – cells capable of processing energy and replicating themselves. Various scenarios have been proposed to describe this process, for example life arising in an "RNA World" – a leading proponent of this scenario is Prof John Atkins, Biochemistry Dept, UCC.

Life on Earth is now based on DNA but the RNA-World scenario envisages life arising in an RNA-based form. RNA resembles DNA in that both molecules are large polymers made of the same building blocks – nucleotides – but it differs from DNA in that some forms of RNA can also act as catalysts (enzymes) that could speed up and direct the chemical reactions necessary to underpin the first living cells. Recent research demonstrated that nucleotides can form from simpler molecules that probably existed in the primordial seas.

Progress towards understanding the spontaneous beginnings of life from inanimate matter (abiogenesis) is slow. Indeed, the spontaneous origin of life may have been a unique event whose details will never be discovered. Fred Hoyle (1915-2001), the British astrophysicist, was a pessimist. He said: “If there were some deep principle that drove organic systems towards living systems, the operation of such a principle should easily be demonstrable in a test tube in half a morning. Needless to say, no such demonstration has ever been given.” Hoyle did not believe in the Big Bang theory. He believed in a steady state universe that always existed. He believed life began and developed elsewhere in the universe over a vast time-span and seeded on Earth about four billion years ago.

How Our Genes are Affected by the Environment:Our basic genetic information resides in our genes but the expression of this information is subject to the subtlest control. For example, every cell in your body contains all your genetic information, but each tissue type has a unique pattern of genetic activity – some genes are switched on and others off.

Genetic information is written in linear code on long molecules of DNA and, in order for the cell to read the information on the gene the DNA must be stretched lengthwise. The genes are arranged and packaged, together with proteins called histones, into structures called chromosomes. Those parts of the chromosome containing genes that must be read (“switched on”) in a particular tissue type are stretched out whereas parts containing genes that are “switched off” are tightly coiled up.

The DNA and the histone proteins have “epigenetic” chemical markers which, depending on the signals they receive from the environment, either cause regions of the chromosome to coil up, making the genes that these regions carry unavailable for use, or to lengthen out making the genes available. The epigenetic markers do not alter the genetic information present on the genes, they cause the genes to switch off or on, for example, chromosomes from a sheep’s udder cell were inserted into an egg cell from another sheep, after that egg had its own chromosomes removed. Different sets of genes are active in udder cells than in egg cells.

But, as we now know, the environment of the egg cell can activate the appropriate “egg genes” in the udder chromosomes, transforming them into chromosomes characteristic of fertilised egg cells, thereby allowing a sheep embryo to form. This is how Dolly was born in 1996.

What we are depends not only on which genes we have but on which genes we use, for example you might have a gene that predisposes you to develop a certain disease but whether or not the disease develops often depends on environmental factors operating through epigenetic signalling.

The human genome project told us how many genes we have. We still do not know what many of these genes do and little of how gene expression is controlled. We remain at the start of a long road in understanding molecular human genetics.

William Reville is a Professor of Biochemistry and Public Awareness of Science Officer at UCC. http://understandingscience.ucc.ie