Chapter 12: Self-Assembly (Genome)

•There are many analogies between human beings and nature, but one of the most difficult to understand is how a fertilized egg develops into a human body.

• Genes contain the plan for development in digital form, and one large cluster of these developmental genes is located on chromosome 12.

• The discovery of these genes was a stunning surprise with two lucky aspects to it.

• As the fertilized egg grows into an embryo, it gradually develops two asymmetries – a head-tail axis and a front-back axis. In mammals, these asymmetries develop later and nobody knows quite how.

•Jani Nusslein-Volhard and Eric Wieschaus found that there are ‘gap’ genes, ‘pair-rule’ genes, and ‘segment-polarity’ genes that act hierarchically to create detail in an embryo.

• They discovered a cluster of eight homeotic genes lying together on the same chromosome, which they called Hox genes.

• The Hox genes were lined up in the same order as the part of the fly they affected.

• They also discovered that all homeotic gene had a ‘paragraph’ of text within the gene – known as the homeobox – which was almost exactly 180 letters long.

•The discovery of mouse-fly homology implies that the mechanism of embryonic development requires the genes to be in the same order as the body parts.

• Mice have thirty-nine Hox genes altogether, in four clusters, and they have up to five extra Hox genes at the rear end of each cluster that flies do not have. Various genes are missing in each cluster.

• The practical application was that suddenly all those decades of hard work on the genes of fruit flies were now relevant to human beings.

• What is true of mice is just as true of people – Flies and people are just variations on a theme of how to build a body that was laid down in some worm-like creature in the Cambrian period. They still retain the same genes doing he same job.

“The exceptions are almost more convincing than the rule – for instance, in flies, there are two genes that are crucial to laying down the difference between the back (dorsal) of the body and the front (ventral). One, called decapentaplegic, is dorsalisng…”•Geneticists can now routinely mutate genes in flies and replace them with equivalent human genes.

• This technique is known as genetic rescue, and it allows for normal fly growth.

• The time of the Cambrian explosion was a moment of free experimentation in body design, similar to the mid-1980s computer software boom.

• Hox C4 is the genetic equivalent of a gene called dfd in flies, which is expressed in what will become the mouthparts of an adult fly.

• If you ‘knock out’ one of these genes by mutation, you find that one or two neck vertebrae are affected in mice.

•Hox and hedgehog genes were discovered to control development from dry bones of fossils.

• These findings were surprising to palaeontologists who read of embryologists’ discovery that this is how the Hox genes work.

• The Hox genes set up a gradient of expression to divide the limb into separate arm and wrist bones, then they suddenly set up a reverse gradient on the outside of the last bones to throw off the five digits.

"A gilded No is more satisfactory than a dry yes" - Gracian