Cathryn of Bradford u3a
Sequencing the DNA Code
Sequencing the DNA Code
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When I was a biology undergraduate, we read the DNA code with a plastic ruler. First we had isolated some DNA, ran it on a gel, giving us a ‘ladder’ to ‘read’. We diligently wrote down the letters as we moved the ruler down a photo of the gel. CAGTACTGTTAACTA Then we translated that to an amino acid sequence and found what protein it came from. This is how the first genome was read and decoded, and we experienced what it was like for early pioneers. Later my own studies looked at the genetics of the myosin motor molecule, using different sized flies to see how the speed of the motor was changed by genetic changes. This helps us understand how small genetic changes can affect how muscles work.
From the clarification of DNA structure in the 1950s, to the first gene sequence in 1972, development has been rapid. With faster sequencing methods came the first genomes, first of simple organisms like worms and viruses, and the lab ‘rat’ the Drosophila fruit fly. We discovered that we share many of our genes with these simple creatures! The Human Genome Project produced a rough draft by 2003 using a ‘gene jumping’ method, but the enormity of the challenge is illustrated by the fact that it was not totally sequenced until 2022.
Why was it so important to sequence a genome?
Genomic analysis has revolutionised not just medicine, but agriculture and criminology. It has elucidated puzzles of history and prehistory, and even enabled, by genetic editing, back breeding to ancient type wolves. The phrase in common use ‘it’s in our DNA’ is used in all sorts of contexts not to do with DNA, embedding science in society.
Genetic diseases such as cystic fibrosis and muscular atrophy were identified long ago, but now gene editing gives us a means of giving people one off therapies for these debilitating disorders, instead of a life on pills. Other disorders treated by gene editing are inherited vision loss caused by a faulty retinal gene, and cancers, such as multiple myeloma and bladder cancer. Gene editing can fix some heart disease by inactivating a gene in the liver, and this prevents amyloidosis in the heart. Other genes targeted are involved in inherited high ‘bad’ cholesterol. For people with inherited diseases, which were a mystery in the past, gene therapy is a modern magic.
When covid broke out in Wuhan in early 2020, the Chinese lab made public the genome sequence so that labs all over the world could work on vaccines and develop them rapidly. Continuing analysis enables labs to track different mutations. Scientists also can study how variation in the body’s receptor for the virus, the ACE2 molecule, affects how people react to the covid virus.
Genetic modulation of plants and animals can be seen as an accelerated form of selective breeding, that we have been doing for millennia. One of the most successful and least controversial is ‘golden rice’ genetically modified to have more vitamin A, retinol. This has led to alleviation of terrible disease in Asia and Africa: blindness and death. More recent use of gene modification to make cows ‘fart’ less has been more controversial.
DNA ‘fingerprinting’ uses certain genetic variations to identify individuals. This can be used to find missing people, ascertain paternity, or confirm family relationships. This needs to be used with caution, as an unexpected result is not always welcome. Prenatal genetic testing also holds some difficult ethics, but can be used to help parents make hard decisions if their unborn child has severe disabilities.
Used in criminal cases, DNA has been crucial in thousands of cases of bringing culprits to justice, or ruling out the innocent, which is just as important. DNA evidence cannot be used on its own: there has to be other evidence corroborating it.
Our perception of what it is to be human has been radically transformed by the finding that in Europe we have very ancient Neanderthal DNA still in our genome. Analysis of ancient DNA has shown us how people migrated from Anatolia and later the Asian steppes across Europe to Britain. It has even allowed us to have an informed guess at what these people looked like. The first migrations were of light eyed, dark skinned people, later they were light skinned. The mutation for blue eyes is thought to be from about 6000 BC in the Caucasus. Some of these people migrated south into the Levant, so we see many Gazans with blue and green eyes.
DNA has thrown light on more recent historical puzzles. Richard the third’s skeleton found in a Leicester car park was matched to mitochondrial DNA passed down the female line from Cecily Neville. Analysis of y chromosome DNA showed that men descended by marriage from Richard’s uncles were not actually related to Richard: this means that at some point the women in the line had affairs with unknown fathers.
Czar Nicholas the second’s entire family was killed during the Russian Revolution in 1918. British experts helped to confirm the identity of the remains of the bodies of five of Czar Nicholas' family in 1994, but two children were missing, feeding rumours that one, Anastasia, had survived. After another grave was found in 2007 with two children, they were confirmed to be son Alexei, and one of his sisters. DNA samples from the children were matched to DNA from a bloodstained shirt of the Tsar from an assassination attempt, and to relatives of Queen Victoria. The DNA analysis was done as a collaboration between American, Russian and British scientists. Thus a 90 year mystery was finally solved.
Sequencing DNA has made the modern world we live in; its medicines, health and wellbeing, its foods. It has given us a window on the past, allowing us to understand our origins and our place in the world today. Of all human ‘inventions’ it has probably been the most benign and beneficial.
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https://www.genome.gov/human-genome-project gene editing https://pmc.ncbi.nlm.nih.gov/articles/PMC5131771/ https://royalsociety.org/news-resources/projects/gm-plants/what-is-gm-and-how-is-it-done/ https://le.ac.uk/richard-iii/identification/genetics/overview
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