Primer
‘Explanations must be as simple as possible – and no simpler.’ Albert Einstein
LIFE IS WRITTEN IN FOUR LETTERS
THE LETTERS ARE A, C, G, T
The ‘Human Genome’ is the genetic code - the entire list of three billion letters - required to create a human being.
The instructions are encoded in DNA.
The four letters in the DNA alphabet – A, C, G, T - carry the instructions to make all living organisms.
The meaning of the code lies in the sequence of the letters.
All the instructions needed to make a human being are written in just these four letters.
‘A genome is an organism’s complete genetic signature; it is the palate of information an organism can call on in order to ensure its own survival and growth. The genome is the collection of information that an organism can pass on to its offspring before birth.’ De-mystifying Genomics, Medical Research Council, UK
‘The language of the genes has a simple alphabet, not with 26 letters but just four. These are the four different DNA bases…(A,G,C and T for short). The bases are arranged in words of three letters such as CGA or TGG… It is possible to write a meaningful sentence with 25 letters instead of 26, but only just. Life manages with a mere four.’ Steven Jones, Professor of Gentics, University College London, The Language of Genes, Harper Collins, 1993
‘An organism's genome is a two-dimensional and static description of a living creature. To come to life it must be translated into action, rather like a screenplay must be turned into acting. Genes in the nucleus of a cell act as the starting templates in a process that eventually leads to the production of proteins. These sophisticated molecules perform specific tasks, or get together with each other to make larger structures. Many proteins interact, for example, to liberate the energy a cell requires to function. In its complexity and simplicity, life is a dance of proteins.’ BBC, UK, 2003
“The total human sequence is the Grail of human genetics." Walter Gilbert, Nobel Laureate, Science, 1986
The Human Genome
There are three billion letters in the Human Genome.
Written out, the Human Genome would stretch 5,592 miles, (9,000 km).
It would take a typist working eight hours a day half a century to type.
It would fill one million pages; 5,000 books stacked 200 feet high; or two hundred telephone directories.
Read out for 24 hours a day, it would take a century to finish.
The human body has 100 trillion (100 000 000 000 000) cells – each contains a copy of the entire Genome.
At latest belief, the Human Genome contains around 20-25,000 genes.
It has taken scientists 13 years to decipher.
The Human Genome Project involved hundreds of scientists from the UK, China, Germany, Japan and the US in a global international effort; the UK was the largest contributor to the project, with one third sequenced at the Wellcome Trust’s Sanger Institute.
The Human Genome is 97% ‘junk DNA’, the purpose of which is mostly unknown; the Human Genome Project also sequenced this DNA in the hope of future elucidation – it is already becoming clear it has functionality and is wrongly named.
Every person on Earth shares 99.9% of the same genetic code; only 0.1% of our genetic makeup differs.
"The sequence of the human genome would be perhaps the most powerful tool ever developed to explore the mysteries of human development and disease." Leroy Hood, Issues in Science and Technology, 1987
"Biology will never be the same." John Sulston, Leader, UK Human Genome Project, interview with E. Pennisi, 2000
‘According to the most recent estimates, the number of human genes is possibly - but not certainly - between 20,000 and 25,000.’ Nature, 2005
COMPARATIVE GENOMICS
“Comparative genomics is going to be the single most important tool going forward in analysing genomes.” Dr John Sulston, Leader, UK Human Genome Project, UK
“Although we like to think we are special, our genes bring us down to Earth. DNA is what ties the entire living world together. It may well account for the extraordinary diversity among organisms but it also serves to underline their common origins - we all evolved from the same soup of chemicals... By studying non-human genomes, we gain insight into our own.” Monise Durrani, BBC Science
‘One of the most powerful general approaches for unlocking the secrets of the human genome is comparative genomics, and one of the most powerful starting points for comparison is the laboratory mouse, Mus musculus.’ Nature magazine, 2003
Mouse and man share 99% genetic similarity - including the genes to make a tail.
Humans and mice shared a common ancestor about 100 million years ago.
A mouse has about the same number of genes as a man.
Due to preserved genetic similarities, even after 530 million years of separation, introduced human genes can operate within the Fruit Fly genome.
The nematode worm shares many genes with human beings, including the genes to make muscle.
Puffer fish and Zebra fish are so genetically similar to human beings that their genomes are being deciphered as ‘model’ organisms for research.
The California purple sea urchin (Strongylocentrotus purpuratus) genome has 23,300 genes, of which 7077 are shared with human beings.
The dog genome also reveals many shared genes and diseases with humans; about 94% of the dog genome shows conserved synteny with mice, rats and humans.
Birds and human beings have three very similar genes affecting blunt limb buds.
Genetic similarity between humans and chimpanzees is between 96% and 99.4%
‘LUCA’, the ‘Last Universal Common Ancestor’ existed around four billion years ago. We are probably descended from a mud-burrowing worm.
The common ancestor of all placental mammals was probably a small nocturnal shrew-like creature, snuffling about more than 80 million years ago.
Dogs, goldfish, and ferns have more chromosomes than human beings.
75% of our genetic make-up is the same as a pumpkin - 57% the same as a cabbage.
The split between plants and animals occurred about 1.6 billion years ago.
Around 100 genes in flowering plant Arabidopsis thaliana (Thale Cress) are closely related to human disease genes; and Arabidopsis has most of its genes in common with all other plants on Earth.
‘A complete elucidation of genome function requires a parallel understanding of the sequence differences across species and the fundamental processes that have sculpted their genomes into the modern-day forms.’ US National Human Genome Research Institute, 2003
“This again reminds us of the unity of life - the fact that genes are not purpose-made for each organism, but rather evolution keeps on re-using its inventions over time.” Sir John Sulston, Director, Sanger Institute, UK
‘A corollary of the highest importance may be deducted from the foregoing remarks, namely, that the structure of every organic being is related to the most essential yet often hidden manner, to that of all other organic beings.’ Charles Darwin, The Origin of Species, 1859
‘One almost wonders what, other than genes that make humans embark on sequencing genomes, does set us apart from flies and worms..’. European Journal of Human Genetics, 2005
DNA
‘The most famous breakthrough in modern science was the discovery of the structure of DNA – the genetic material of all organisms in nature.’ Faber Book of Science, Ed John Carey, 2005
‘We have not ducked the technical language. Technical terms describe entitites and phenomena that simply do not exist in everyday life and, unless we employ those terms, we cannot refer, clearly, to the essential elements of the story. So we will explain what the terms mean, and then use them.’ Ian Wilmut, The Second Creation, Headline, 2001
DNA stands for deoxyribonucleic acid. (Much easier to say ‘DNA’.)
DNA is beautiful; shaped like an aesthetically pleasing, elegantly twisting spiral ladder - the ‘Double Helix’.
The structure of DNA was not elucidated until 1953.
DNA is a code which uses only four letters – A, C, G, T.
The letters stand for adenine, cytosine, guanine, thymine.
The DNA code uses groups of three letter words to make meaning.
There is 1.8 metres of DNA in each of our cells, packed into a structure less than a tenth of a millimetre across - leaving plenty of room on the head of a pin for angels.
Dazzlingly, if all the DNA in the human body was put end to end, it would reach to the Sun and back 600 times.
The rungs of the DNA ladder are ‘base pairs’ - adenine (A) bonds with thymine (T), cytosine (C) bonds with guanine (G). These can break apart, allowing the sides of the helix to unravel and DNA to magically copy itself.
Our genetic code consists of three billion DNA letters wound into 23 distinct bundles - chromosomes. Chromosomes means ‘coloured bodies’.
Each human parent passes on 23 chromosomes to their offspring, which pair to make 46 chromosomes in most human cells.
Each DNA sequence that can be used by cells to make a protein is called a ‘gene’. Proteins carry out most of the active functions of a cell. These sophisticated molecules build and maintain our bodies.
Proteins have a 20 letter language. The ingredients of a protein are amino acids. There are 20 different types of amino acids, meaning many different protein chains can be built. As for DNA, amino acids have a code letter.
Every human being on the planet shares 99.99% of the same genetic code.
DNA in the Human Genome libraries is gathered from male sperm and female blood.
‘As the earth and ocean were probably peopled with vegetable productions long before the existence of animals; and many families of these animals long before other families of them, shall we conjecture that one and the same kind of living filaments is and has been the cause of all organic life?’ Erasmus Darwin (grandfather of Charles), Zoonomia or the Laws of Organic Life, 1794
“We’ve discovered the secret of life.” Francis Crick, Co-discoverer of the structure of DNA, in local pub, 1953
‘Transcription - The cell makes a copy of the gene. The copy is made of RNA, a chemical similar to DNA. This is called ‘Messenger DNA’ which is edited, then translated by a ribosome. In turn, it translates each three letter word into the language of amino acids to make proteins.’ YourGenome.org
“So although there are only twenty or so amino acids, the range of proteins to which they can give rise is effectively infinite. In the same way the twenty-six letters of the western alphabet can code the language of Shakespeare, and 10,000 other languages as well.” Ian Wilmut, scientist
‘DNA makes RNA makes protein!’ Francis Crick, Co-discoverer of the structure of DNA
“In principle the duplication of DNA is straightforward, yet in execution it is miraculous, although it happens millions of times each second, in each of us… DNA, RNA, and protein are indeed the trinity on which all life on Earth is based.” Ian Wilmut, scientist
‘The more we learn about what's in the 'junk', the more it seems better to call it 'noncoding' DNA' instead.’ Yourgenome.org
‘We are made of stardust.’ John Gribbin, Stardust: the cosmic recycling of stars, planets and people, Penguin, 2001
‘The poem... is a little myth of man's capacity of making life meaningful. And in the end, the poem is not a thing we see - it is, rather, a light by which we may see - and what we see is life.’ Robert Penn Warren, Saturday Review, 1958
The Human Genome is a book that can read itself
The Human Genome is a book that can read itself - transcribing genes, copying, editing, translating. DNA copied into Messenger RNA…Transfer RNA – genes to acids to proteins. Codes and symbols becoming hair and teeth - skin, wings, kisses. A magical factory of words and chemicals still writing and editing itself after four billion years of Evolution. Letter, word, language, message and dictionary, understood by all living things - bird to man, lizard to man, fish to man. Fly, tiger, owl, worm and Polar Bear. That being heard makes hands and eyes; fur, claw, egg and tongue - reading themselves into existence. It is the book of life. A book that wrote itself. That writes itself; is writing, always. A book where the author is at once the book. In sublime biological creativity, it is the poetry of existence. The art of chemistry. Potential, script and means of organic expression; of life. The calling and creation of materials out of darkness. The Human Genome is a poem.
‘In a sense, human flesh is made of stardust.’ Nigel Calder, the Key to the Universe, BBC, 1977
‘Looking back from the present, the genome seems immortal. An unbroken chain of descent links the very first ur-gene with the genes active in your body now – an unbroken chain of perhaps fifty billion copyings over four billion years.’ Matt Ridley, Genome: The Autobiography of a Species in 23 Chapters, Fourth Estate, 2000
