How to Build a Human: Adventures in How We Are Made and Who We Are. Philip Ball

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       The double helix of DNA. This iconic image creates a somewhat misleading picture, since for most of the time DNA in a cell’s chromosomes is packaged up quite densely in chromatin, in which it is wrapped around proteins called histones like thread on a bobbin. The “rungs” of the double-helical ladder consist of pairs of so-called nucleotide bases (denoted A, T, C and G) with shapes that complement each other and fit together well.

      So beautiful, indeed, was this molecular architecture and the story it seemed to disclose that modern biology was largely seduced by it. It was immediately obvious to Watson and Crick how heredity could be enacted on the molecular scale. The information in genes could be replicated by unzipping the double helix so that each strand could act as the template on which replicas could be assembled.⁷ Here, then, was how genetic information could be copied into new chromosomes when cells divide: a molecular-scale mechanism for the inheritance described by Mendel and Darwin, which Morgan and others had situated on the chromosomes. DNA married genetics with inheritance at the molecular level, bringing coherence to biology.

      And Darwinian evolution? If genes govern an organism’s traits, then random copying errors in DNA replication could alter a trait, mostly to the detriment of an organism but occasionally to its advantage. This is the variation on which natural selection acts to make organisms adapted to their environment.

      It all seemed to fall into place. All the important questions – about evolution, genetic disease, development – might now be answered by referring to the information in the genome. Cells didn’t seem to be a very important part of the story except as vehicles for genes and as machines for enacting their commands.

      To speak of information being “encoded” in DNA is to speak literally. Genes deploy a code: the genetic code. But what exactly do genes encode? On the most part, it is the chemical structure of a protein molecule, typically an enzyme. Because of the ways in which different amino acids “feel” one another and interact with the watery solvent all around them in the cell, a particular sequence of amino acids determines the way most protein chains fold up into a compact three-dimensional shape. This shape enables enzymes to carry out particular chemical transformations in the cell: they are catalysts that facilitate the cell’s chemistry. So the protein’s sequence, encoded in the respective gene, dictates its function.

      A protein’s amino-acid sequence is represented in its gene by the sequence of chemical constituents that make up DNA. There are four of these, called nucleotide bases and denoted by the labels A, T, G and C. Different triplets of bases represent particular amino acids in the resultant protein: AAA, for example, corresponds to the amino acid called lysine.

      Turning a gene into its corresponding protein is a two step-process. First, the gene on a piece of DNA in a chromosome is used as a template for building a molecule of another kind of nucleic acid, called RNA. This is called transcription. The piece of RNA made from a gene is then used as a template for putting the protein together, one amino acid at a time. This is called translation, and it is performed by a complex piece of molecular machinery called the ribosome, made of proteins and other pieces of RNA.

      Chromosomes consist of lengths of DNA double-helix wound around disk-like protein molecules called histones, like the string on a yoyo. This combination of DNA and its protein packaging is what we call chromatin. The genomes of eukaryotes are divided up into a number of chromosomes that is always the same for every cell of a particular species (if they are not abnormal) but can differ between species. Human cells have 46 chromosomes, in sets of 23 pairs.

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      It’s common to see genes called the instructions to make an organism. In this view, the entire genome is then the “instruction booklet”, or even the “blueprint”. This is an understandable metaphor, but misleading. Genes are fundamental to the way an organism turns out: the genome of a frog egg guides it to become a frog, not an elephant, and vice versa. But the way genes influence and to some degree dictate that proliferation of cells is subtle, complex, and resistant to any convenient metaphors from the technological world of design and construction. By leaping from genome to finished organism without taking into account the process of development from cells, we risk simplifying biology in ways that can create some deep misconceptions about how life proceeds and evolves.

      To the extent that a gene is an “instruction”, it is an instruction to build a protein molecule. It is far from obvious what, in general, this has to do with the growth and form of an organism: with the generation of our flesh. We know of no way to map an organism’s complement of proteins onto its shape, traits and behaviour: its phenotype. The two are worlds apart: it’s rather like trying to understand the meaning of a Dickens novel from a close consideration of the shapes of its letters and the correlations in their order of appearance.

      Besides, this conventional “blueprint” description of what genomes do is too simplistic even if we consider only how they dictate that roster of proteins. Here are some reasons why:

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