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The first suggestion that chromosomes are the carriers of heredity was made by Walter Sutton in 1902, two years after Mendel’s work came to be widely known. Sutton hypothesized that chromosomes are composed of units (“genes”) that correspond to Mendelian factors, and showed that meiosis gives a mechanism for Mendelian inheritance. Sutton’s hypothesis was verified a few years later by Thomas Hunt Morgan via experiments on that hero of genetics, the fruit fly. However, the molecular makeup of genes, or how they produced physical traits in organisms, was still not known.

By the late 1920s, chemists had discovered both ribonucleic acid (RNA) and deoxyribonucleic acid (DNA), but the connection with genes was not discovered for several more years. It became known that chromosomes contained DNA, and some people suspected that this DNA might be the substrate of genes. Others thought that the substrate consisted of proteins found in the cell nucleus. DNA of course turned out to be the right answer, and this was finally determined experimentally by the mid-1940s.

But several big questions remained. How exactly does an organism’s DNA cause the organism to have particular traits, such as tall or dwarf stems? How does DNA create a near-exact copy of itself during cell division (mitosis)? And how does the variation, on which natural selection works, come about at the DNA level?

These questions were all answered, at least in part, within the next ten years. The biggest break came when, in 1953, James Watson and Francis Crick figured out that the structure of DNA is a double helix. In the early 1960s, the combined work of several scientists succeeded in breaking the genetic code—how the parts of DNA encode the amino acids that make up proteins. A gene—a concept that had been around since Mendel without any understanding of its molecular substrate—could now be defined as a substring of DNA that codes for a particular protein. Soon after this, it was worked out how the code was translated by the cell into proteins, how DNA makes copies of itself, and how variation arises via copying errors, externally caused mutations, and sexual recombination. This was clearly a “tipping point” in genetics research. The science of genetics was on a roll, and hasn’t stopped rolling yet.

The Mechanics of DNA

The collection of all of an organism’s physical traits—its phenotype—comes about largely due to the character of and interactions between proteins in cells. Proteins are long chains of molecules called amino acids.

Every cell in your body contains almost exactly the same complete DNA sequence, which is made up of a string of chemicals called nucleotides. Nucleotides contain chemicals called bases, which come in four varieties, called (for short) A, C, G, and T. In humans, strings of DNA are actually double strands of paired A, C, G, and T molecules. Due to chemical affinities, A always pairs with T, and C always pairs with G.

Sequences are usually written with one line of letters on the top, and the paired letters (base pairs) on the bottom, for example,

TCCGATT …

AGGCTAA …

In a DNA molecule, these double strands weave around one another in a double helix (figure 6.1).

Subsequences of DNA form genes. Roughly, each gene codes for a particular protein. It does that by coding for each of the amino acids that make up the protein. The way amino acids are coded is called the genetic code. The code is the same for almost every organism on Earth. Each amino acid corresponds to a triple of nucleotide bases. For example, the DNA triplet AAG corresponds to the amino acid phenylalanine, and the DNA triplet C A C corresponds to the amino acid valine. These triplets are called codons.

So how do proteins actually get formed by genes? Each cell has a complex set of molecular machinery that performs this task. The first step is transcription (figure 6.2), which happens in the cell nucleus. From a single strand of the DNA, an enzyme (an active protein) called RNA polymerase unwinds