Molecular Basis of Inheritance

Mendel's "factors" that carry traits are now known to be made of a molecule called DNA (deoxyribonucleic acid). DNA is the genetic material in almost all living things — it stores the instructions to build and run the organism and passes them from parents to offspring. (In a few viruses the genetic material is RNA.)

DNA is a long polymer of units called nucleotides. Each nucleotide has three parts: a nitrogenous base, a deoxyribose sugar and a phosphate group. There are four bases: adenine (A), thymine (T), guanine (G) and cytosine (C).

Watson and Crick (1953) worked out that DNA is a double helix — two strands twisted around each other like a spiral staircase. Key features:

• The two strands run in opposite directions (antiparallel) and are held together by the bases pairing in the middle.
• The base pairing is specific: A always pairs with T, and G always pairs with C (joined by hydrogen bonds). This is complementary base pairing.
• Because of this rule, the two strands are complementary: knowing the order of bases on one strand tells you the order on the other.

This neat structure explains how DNA can store information (in the sequence of bases) and how it can be copied accurately.

Before a cell divides, its DNA must be copied so each daughter cell gets a full set of instructions. This copying is DNA replication. The double helix "unzips" as the two strands separate, and each old strand acts as a template on which a new complementary strand is built (following A–T, G–C pairing), with the help of the enzyme DNA polymerase. The result is two identical DNA molecules, each having one old strand and one new strand. Because half of each new molecule is conserved from the parent, replication is called semi-conservative.

How does DNA actually control the cell? Through the central dogma of molecular biology, the flow of genetic information:

DNA → RNA → Protein

• Transcription — the information in a gene (a stretch of DNA) is copied into a molecule of messenger RNA (mRNA). RNA is single-stranded, has ribose sugar, and uses the base uracil (U) in place of thymine.
• Translation — the mRNA carries the message to the ribosomes, where it is "read" to join amino acids in the correct order to build a protein.

So genes work by directing the making of proteins, and proteins carry out the cell's functions and build its structures. This is how the information stored in DNA is finally turned into the features of the organism.

How does the four-letter language of DNA (A, T, G, C) specify the twenty kinds of amino acids in proteins? Through the genetic code. The bases are read in groups of three, and each triplet of bases on the mRNA is called a codon. Each codon stands for one amino acid — for example, the codon AUG codes for the amino acid methionine and also acts as the "start" signal. A few codons are "stop" signals that end the protein.

Important features of the genetic code:

• It is a triplet code (three bases per codon).
• It is universal — almost the same in all organisms, from bacteria to humans, which is strong evidence that all life shares a common origin.
• It is degenerate — most amino acids are coded by more than one codon.
• It is non-overlapping and read in a fixed direction.

A gene is a segment of DNA that carries the code for one protein (or RNA). A change in the DNA sequence is a mutation; mutations create variation, and some cause disease (for example, a single base change causes sickle-cell anaemia).

The complete set of an organism's DNA is its genome. The Human Genome Project (completed 2003) mapped the entire human genome — about 3 billion base pairs and some 20,000–25,000 genes. Such knowledge, and tools like DNA fingerprinting (which uses unique patterns in a person's DNA), are now used in medicine, forensics (solving crimes, identifying people) and the study of evolution.

How did scientists prove that DNA (and not protein) is the genetic material? Through a series of classic experiments:

• Griffith's experiment — working with Streptococcus pneumoniae bacteria, Griffith found that a harmless strain could be made deadly by something passed from heat-killed virulent bacteria. He called it the "transforming principle" (the process is transformation), though he did not know it was DNA.
• Avery, MacLeod and McCarty — they purified the transforming principle and showed it was DNA, because destroying DNA (not protein) stopped transformation.
• Hershey and Chase — using bacteriophages (viruses that infect bacteria) with radioactively labelled DNA and protein, they showed that only the DNA entered the bacteria, finally confirming DNA as the genetic material.

Studying DNA's chemistry, Chargaff's rule states that in any DNA the amount of adenine equals thymine (A = T) and guanine equals cytosine (G = C). This base-pairing equivalence supported the Watson–Crick double-helix model.

Genes are not all switched on all the time; their activity is controlled by gene regulation. In bacteria this is explained by the operon concept — a group of genes controlled together by a switch. The classic example is the lac operon of E. coli (described by Jacob and Monod): the genes that digest lactose are normally switched off, and are turned on only when lactose is present. This lets the cell make the digesting enzymes only when they are needed, saving energy.