In a schoolyard game, a verbal message, such as “John’s brown dog ran away from home,” is whispered to a child, who runs to a second child and repeats the message. The message is relayed from child to child around the schoolyard until it returns to the original sender. Inevitably, the last child returns with an amazingly transformed message, such as “Joe Brown has a pig living under his porch.” The larger the number of children playing the game, the more garbled the message becomes. This game illustrates an important principle: errors arise whenever information is copied; the more times it is copied, the greater the potential number of errors.
A complex, multicellular organism faces a problem analogous to that of the children in the schoolyard game: how to faithfully transmit genetic instructions each time that its cells divide. The solution to this problem is central to replication. A single-celled human zygote contains 6.4 billion base pairs of DNA; even a low rate of error during copying, such as once per million base pairs, would result in 6400 mistakes made every time a cell divided—errors that would be compounded at each of the millions of cell divisions that take place in human development.
Not only must the copying of DNA be astoundingly accurate, it must also take place at breakneck speed. The single circular chromosome of E. coli contains about 4.6 million base pairs. At a rate of more than 1000 nucleotides per minute, replication of the entire chromosome would require almost three days. Yet, as already stated, these bacteria are capable of dividing every 20 minutes. Escherichia coli actually replicates its DNA at a rate of 1000 nucleotides per second, with less than one error in a billion nucleotides. How is this extraordinarily accurate and rapid process accomplished?