We begin this chapter with a look at how the genetic code was broken (deciphered). The very terms genetic code, broken and deciphered came from what was at the time, the recent history of the World War II. Winning WWII relied heavily on breaking enemy codes (recall the Enigma machine), and hiding strategic battle information from the enemy (recall the Navajo code talkers). We will look at the elegant experiments that first deciphered the amino acid meaning of a few 3-base codons, and then all 64 codons. Of these, 61 encode amino acids and three are stop codons. The same kinds of experiments that broke the genetic code also led to our under-standing of the mechanism of protein synthesis. Early studies indicated that genes and proteins are colinear, i.e., that the length of a gene was directly proportional to the polypeptide it encoded. It would follow then, that the lengths of mRNAs are also collinear with their translation products.
Colinearity suggested the obvious hypotheses that translation proceeded in three steps (initiation, elongation and termination), just like transcription itself. We now know that initiation is a complex process involving the assembly of a translation machine near the 5’ end of the mRNA. This machine consists of ribosomes, mRNA, several initiation factors and a source of chemical energy. Since mature mRNAs are actually longer than needed to specify a polypeptide (even after splicing!), one function of initiation factors is to position the ribosome and associated proteins near a start codon. The start codon specifies the first amino acid in a new polypeptide. Once the initiation complex forms, elongation begins. Cycles of condensation reactions on the ribosome connect amino acids by peptide linkages, growing the chain from its amino-end to its carboxyl-end. Translation ends when the ribosome moving along the mRNA encounters a stop codon. We will look at how we came to understand the discrete steps of translation.
Learning ObjectivesWhen you have mastered the information in this chapter, you should be able to:
1. Compare and contrast the mechanisms and energetics of initiation, elongation and termination of translation and transcription.
2. Speculate on why the genetic code is universal (or nearly so).
3. Justify early thinking about a 4-base genetic code.
4. Justify early thinking about an overlapping genetic code (for example, one in which the last base of a codon could be the first base of the next codon in an mRNA.
5. Explain why all tRNA structures share some, but not other features.
6. Compare and Contrast the roles of ribosomal A, E and P sites in translation.
7. Trace the formation of an aminoacyl-tRNA and the bacterial Initiation Complex.
8. Describe the steps of translation that require chemical energy.
9. Formulate an hypothesis to explain why stop codons all begin with U.
10. Create a set of rules for inferring an amino acid sequence from a stretch of DNA sequence.
11. Speculate about why large eukaryotic genomes encode so few proteins.