The Genetic Code
OVERVIEW OF TRANSLATIONThe second stage in gene expression is translating the nucleotide sequence of a messenger RNA molecule into the amino acid sequence of a protein. The genetic code is defined as the relationship between the sequence of nucleotides in DNA (or its RNA transcripts) and the sequence of amino acids in a protein. Each amino acid is specified by one or more nucleotide triplets (codons) in the DNA. During translation, mRNA acts as a working copy of the gene in which the codons for each amino acid in the protein have been transcribed from DNA to mRNA. tRNAs serve as adapter molecules that couple the codons in mRNA with the amino acids they each specify, thus aligning them in the appropriate sequence before peptide bond formation. Translation takes place on ribosomes, complexes of protein and rRNA that serve as the molecular machines coordinating the interactions between mRNA, tRNA, the enzymes, and the protein factors required for protein synthesis. Many proteins undergo posttranslational modifications as they prepare to assume their ultimate roles in the cell.
THE GENETIC CODE
Most genetic code tables designate the codons for amino acids as mRNA sequences. Important features of the genetic code include:
• Each codon consists of three bases (triplet). There are 64 codons. They are all written in the 5' to 3' direction.
• 61 codons code for amino acids. The other three (UAA, UGA, UAG) are stop codons (or nonsense codons) that terminate translation.
• There is one start codon (initiation codon) , AUG, coding for methionine. Protein synthesis begins with methionine (Met) in eukaryotes, and formylmethionine (fmet) in prokaryotes.
• The code is unambiguous. Each codon specifies no more than one amino acid.
• The code is degenerate. More than one codon can specify a single amino acid. All amino acids, except Met and tryptophan (Trp ), have more than one codon.
• For those amino acids having more than one codon, the first two bases in the codon are usually the same. The base in the third position often vanes.
• The code is universal (the same in all organisms) . Some minor exceptions to this occur in mitochondria.
• The code is commaless (contiguous) . There are no spacers or "commas" between codons on an mRNA.
• Neighboring codons on a message are nonoverlapping.
Mutations
A mutation is any permanent, heritable change in the DNA base sequence of anorganism. This altered DNA sequence can be reflected by changes in the base sequence of mRNA, and, sometimes, by changes in the amino acid sequence of
a protein. Mutations can cause genetic diseases. They can also cause changes in enzyme activity, nutritional requirements, antibiotic susceptibility, morphology,
antigenicity, and many other properties of cells. A very common type of mutation is a single base alteration or point mutation.
• A transition is a point mutation that replaces a purine-pyrimidine base pair with a different purine-pyrimidine base pair. For example, an A-T base pair becomes a G-C base pair.
• A transversion is a point mutation that replaces a purine-pyrimidine base pair with a pyrimidine-purine base pair. For example, an A-T base pair becomes a T-A or a C-G base pair.
Mutations are often classified according to the effect they have on the structure
of the gene's protein product. This change in protein structure can be predicted
using the genetic code table in conjunction with the base sequence of DNA or
mRNA. A variety of such mutations is mentioned. Point mutations and frameshifts are illustrated in more detail.
Large Segment Deletions
Large segments of DNA can be deleted from a chromosome during an unequal
crossover in meiosis. Crossover or recombination between homologous chromosomes
is a normal part of meiosis I that generates genetic diversity in reproductive
cells (egg and sperm), a largely beneficial result. In a normal crossover
event, the homologous maternal and paternal chromosomes exchange equivalent
segments, and although the resultant chromosomes are mosaics of maternal
and paternal alleles, no genetic information has been lost from either one. On
rare occasions, a crossover can be unequal and one of the two homologs loses
some of its genetic information.
a-thalassemia is a well-known example of a genetic disease in which unequal
crossover has deleted one or more a-globin genes from chromosome 16. Cri-duchat
(mental retardation, microcephaly, wide-set eyes, and a characteristic kittenlike
cry) results from a terminal deletion of the short arm of chromosome 5.
Mutations in Splice Sites
Mutations in splice sites affect the accuracy of intron removal from hnRNA
during posttranscriptional processing. If a splice site is lost through mutation,
spliceosomes may:
• Delete nucleotides from the adjacent exon.
• Leave nucleotides of the intron in the processed mRNA.
• Use the next normal upstream or downstream splice site, deleting an
exon from the processed mRNA.
Mutations in splice sites have now been documented in many different diseases,
including B-thalassemia, Gaucher disease, and Tay-Sachs.