Exons and Introns

The problem of genetic variability has been approached thus far considering the gene as a black box. Genes have also been described superficially as chunks of DNA. It is now possible to describe the structure of genes with greater precision.

Figure 1.11 presents a schematic view of a eukaryotic gene. The DNA molecule is organized in two major components, exons and introns. Exons are coding segments of DNA that are ultimately responsible for building proteins. Introns are noncoding sequences that intervene between exons. A particular gene can contain one or several exons mixed in tandem with introns. The entire gene is transcribed into RNA, but introns are eventually spliced, giving

Figure 1.11 Schematic representation of the various regions of a gene. The particular elements represented in the promoter region vary across genes. Some genes lack GC and CAAT elements, some lack the TATA element. Exons contain information useful for translation purposes, whereas introns include nontranslatable information. Both exons and introns are transcribed into premessenger RNA. Intron regions are excised and the remaining RNA is spliced to form mature mRNA, subsequently used as a template to build a protein.

rise to the mRNA used to build a protein. Transcription occurs from the 5' to the 3' end (“5-prime” and “3-prime” refer to the position of the carbon in the sugar rings where a phosphate and hydroxyl chemical groups attach, respectively). Toward the 5' end there is a promoter region, so called because the bases found there (GC, CAAT, and TATA boxes), which can vary across genes, control the initial binding of the RNA polymerase and the start point of transcription. The 3' end contains a stop codon signaling the termination of transcription.

It has been suggested that the crossing over of introns could lead to exon duplication and exchange between genes. The best evidence for such exon shuffling lies in the fact that most genes appear to be mosaics of other genes, rather than entirely novel nucleotide sequences. For example, the genes coding for the low-density lipoprotein and the epidermal growth factor have a homologous region consisting of 8 contiguous exons (105 to 228 base pairs). Five of the nine introns interrupt the sequence at precisely the same amino acid in these two genes. Such a degree of coincidence suggests that these two genes derive from a common ancestral gene.

Exon shuffling would lead to genetic variability at a much faster rate than that of mutations (see later in this section). In addition, the exon-intron arrangement can allow for greater phenotypic plasticity, as has been shown to be the case for the immune system (Langman, 1989). For example, genes coding for antigen-specific binding regions in higher vertebrates are typically formed by a constant exon attached to several variable exons. These exons are separated by introns which, during RNA splicing, allow for the formation of a variety of mRNA combinations between the constant exon and any of the variable exons. Antibodies formed in this manner, called rearranging immunoglobulins, can deal with an enormous variety of pathogens.