Exon sequences are conserved but introns vary

KEY CONCEPTS:

• Comparisons of related genes in different species show that the sequences of the corresponding exons are usually conserved but the sequences of the introns are much less well related.
• Introns evolve much more rapidly than exons because of the lack of selective pressure to produce a protein with a useful sequence.

Is a structural gene unique in its genome? The answer can be ambiguous. The entire length of the gene is unique as such, but its exons often are related to those of other genes. As a general rule, when two genes are related, the relationship between their exons is closer than the relationship between the introns. In an extreme case, the exons of two genes may code for the same protein sequence, but the introns may be different. This implies that the two genes originated by a duplication of some common ancestral gene. Then differences accumulated between the copies, but they were restricted in the exons by the need to code for protein functions.

As we see later when we consider the evolution of the gene, exons can be considered as basic building blocks that are assembled in various combinations. A gene may have some exons that are related to exons of another gene, but the other exons may be unrelated. Usually the introns are not related at all in such cases. Such genes may arise by duplication and translocation of individual exons.

The relationship between two genes can be plotted in the form of the dot matrix comparison of Figure 2.9. A dot is placed to indicate each position at which the same sequence is found in each gene. The dots form a line at an angle of 45° if two sequences are identical. The line is broken by regions that lack similarity, and it is displaced laterally or vertically by deletions or insertions in one sequence relative to the other.

When the two β-globin genes of the mouse are compared, such a line extends through the three exons and through the small intron. The line peters out in the flanking regions and in the large intron. This is a typical pattern, in which coding sequences are well related, the relationship can extend beyond the boundaries of the exons, but it is lost in longer introns and the regions on either side of the gene.

The overall degree of divergence between two exons is related to the differences between the proteins. It is caused mostly by base substitutions. In the translated regions, the exons are under the constraint of needing to code for amino acid sequences, so they are limited in their potential to change sequence. Many of the changes do not affect codon meanings, because they change one codon into another that represents the same amino acid. Changes occur more freely in nontranslated regions (corresponding to the 5 leader and 3 trailer of the mRNA).

In corresponding introns, the pattern of divergence involves both changes in size (due to deletions and insertions) and base substitutions. Introns evolve much more rapidly than exons. When a gene is compared in different species, sometimes the exons are homologous, while the introns have diverged so much that corresponding sequences cannot be recognized.

Mutations occur at the same rate in both exons and introns, but are removed more effectively from the exons by adverse selection. However, in the absence of the constraints imposed by a coding function, an intron is able quite freely to accumulate point substitutions and other changes. These changes imply that the intron does not have a sequence-specific function. Whether its presence is at all necessary for gene function is not clear.