The members of a gene family have a common organization

  • A superfamily is a set of genes all related by presumed descent from a common ancestor, but now showing considerable variation.
  • A common feature in a set of genes is assumed to identify a property that preceded their separation in evolution.
  • All globin genes have a common form of organization with 3 exons and 2 introns, suggesting that they are descended from a single ancestral gene.

A fascinating case of evolutionary conservation is presented by the α- and β-globins and two other proteins related to them. Myoglobin is a monomeric oxygen-binding protein of animals, whose amino acid sequence suggests a common (though ancient) origin with the globin subunits. Leghemoglobins are oxygen-binding proteins present in the legume class of plants; like myoglobin, they are monomeric. They too share a common origin with the other heme-binding proteins. Together, the globins, myoglobin, and leghemoglobin constitute the globin superfamily, a set of gene families all descended from some (distant) common ancestor.
Both α- and β-globin genes have three exons (see Figure 2.7). The two introns are located at constant positions relative to the coding sequence. The central exon represents the heme-binding domain of the globin chain.
Myoglobin is represented by a single gene in the human genome, whose structure is essentially the same as that of the globin genes. The three-exon structure therefore predates the evolution of separate myoglobin and globin functions.

Leghemoglobin genes contain three introns, the first and last of which occur at points in the coding sequence that are homologous to the locations of the two introns in the globin genes. This remarkable similarity suggests an exceedingly ancient origin for the heme-binding proteins in the form of a split gene, as illustrated in Figure 2.24.
The central intron of leghemoglobin separates two exons that together code for the sequence corresponding to the single central exon in globin. Could the central exon of the globin gene have been derived by a fusion of two central exons in the ancestral gene? Or is the single central exon the ancestral form; in this case, an intron must have been inserted into it at the start of plant evolution?

Cases in which homologous genes differ in structure may provide information about their evolution. An example is insulin. Mammals and birds have only one gene for insulin, except for the rodents, which have two genes. Figure 2.25 illustrates the structures of these genes.
The principle we use in comparing the organization of related genes in different species is that a common feature identifies a structure that predated the evolutionary separation of the two species. In chicken, the single insulin gene has two introns; one of the two rat genes has the same structure. The common structure implies that the ancestral insulin gene had two introns. However, the second rat gene has only one intron. It must have evolved by a gene duplication in rodents that was followed by the precise removal of one intron from one of the copies.
The organization of some genes shows extensive discrepancies between species. In these cases, there must have been extensive removal or insertion of introns during evolution.
A well characterized case is represented by the actin genes. The typical actin gene has a nontranslated leader of <100 bases, a coding region of ~1200 bases, and a trailer of ~200 bases. Most actin genes are interrupted; the positions of the introns can be aligned with regard to the coding sequence (except for a single intron sometimes found in the leader).

Figure 2.26 shows that almost every actin gene is different in its pattern of interruptions. Taking all the genes together, introns occur at 12 different sites. However, no individual gene has more than 6 introns; some genes have only one intron, and one is uninterrupted altogether. How did this situation arise? If we suppose that the primordial actin gene was interrupted, and all current actin genes are related to it by loss of introns, different introns have been lost in each evolutionary branch. Probably some introns have been lost entirely, so the primordial gene could well have had 20 or more. The alternative is to suppose that a process of intron insertion continued independently in the different lines of evolution. The relationships between the intron locations found in different species may be used ultimately to construct a tree for the evolution of the gene.
The relationship between exons and protein domains is somewhat erratic. In some cases there is a clear 1:1 relationship; in others no pattern is to be discerned. One possibility is that removal of introns has fused the adjacent exons. This means that the intron must have been precisely removed, without changing the integrity of the coding region. An alternative is that some introns arose by insertion into a coherent domain. Together with the variations that we see in exon placement in cases such as the actin genes, this argues that intron positions can be adjusted in the course of evolution.
The equation of at least some exons with protein domains, and the appearance of related exons in different proteins, leaves no doubt that the duplication and juxtaposition of exons has played an important role in evolution. It is possible that the number of ancestral exons, from which all proteins have been derived by duplication, variation, and recombination, could be relatively small (a few thousands or tens of thousands). By taking exons as the building blocks of evolution, this view implicitly accepts the introns early model for the origin of genes coding for proteins.

No comments:

Post a Comment