Concerted Evolution in Multigene Families
In a multigene family, complete identity is often maintained among multiple copies arranged in a tandem array. Sometimes, this identity is observed even among repeats located on different chromosomes. For instance, multiple copies of r-DNA repeats, located on a single nucleolar organizing region (NOR) of a satellited chromosome, have been shown to have complete identity in a wide range of organisms. However, there are reports, where identical rDNA repeat units were found on two different NORs (located on two different human chromosomes). Similarly, in yeast, eight identical tyrosine iRNA genes are located on eight different chromosomes, although their flanking sequences differ. This suggests that individual members of a gene family can not evolve independently; instead, they undergo a concerted evolution, meaning that multiple copies of a multigene family evolve as a single unit. One may like to know the basis of this concerted evolution. In fact, when a large number of copies of the same gene are present, mutation in one or more copies will not have any significant effect on the fitness of the organism, so that such mutations can not be eliminated by natural selection; instead we should expect that mutations, particularly those which are neutral, should accumulate in course of time.
Contrary to this expectation, homogeneity is maintained, which has been considered to be a paradox that needs explanation. Attempts have been made to suggest possible mechanisms that may lead to homogeneity among members of a multigene family. Experimental and circumstantial evidence is also available for the existence of such a homogenizing mechanism. One such evidence suggesting the presence of homogenizing mechanism, is the association of a 'coding sequence' with a 'spacer region' in each member of a multigene family. There may be reasons for conservation of coding and regulatory sequences due to identical function of different repeat units, but homogenization of spacer region can not be explained on the basis of any selection pressure. Instead, it is explained on the basis of their cohomogenization along with the selectable coding sequences. Another more compelling evidence suggesting the presence of homogenizing mechanism is available in yeast. In this case, a sequence located between rRNA transcriptional units of adjoining repeats, has been shown to stimulate localized recombination. These recom-binational hot spots are believed to ensure homogenization by promoting any one of the following three phenomena : (i) gene conversion, (ii) unequal sister chromatid exchange and (iii) gene amplification.
The phenomenon of gene conversion was earlier discussed in Tetrad Analysis, Mitotic Recombination and Gene Conversion in Haploid Organisms (Fungi and Single Celled Algae)
and Molecular Mechanisms of Recombination
and involves non-reciprocal recombination events. In a multigene family, if a mutant copy is found, it may pair with a wild type copy forming a heteroduplex (hybrid DNA). The heteroduplex undergoes repair, so that one gene copy is corrected with respect to the other leading to homogenization. Such a mechanism can also explain maintenance of homogeneity in a dispersed multigene family, where genes are not arranged in a tandem array.
Sister chromatid exchange
This is another unusual recombination event, which may lead to homogenization^ In this mechanism, after replication, the two identical tendem arrays (having a mutant copy) located on sister chromatids, pair out of register (compare with unequal crossing over at Bar
locus in Drosophila,
discussed in Fine Structure of Gene-at the Genetic Level (A New Concept of Allelomorphism)
) and undergo recombination. This leads to loss of the mutant copy in one chromatid and its duplication in the other. Such repeated events will lead to homogenization.
When a mutant copy is present in a multigene family, spontaneous amplification of either the functional or the non-functional mutant copy may take place. When the amplification involves functional copy, the mutant may spread, but when it involves non-functional copy, the individual may die and get eliminated. In either case it will lead to homogenization.