13. Summary

4.13 Summary

Almost all genes belong to families, defined by the possession of related sequences in the exons of individual members. Families evolve by the duplication of a gene (or genes), followed by divergence between the copies. Some copies suffer inactivating mutations and become pseudogenes that no longer have any function. Pseudogenes also may be generated as DNA copies of the mRNA sequences.

An evolving set of genes may remain together in a cluster or may be dispersed to new locations by chromosomal rearrangement. The organization of existing clusters can sometimes be used to infer the series of events that has occurred. These events act with regard to sequence rather than function, and therefore include pseudogenes as well as active genes.

Mutations accumulate more rapidly in silent sites than in replacement sites (which affect the amino acid sequence). The rate of divergence at replacement sites can be used to establish a clock, calibrated in percent divergence per million years. The clock can then be used to calculate the time of divergence between any two members of the family.

A tandem cluster consists of many copies of a repeating unit that includes the transcribed sequence(s) and a nontranscribed spacer(s). rRNA gene clusters code only for a single rRNA precursor. Maintenance of active genes in clusters depends on mechanisms such as gene conversion or unequal crossing-over that cause mutations to spread through the cluster, so that they become exposed to evolutionary pressure.

Satellite DNA consists of very short sequences repeated many times in tandem. Its distinct centrifugation properties reflect its biased base composition. Satellite DNA is concentrated in centromeric heterochromatin, but its function (if any) is unknown. The individual repeating units of arthropod satellites are identical. Those of mammalian satellites are related, and can be organized into a hierarchy reflecting the evolution of the satellite by the amplification and divergence of randomly chosen sequences.

Unequal crossing-over appears to have been a major determinant of satellite DNA organization. Crossover fixation explains the ability of variants to spread through a cluster. Minisatellites have properties similar to satellites, but are much smaller; they are useful for human genomic mapping.