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Unequal crossover generates variation in ubiquitin coding unit number at the human UbC polyubiquitin locus.

An observed mRNA length polymorphism of the human UbC polyubiquitin gene transcript was shown to correlate exactly with a three-allele HaeIII RFLP. Both polymorphisms apparently result from a variation in the number of ubiquitin coding units per UbC allele. Transcriptionally active alleles containing seven, eight, or nine coding units were observed, at frequencies suggesting that alleles of higher coding-unit number are selectively retained in the population. We propose unequal crossover events, promoted by the highly repetitive structure of the polyubiquitin gene, as a basis for the coding-unit number variation, and we present preliminary evidence for such a crossover, on the basis of analysis of known UbC DNA sequences.