Mutation patterns of amino acid tandem repeats in the human proteome

We identified 137 polymorphic variants in 115 different amino acid tandem repeats. Of these, 77 contained amino acid substitutions and 60 contained gaps (expansions or contractions of the repeat unit). The analysis showed that at least about 21% of the repeats might be polymorphic in humans. We compared the mutations found in different types of amino acid repeats and in adjacent regions. Overall, repeats showed a five-fold increase in the number of gap mutations compared to adjacent regions, reflecting the action of slippage within the repetitive structures. Gap and substitution mutations were very differently distributed between different amino acid repeat types. Among repeats containing gap variants we identified several disease and candidate disease genes.This is the first report at a genome-wide scale of the types of mutations occurring in the amino acid repeat component of the human proteome. We show that the mutational dynamics of different amino acid repeat types are very diverse. We provide a list of loci with highly variable repeat structures, some of which may be potentially involved in disease.Single amino acid tandem repeats, also called homopolymeric amino acid tracts, are very abundant in eukaryotic proteins and are present in nearly one-fifth of human gene products [1,2]. They can be encoded by runs of a single codon or by a mixture of synonymous codons. Pure runs of the same codon will be susceptible to expansions and contractions of the core repetitive unit via slippage of trinucleotide repeat units [3,4]. In accordance, repeats that are poorly conserved in orthologous genes across different species are more often encoded by homogeneous codon tracts than repeats that are well conserved across species [2,5].It has been proposed that the high mutability associated with slippage may provide an evolutionary advantage in the adaptation to new environments and to the rapid evolution of morphological traits [6,7]. But slippage can also have pathogenic effe