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Atypical mutational properties of human chromosome 21 suggested by comparative genome-scale analyses

Mutation of genetic material is a necessary component of evolutionary change. There is evidence for both intragenome and intergenome heterogeneity in terms of mutation frequencies. Reported comparisons of DNA sequence differences between human and chimpanzee (Pan troglodytes) suggest that human chromosome 21 may exhibit mutational hypervariability relative to the other autosomes. In the present study, further evidence is provided for such hypervariability based on large-scale analyses of amino acid composition of (translated) human genes and pseudogenes. A comparison of the variation in the above cases (i.e., DNA sequence differences and amino acid composition differences) yields similar ratios (1.2–1.4) for chromosome 21 relative to the other autosomes, e.g., human chromosome 22 – an autosome that is more typical in this respect and is of similar size to 21. Human chromosome 21 is also presented in this study as being atypical in terms of reported associations between mutation rates and GC content or CpG dinucleotides. In terms of GC distribution patterns, a comparison of NT_011512 and NT_011520 contigs revealed a lower heterogeneity for human chromosome 21 relative to 22. Possible hypermutability of chromosome 21 is further discussed in the context of GC patterns, reported long interspersed nuclear element content (LINE1s), and the implications of these parameters for chromatin structure.