Contrasting patterns of coding and flanking region evolution in mammalian keratin associated protein-1 genes

Mammalian genomes contain a number of duplicated genes, and sequence identity between these duplicates can be maintained by purifying selection. However, between-duplicate recombination can also maintain sequence identity between copies, resulting in a pattern known as concerted evolution where within-genome repeats are more similar to each other than to orthologous repeats in related species. Here we investigated the tandemly-repeated keratin-associated protein 1 (KAP1) gene family, KRTAP1, which encodes proteins that are important components of hair and wool in mammals. Comparison of eutherian mammal KRTAP1 gene repeats within and between species shows a strong pattern of concerted evolution. However, in striking contrast to the coding regions of these genes, we find that the flanking regions have a divergent pattern of evolution. This contrast in evolutionary pattern transitions abruptly near the start and stop codons of the KRTAP1 genes. We reveal that this difference in evolutionary patterns is not explained by conventional purifying selection, nor is it likely a consequence of codon adaptation or reverse transcription of KRTAP1-n mRNA. Instead, the evidence suggests that these contrasting patterns result from short-tract gene conversion events that are biased to the KRTAP1 coding region by selection and/or differential sequence divergence. This work demonstrates the power that gene conversion has to finely shape the evolution of repetitive genes, and provides another distinctive pattern of contrasting evolutionary outcomes that results from gene conversion. A greater emphasis on exploring the evolution of multi-gene eukaryotic families will reveal how common different contrasting evolutionary patterns are in gene duplicates.