Phylogenetic analysis supports a link between DUF1220 domain number and primate brain expansion

Abstract

The expansion of DUF1220 domain copy number during human evolution is a dramatic example of rapid and repeated domain duplication. However, the phenotypic relevance of DUF1220 dosage is unknown. Although patterns of expression, homology and disease associations suggest a role in cortical development, this hypothesis has not been robustly tested using phylogenetic methods. Here, we estimate DUF1220 domain counts across 12 primate genomes using a nucleotide Hidden Markov Model. We then test a series of hypotheses designed to examine the potential evolutionary significance of DUF1220 copy number expansion. Our results suggest a robust association with brain size, and more specifically neocortex volume. In contradiction to previous hypotheses we find a strong association with postnatal brain development, but not with prenatal brain development. Our results provide further evidence of a conserved association between specific loci and brain size across primates, suggesting human brain evolution occurred through a continuation of existing processes.