Genes involved in XLMR are more constrained in their evolution between human and macaque as measured by the dN/dS ratio (nonsynonymous changes per nonsynonymous site/synonymous changes per synonymous site) of 0.17 than genes associated with a disease other than mental retardation (0.31, P = 0.009) or genes not associated with a genetic disease (0.32, P = 0.003). Similarly, their amino acid compositions are more highly conserved between human and mouse compared to the other two classes (P < 0.01 for both comparisons). Previous studies have reported that genes implicated in nervous system diseases, genes associated with neurological functions and genes expressed in the brain undergo more purifying selection than genes in other functional classes28-30. The source of this evolutionary constraint is unclear.
