https://doi.org/10.1002/ajpa.24504 The genetic basis of human uniqueness remains one of the most enduring mysteries in biological anthropology. The goal of this research project was to identify, characterize, and infer the origin and function of novel elements in the human genome that are not functionally shared with other apes. Our approach toward this goal was to utilize a variety of genome alignment tools to discover islands of non-conserved DNA sequences, followed by theoretical and computational analysis of those regions using synteny sequence analysis. We discovered families of microRNA genes on human chromosome 21 with no detectable orthologs in the other African apes.