We also generated and analyzed an African genome and an effectively haploid human genome complement to distinguish fixed differences in the human ancestral lineage and to further mitigate human genome reference biases. Using long-read, long-range sequence and mapping technologies ( 13– 15), we generated new great ape genome assemblies along with full-length cDNA annotation without guidance from the human genome. This bias has effectively “humanized” other ape genome assemblies, minimizing potential structural and transcript differences observed between the species. Second, the higher quality human genome assemblies have often been used to guide the final stages of nonhuman genome projects, including the order and orientation of sequence contigs and, perhaps more importantly, the annotation of genes. Therefore, a large fraction of human-specific insertions and deletions, including those that alter regulatory sequences, are not resolved. The presence of tens to hundreds of thousands of gaps in ape genomes limits the proportion of the genome that can be compared in a multi-species sequence alignment. First, there is considerable heterogeneity in the contiguity of ape genome assemblies. Most of these genetic differences, however, were not initially recognized upon comparison of human and ape genomes because the genetic changes mapped to regions of rapid genomic structural change that were not resolved in draft genome assemblies.ĭespite recent efforts to sequence and assemble ape genomes ( 10– 12), our understanding of structural differences, and particularly those specific to the human lineage, remains far from complete. Indeed, several potentially high-impact regulatory changes ( 4, 5) and human-specific genes ( 6– 9) that are important in synapse density, neuronal count, and other morphological differences have been identified. Human and chimpanzee protein-encoding changes and structural differences in regulatory DNA or in the copy number of gene families have all been implicated in adaptation ( 2, 3). Scientists have long been interested in the functional genetic differences that distinguish humans from other ape species ( 1). deposited sequencing data and performed NCBI/UCSC annotation. provided iPSC material M.D., I.T.F., V.A.S. provided human genome assembly sequence data J.S. annotated genome assembly and assessed gene models and accuracy. generated Bionano Genomics de novo assembled optical maps, hybrid scaffolding with sequence assemblies, structural variation detection, and cross-platform data comparison I.T.F., J.A., M.D., B.P. constructed the AGP A.R.H., A.W.C.P., J.L., E.T.L. performed bioinformatics analyses S.M., M.V., A.R.H., Z.N.K. prepared libraries and generated sequencing data D.G., B.J.N., M.J.P.C., C.M.H., Z.N.K., M.L.D., S.M., E.R.H., O.S.M., P.H. designed and planned experiments K.M.M., J.G.U., R.Q., A.E.W., M.S., K.H., C.B., R.S.F.