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The current human reference genome, GRCh38, represents over 20 years of effort to generate a high-quality assembly, which has benefitted societysup1,2/sup. However, it still has many gaps and errors, and does not represent a biological genome as it is a blend of multiple individualssup3,4/sup. Recently, a high-quality telomere-to-telomere reference, CHM13, was generated with the latest long-read technologies, but it was derived from a hydatidiform mole cell line with a nearly homozygous genomesup5/sup. To address these limitations, the Human Pangenome Reference Consortium formed with the goal of creating high-quality, cost-effective, diploid genome assemblies for a pangenome reference that represents human genetic diversitysup6/sup. Here, in our first scientific report, we determined which combination of current genome sequencing and assembly approaches yield the most complete and accurate diploid genome assembly with minimal manual curation. Approaches that used highly accurate long reads and parent-child data with graph-based haplotype phasing during assembly outperformed those that did not. Developing a combination of the top-performing methods, we generated our first high-quality diploid reference assembly, containing only approximately four gaps per chromosome on average, with most chromosomes within ±1% of the length of CHM13. Nearly 48% of protein-coding genes have non-synonymous amino acid changes between haplotypes, and centromeric regions showed the highest diversity. Our findings serve as a foundation for assembling near-complete diploid human genomes at scale for a pangenome reference to capture global genetic variation from single nucleotides to structural rearrangements.

The history of the genus Pan is a topic of enduring interest. Chimpanzees (Pan troglodytes) are often divided into subspecies, but the population structure and genetic history of chimpanzees across Africa remain unclear. Some population genetics studies have led to speculation that, until recently, this species constituted a single population with ongoing gene flow across its range, which resulted in a continuous gradient of allele frequencies. Chimpanzees, designated here as P. t. ellioti, occupy the Gulf of Guinea region that spans southern Nigeria and western Cameroon at the center of the distribution of this species. Remarkably, few studies have included individuals from this region, hindering the examination of chimpanzee population structure across Africa. Here, we analyzed microsatellite genotypes of 94 chimpanzees, including 32 designated as P. t. ellioti. We find that chimpanzees fall into three major populations: (i) Upper Guinea in western Africa (P. t. verus); (ii) the Gulf of Guinea region (P. t. ellioti); and (iii) equatorial Africa (P. t. troglodytes and P. t. schweinfurthii). Importantly, the Gulf of Guinea population is significantly different genetically from the others, sharing a last common ancestor with the populations in Upper Guinea similar to 0.46 million years ago (mya) and equatorial Africa similar to 0.32 mya. Equatorial chimpanzees are subdivided into up to three populations occupying southern Cameroon, central Africa, and eastern Africa, which may have constituted a single population until similar to 0.10-0.11 mya. Finally, occasional hybridization may be occurring between the Gulf of Guinea and southern Cameroon populations