Scientists have long been interested in the functional genetic differences that distinguish humans from other ape species. Poor quality ape genome assemblies, “humanized” by using the human genome as the scaffold, have stood in the way of finding out what truly makes us human.

Evan Eichler assembled a large team, including several Bionano scientists, to sequence and assemble two human, one chimpanzee, and one orangutan genome using high-coverage long-read sequencing and Bionano genome mapping. They also sequenced more than 500,000 full-length cDNA samples to construct de novo gene models and map transcript diversity in each ape lineage.

The paper gives a fascinating overview of changes that happened in each great ape lineage. For instance, ~17,000 fixed human-specific structural variants were picked up that identify genic and putative regulatory changes that have emerged in humans since divergence from nonhuman apes. Interestingly, these variants are enriched near genes that are down-regulated in human compared to chimpanzee brains.

Bionano mapping identified several larger, subcytogenetic structural differences that were not detected or sequence-resolved in previous genome assemblies. The authors identified 29 human-chimpanzee-orangutan inversions ranging from 100 kbp to 5 Mbp in size, of which 55% have not been previously described. More than 93% of inversions are flanked by large complex segmental-duplication blocks, 38% of which show evidence of other structural and copy-number variation at the boundaries of the inversion. Even long-read sequencing can’t typically span those long segmental duplications, which is why Bionano can detect such large inversions better than any other technology.

This paper is well worth your attention. Grab it on Science