Researchers have assembled the genomes of an orang-utan and a chimpanzee without incorporating any human DNA for the first time, allowing for a more accurate evaluation of their genotypes. Previous ape genome assemblies have relied on using human genetic material to fill in any gaps, and this has meant that we haven’t been able to draw firm conclusions from the data. In particular, this approach may have skewed efforts to ascertain how similar we really are to our closest living relatives. The research was published in Science last week.

Previous attempts at assembling the genomes of great apes have been hindered by difficulties in resolving certain genetic regions. To counter this, researchers have typically ‘plugged the gaps’ using fragments of human DNA to build a complete genome. While this approach has allowed us to examine full genomes, it has meant that we cannot reliably study the differences between our species and theirs and this has impacted our ability to investigate our own evolution.

Now, new research led by a multi-institutional team has successfully assembled the genomes of an orang-utan and a chimpanzee without using any human DNA at all. To do so, the team used long-read Single-Molecule Real-Time (SMRT) sequencing to read more than 500,000 full-length complementary DNA samples from induced pluripotent stem cells, which were then assembled using de novo techniques.

The study also used the newly constructed genomes to draw conclusions about the variations between humans and apes. For example, the team were able to identify 17,789 variants in human genomes that have been linked to gene regulation and which did not appear to be present in the ape genotypes, suggesting that the variants emerged after our evolutionary divergence. Once identified, these genes were investigated for their functions.

“Of the 17,789 fixed human-specific insertions and deletions, we focus on those of potential functional effect,” the paper reads. “We identify 90 that are predicted to disrupt genes and an additional 643 that likely affect regulatory regions, more than doubling the number of human-specific deletions that remove regulatory sequence in the human lineage.”

The researchers also investigated beyond the genotypes by examining chimp brain organoids, enabling them to study how brain development might vary between humans and chimpanzees.

This work is still in the preliminary stages and only involved one complete genome for each type of great ape involved. As a result, there is a limit to the conclusions that can be drawn from this work.

“Despite this more comprehensive assessment of structural variation, not all SV types have been fully resolved among the great apes,” the authors wrote. “In particular, we are still missing many larger, more complex events, including inversions and SDs that have differentially evolved between the lineages.”

However, despite these limitations, this work is indicative of what we may be able to learn about our closest living relatives using new genomic technologies.

“Our goal is to generate multiple ape genomes with as high quality as the human genome,” said Evan Eichler, PhD, co-lead scientist in the study. “Only then will we be able to truly understand the genetic differences that make us uniquely human.”