Improved ape genome assemblies give human evolution insights

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New, higher-quality assemblies of great ape genomes have now been generated without the guidance of the human reference genome. The effort to reduce “humanizing” discovery bias in great ape genomes provides a clearer view of the genetic differences that arose as humans diverged from other primates.
In the June 8 issue of Science, researchers report on improved orangutan and chimpanzee genomes that were built from scratch using long-read PacBio sequencing and long-range mapping technology. The highly contiguous, newly assembled genomes present a better resource for novel gene discovery and high-resolution comparative genomics amongst the great apes.
The multi-institutional project, involving more than 40 scientists at a dozen research centers, was led by Zev N. Kronenberg and Evan Eichler, a Howard Hughes Medical Institute investigator in the Department of Genome Sciences at the University of Washington School of Medicine. Kronenberg is now a senior computational biologist at Phase Genomics.
The scientists note that many of the genetic differences between humans and other apes were not recognized when their genomes were first compared. Areas of rapid structural change were still nebulous in those early draft genome assemblies. This made them difficult to compare and limited the discovery of the functional differences that distinguish humans from other apes.
By coupling long-read sequence assembly with a hybrid genome scaffolding approach, the researchers resolved the majority of gaps in the ape genomes. Some of these gaps contained genes, which are now correctly annotated in the new genomes. To better understand the gene structures, the authors complemented this effort by sequencing more than 500,000 full-length genes from each species.
The newest investigation provides the most comprehensive catalog of genetic variants that were gained or lost on different ape lineages. Some of these variants affect how genes are differentially expressed among humans and apes.
The researchers examined the possible influence of some of the genetic variants and gene function regulators on such areas as human and ape dietary differences, anatomy, and brain formation.
The research team’s comparative analysis of human and great ape genomes also included a gorilla assembly, a new assembly of an African human genome, and a human haploid hydatidform mole assembly. (Because they contain only half of the paired human chromosomes, studies of these rare human growths help tell similar duplicated genes apart.) All the genomes were sequenced and assembled using the same process.
Additionally, the researchers studied brain organoids – laboratory-grown tissues coaxed from stem cells of apes or humans and forming a simplified version of organ parts. These brain proxies were examined to try to understand how differences in gene expression during brain development in humans and chimps might account for chimps’ smaller brain volume, which is three times less than human brain volume. There are also significant dissimilarities in cortical structures in human and chimp brains.
Read the full article on UW Medicine here.

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