High-resolution comparative analysis of the Great Ape genomes: structural variation and brain-expressin differences

In these GEITP pages, we have often chatted about primate evolution –– because evolution is a representation of the genes, in genomes of each species, interacting/responding to the environment, over extended time periods (hundreds, thousands; hundreds of thousands of years). Evolutionary scientists have long been interested in the functional genetic differences that distinguish humans from other ape species. Human and chimpanzee protein-encoding changes and structural differences in regulatory DNAs, or in the copy numbers within gene families, have all been involved in adaptation of the human-ape ancestor to the changing environment into which hominin species began developing. For example, several potentially high-impact regulatory changes and human-specific genes that are important in (brain nerve) synapse density, neuronal cell count, and other morphological differences in the brain, are all well known. Most of these genetic differences, however, were not initially recognized during early comparisons of human and ape genomes, because these genetic changes mapped to regions of rapid genomic structural change that had not yet been resolved in draft genome assemblies.

Authors [see attached article] combined “long-read” sequence assembly and full-length complementary DNA (cDNA; this is DNA that has been reverse-transcribed from messenger RNA of coding genes) sequencing with a multi-platform scaffolding approach, in order to start from the beginning in producing unequivocal chimpanzee and orangutan genome assemblies. By comparing these two ape genome assemblies with two long-read de novo human genome assemblies and a gorilla genome assembly –– authors characterized lineage-specific, versus shared, great ape genetic variation, which ranged from single–base pair variants to mega–base pair (Mbp)–sized variants (“mega-base” = 1 million bases).

Authors identified ~17,000 fixed human-specific structural gene variants which helped identify genic and putative regulatory changes that have emerged in humans –– since humans’ divergence from non-human apes. Intringuingly, these DNA variants were found to be enriched near genes that are down-regulated in human, compared to those in chimpanzee cerebral organoids, particularly in cells analogous to radial glial neural progenitors (such precursors of glial cells in the brain include oligodendrocytes, astrocytes, ependymal cells, Schwann cells, microglia, and satellite cells).


Science 8 June 2o18; 360: 1085 + whole article

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