Abstract
Comparisons of the genomes of Neandertals and Denisovans with present-day human genomes have suggested that the gene RUNX2, which encodes a transcription factor, may have been positively selected during early human evolution. Here, we overexpress RUNX2 in ten human cell lines and identify genes that are directly or indirectly affected by RUNX2 expression. We find a number of genes not previously known to be affected by RUNX2 expression, in particular BIRC3, genes encoded on the mitochondrial genome, and several genes involved in bone and tooth formation. These genes are likely to provide inroads into pathways affected by RUNX2 and potentially by the evolutionary changes that affected RUNX2 in modern humans.
Highlights
Genome sequences of the closest extinct evolutionary relatives of present-day humans, Neandertals [1] and Denisovans [2,3], allow genomic changes that occurred recently during human evolution to be identified
As a result long genomic regions where all present-day human genomes are more closely related to each other than to the archaic genomes will tend to have been affected by positive selection in modern humans after their separation from an ancestor shared with Neandertals and Denisovans
This vector was used in transfections of ten cell lines: the osteoblastoma, hFOB1.19; the osteosarcomas, Saos-2, U-2 Os; the neuroblastomas, SH-SY5Y, SK-N-SH, IMR-32; the astrocytoma, U-87 MG; the adenocarcinoma, ACHN; the hepatoma, HepG2; and the cervical carcinoma, HeLa-S3
Summary
Genome sequences of the closest extinct evolutionary relatives of present-day humans, Neandertals [1] and Denisovans [2,3], allow genomic changes that occurred recently during human evolution to be identified. They allow putative selective sweeps that occurred early during modern human evolution to be detected. This is because Neandertals and Denisovans are so closely related to presentday humans that a majority of their genomes falls into the variation of present-day humans. In another screen for positive selection that occurred early during the evolution of modern humans, which is based on the observation of unusually long stretches of high-frequency derived variants shared among distantly related extant human populations, the largest region identified (~ 900kb) contained RUNX2 [4]
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