Transposable Elements and DNA Methylation Create in Embryonic Stem Cells Human-Specific Regulatory Sequences Associated with Distal Enhancers and Noncoding RNAs.
Bottom Line: Despite significant progress in the structural and functional characterization of the human genome, understanding of the mechanisms underlying the genetic basis of human phenotypic uniqueness remains limited.Preliminary estimates suggest that emergence of one novel NANOG-binding site detectable in hESC required 466 years of evolution.A proximity placement model is proposed explaining how a 33-47% excess of NANOG, CTCF, and POU5F1 proteins immobilized on a DNA scaffold may play a functional role at distal regulatory elements.
Affiliation: Institute of Engineering in Medicine, University of California, San Diego The Stanford University School of Medicine, Department of Surgery, Stanford, California firstname.lastname@example.org email@example.com.Show MeSH
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Mentions: An elite set of 24 genes regulating brain size and behavior in humans has been identified, which also shows markedly accelerated rates of protein evolution within the lineage leading from ancestral primates to humans (Dorus et al. 2004). This set of genes may play an important role in defining the phenotypic uniqueness of Homo sapiens by contributing to a dramatic increase in the size and complexity of the human brain during evolution (Dorus et al. 2004). Thus, it was interesting to determine how candidate human-specific TF-binding sites are positioned in the genome relative to the genomic coordinates of these 24 genes. For this analysis, the housekeeping genes were considered as the appropriate control gene set because they perform the essential basic cellular functions conserved across different species and are thus likely to evolve under evolutionary constraints without any significant impact of positive selection. Consistent with these assumptions and in contrast to the nervous system-related genes, housekeeping genes have statistically indistinguishable evolutionary rates in primates and rodents (Dorus et al. 2004). Because the set of 24 genes is characterized by a high evolutionary rate and manifests marked evolutionary rate disparities between primates and rodents (Dorus et al. 2004), the stringency of the comparison was further increased by selecting a set of 53 housekeeping genes with the highest rates of evolution in primates (fig. 4 and supplementary fig. S6, Supplementary Material online).Fig. 4.—
Affiliation: Institute of Engineering in Medicine, University of California, San Diego The Stanford University School of Medicine, Department of Surgery, Stanford, California firstname.lastname@example.org email@example.com.