Reduced purine biosynthesis in humans after their divergence from Neandertals

We analyze the metabolomes of humans, chimpanzees, and macaques in muscle, kidney and three different regions of the brain. Although several compounds in amino acid metabolism occur at either higher or lower concentrations in humans than in the other primates, metabolites downstream of adenylosuccinate lyase, which catalyzes two reactions in purine synthesis, occur at lower concentrations in humans. This enzyme carries an amino acid substitution that is present in all humans today but absent in Neandertals. By introducing the modern human substitution into the genomes of mice, as well as the ancestral, Neandertal-like substitution into the genomes of human cells, we show that this amino acid substitution contributes to much or all of the reduction of de novo synthesis of purines in humans

Comparative genomics and evolution of transcriptional regulons in Proteobacteria

Comparative genomics approaches are broadly used for analysis of transcriptional regulation in bacterial genomes. In this work, we identified binding sites and reconstructed regulons for 33 orthologous groups of transcription factors (TFs) in 196 reference genomes from 21 taxonomic groups of Proteobacteria. Overall, we predict over 10,600 TF binding sites and identified more than 15,600 target genes for 1,896 TFs constituting the studied orthologous groups of regulators. These include a set of orthologs for 21 metabolism-associated TFs from Escherichia coli and/or Shewanella that are conserved in five or more taxonomic groups and several additional TFs that represent non-orthologous substitutions of the metabolic regulators in some lineages of Proteobacteria. By comparing gene contents of the reconstructed regulons, we identified the core, taxonomy-specific and genome-specific TF regulon members and classified them by their metabolic functions. The detailed analysis of ArgR, TyrR, TrpR, HutC, HypR and other amino acid-specific regulons demonstrated remarkable differences in regulatory strategies used by various lineages of Proteobacteria. The obtained genomic collection of in silico reconstructed TF regulons contains a large number of new regulatory interactions that awaits future experimental validation. It provides a framework for future evolutionary studies of transcriptional regulatory networks in Bacteria. It can be also used for functional annotation of putative metabolic transporters and enzymes that are abundant in the reconstructed regulons

Comparative genomics and evolution of transcriptional regulons in Proteobacteria.

Comparative genomics approaches are broadly used for analysis of transcriptional regulation in bacterial genomes. In this work, we identified binding sites and reconstructed regulons for 33 orthologous groups of transcription factors (TFs) in 196 reference genomes from 21 taxonomic groups of Proteobacteria. Overall, we predict over 10 600 TF binding sites and identified more than 15 600 target genes for 1896 TFs constituting the studied orthologous groups of regulators. These include a set of orthologues for 21 metabolism-associated TFs from Escherichia coli and/or Shewanella that are conserved in five or more taxonomic groups and several additional TFs that represent non-orthologous substitutions of the metabolic regulators in some lineages of Proteobacteria. By comparing gene contents of the reconstructed regulons, we identified the core, taxonomy-specific and genome-specific TF regulon members and classified them by their metabolic functions. Detailed analysis of ArgR, TyrR, TrpR, HutC, HypR and other amino-acid-specific regulons demonstrated remarkable differences in regulatory strategies used by various lineages of Proteobacteria. The obtained genomic collection of in silico reconstructed TF regulons contains a large number of new regulatory interactions that await future experimental validation. The collection provides a framework for future evolutionary studies of transcriptional regulatory networks in Bacteria. It can be also used for functional annotation of putative metabolic transporters and enzymes that are abundant in the reconstructed regulons

Human-specific features of spatial gene expression and regulation in eight brain regions

ヒトとチンパンジーの脳の違いを発見 --霊長類脳の遺伝子発現変動とエピジェネティック変動の網羅的解析--. 京都大学プレスリリース. 2018-08-03.Molecular maps of the human brain alone do not inform us of the features unique to humans. Yet, the identification of these features is important for understanding both the evolution and nature of human cognition. Here, we approached this question by analyzing gene expression and H3K27ac chromatin modification data collected in eight brain regions of humans, chimpanzees, gorillas, a gibbon, and macaques. An analysis of spatial transcriptome trajectories across eight brain regions in four primate species revealed 1851 genes showing human-specific transcriptome differences in one or multiple brain regions, in contrast to 240 chimpanzee-specific differences. More than half of these human-specific differences represented elevated expression of genes enriched in neuronal and astrocytic markers in the human hippocampus, whereas the rest were enriched in microglial markers and displayed human-specific expression in several frontal cortical regions and the cerebellum. An analysis of the predicted regulatory interactions driving these differences revealed the role of transcription factors in species-specific transcriptome changes, and epigenetic modifications were linked to spatial expression differences conserved across species