scholarly journals Evolution and cell-type specificity of human-specific genes preferentially expressed in progenitors of fetal neocortex

2017 ◽  
Author(s):  
Marta Florio ◽  
Michael Heide ◽  
Holger Brandl ◽  
Anneline Pinson ◽  
Sylke Winkler ◽  
...  
Keyword(s):  
Human Evolution ◽  
Neural Progenitor Cell ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Protein Coding ◽  
Neocortical Development ◽  
Human Genes ◽  
Stem And Progenitor Cells ◽  
Developing Neocortex ◽  
Human Specific

AbstractTo understand the molecular basis underlying the expansion of the neocortex during primate, and notably human, evolution, it is essential to identify the genes that are particularly active in the neural stem and progenitor cells of developing neocortex. Here, we have used existing transcriptome datasets to carry out a comprehensive screen for protein-coding genes preferentially expressed in progenitors of fetal human neocortex. In addition to the previously studied gene ARHGAP11B, we show that ten known and two newly identified human-specific genes exhibit such expression, however with distinct neural progenitor cell-type specificity compared to their ancestral paralogs. Furthermore, we identify 41 additional human genes with progenitor-enriched expression which have orthologs only in primates. Our study not only provides a resource of genes that are candidates to exert specific, and novel, roles in neocortical development, but also reveals that distinct mechanisms gave rise to these genes during primate, and notably human, evolution.

scholarly journals Evolution and cell-type specificity of human-specific genes preferentially expressed in progenitors of fetal neocortex

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Marta Florio ◽  
Michael Heide ◽  
Anneline Pinson ◽  
Holger Brandl ◽  
Mareike Albert ◽  
...  
Keyword(s):  
Human Evolution ◽  
Expression Profiles ◽  
Neural Progenitor Cell ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Protein Coding ◽  
Functional Studies ◽  
Basal Progenitor ◽  
Stem And Progenitor Cells ◽  
Human Specific

Understanding the molecular basis that underlies the expansion of the neocortex during primate, and notably human, evolution requires the identification of genes that are particularly active in the neural stem and progenitor cells of the developing neocortex. Here, we have used existing transcriptome datasets to carry out a comprehensive screen for protein-coding genes preferentially expressed in progenitors of fetal human neocortex. We show that 15 human-specific genes exhibit such expression, and many of them evolved distinct neural progenitor cell-type expression profiles and levels compared to their ancestral paralogs. Functional studies on one such gene, NOTCH2NL, demonstrate its ability to promote basal progenitor proliferation in mice. An additional 35 human genes with progenitor-enriched expression are shown to have orthologs only in primates. Our study provides a resource of genes that are promising candidates to exert specific, and novel, roles in neocortical development during primate, and notably human, evolution.

scholarly journals Endogenous Retroviruses and Human Evolution

2002 ◽  
Vol 3 (6) ◽  
pp. 494-498 ◽  
Author(s):  
Konstantin Khodosevich ◽  
Yuri Lebedev ◽  
Eugene Sverdlov
Keyword(s):  
Human Genome ◽  
Human Evolution ◽  
Endogenous Retroviruses ◽  
Regulatory Sequences ◽  
Coding Regions ◽  
Regulatory Systems ◽  
Human Genes ◽  
Functional Consequences ◽  
Polyadenylation Signals ◽  
Human Specific

Humans share about 99% of their genomic DNA with chimpanzees and bonobos; thus, the differences between these species are unlikely to be in gene content but could be caused by inherited changes in regulatory systems. Endogenous retroviruses (ERVs) comprise ∼ 5% of the human genome. The LTRs of ERVs contain many regulatory sequences, such as promoters, enhancers, polyadenylation signals and factor-binding sites. Thus, they can influence the expression of nearby human genes. All known human-specific LTRs belong to the HERV-K (human ERV) family, the most active family in the human genome. It is likely that some of these ERVs could have integrated into regulatory regions of the human genome, and therefore could have had an impact on the expression of adjacent genes, which have consequently contributed to human evolution. This review discusses possible functional consequences of ERV integration in active coding regions.

scholarly journals Human-specific ARHGAP11B induces hallmarks of neocortical expansion in developing ferret neocortex

2018 ◽  
Author(s):  
Nereo Kalebic ◽  
Carlotta Gilardi ◽  
Mareike Albert ◽  
Takashi Namba ◽  
Katherine R. Long ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Progenitor Cell ◽  
Radial Glia ◽  
Specific Gene ◽  
Cell Type ◽  
Embryonic Mouse ◽  
Neuron Density ◽  
Developing Neocortex ◽  
Radial Dimension ◽  
Human Specific

AbstractThe evolutionary increase in size and complexity of the primate neocortex is thought to underlie the higher cognitive abilities of humans. ARHGAP11B is a human-specific gene that, based on its expression pattern in fetal human neocortex and progenitor effects in embryonic mouse neocortex, has been proposed to have a key function in the evolutionary expansion of the neocortex. Here, we study the effects of ARHGAP11B expression in the developing neocortex of the gyrencephalic ferret. In contrast to its effects in mouse, ARHGAP11B markedly increases proliferative basal radial glia, a progenitor cell type thought to be instrumental for neocortical expansion, and results in extension of the neurogenic period and an increase in upper-layer neurons. As a consequence, the postnatal ferret neocortex exhibits an increased neuron density in the upper cortical layers and expands in the radial dimension. Thus, human-specific ARHGAP11B can elicit hallmarks of neocortical expansion in developing ferret neocortex.

scholarly journals Author response: Evolution and cell-type specificity of human-specific genes preferentially expressed in progenitors of fetal neocortex

2018 ◽  
Author(s):  
Marta Florio ◽  
Michael Heide ◽  
Anneline Pinson ◽  
Holger Brandl ◽  
Mareike Albert ◽  
...  
Keyword(s):  
Author Response ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Human Specific

scholarly journals Human-specific ARHGAP11B induces hallmarks of neocortical expansion in developing ferret neocortex

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Nereo Kalebic ◽  
Carlotta Gilardi ◽  
Mareike Albert ◽  
Takashi Namba ◽  
Katherine R Long ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Progenitor Cell ◽  
Radial Glia ◽  
Specific Gene ◽  
Cell Type ◽  
Cortical Layers ◽  
Embryonic Mouse ◽  
Neuron Density ◽  
Developing Neocortex ◽  
Human Specific

The evolutionary increase in size and complexity of the primate neocortex is thought to underlie the higher cognitive abilities of humans. ARHGAP11B is a human-specific gene that, based on its expression pattern in fetal human neocortex and progenitor effects in embryonic mouse neocortex, has been proposed to have a key function in the evolutionary expansion of the neocortex. Here, we study the effects of ARHGAP11B expression in the developing neocortex of the gyrencephalic ferret. In contrast to its effects in mouse, ARHGAP11B markedly increases proliferative basal radial glia, a progenitor cell type thought to be instrumental for neocortical expansion, and results in extension of the neurogenic period and an increase in upper-layer neurons. Consequently, the postnatal ferret neocortex exhibits increased neuron density in the upper cortical layers and expands in both the radial and tangential dimensions. Thus, human-specific ARHGAP11B can elicit hallmarks of neocortical expansion in the developing ferret neocortex.

scholarly journals Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhongbo Chen ◽  
◽  
David Zhang ◽  
Regina H. Reynolds ◽  
Emil K. Gustavsson ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Purifying Selection ◽  
Whole Genome Sequencing Data ◽  
Human Lineage ◽  
Sequencing Data ◽  
Protein Coding ◽  
Potential Association ◽  
High Depth ◽  
Specific Sequences ◽  
Human Specific

AbstractKnowledge of genomic features specific to the human lineage may provide insights into brain-related diseases. We leverage high-depth whole genome sequencing data to generate a combined annotation identifying regions simultaneously depleted for genetic variation (constrained regions) and poorly conserved across primates. We propose that these constrained, non-conserved regions (CNCRs) have been subject to human-specific purifying selection and are enriched for brain-specific elements. We find that CNCRs are depleted from protein-coding genes but enriched within lncRNAs. We demonstrate that per-SNP heritability of a range of brain-relevant phenotypes are enriched within CNCRs. We find that genes implicated in neurological diseases have high CNCR density, including APOE, highlighting an unannotated intron-3 retention event. Using human brain RNA-sequencing data, we show the intron-3-retaining transcript to be more abundant in Alzheimer’s disease with more severe tau and amyloid pathological burden. Thus, we demonstrate potential association of human-lineage-specific sequences in brain development and neurological disease.

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