Expression of human‐specific ARHGAP11B in mice leads to neocortex expansion and increased memory flexibility

Abstract Objectives Human identification systems based on STRs are widely used in human population genetics and forensic analysis. This study aimed to validate the cross-reactivity of three widely known human-specific STR identification systems i.e. GlobalFiler™ PCR Amplification Kit, Investigator 24plex QS Kit, and PowerPlex® Fusion 6C in chimpanzee. Results The present study revealed the successful amplification of 18 loci using GlobalFiler™ PCR Amplification Kit, 18 loci using Investigator 24plex QS Kit, and 20 loci using PowerPlex® Fusion 6C system. The marker Amelogenin (AMEL) showed differential allele size between male and female revealing the gender identity of chimpanzees and thus validates their application concerning forensic examination, population estimation, and genetic analysis.

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Evidence for opposing selective forces operating on human-specific duplicated TCAF genes in Neanderthals and humans

Nature Communications ◽

10.1038/s41467-021-25435-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

PingHsun Hsieh ◽

Vy Dang ◽

Mitchell R. Vollger ◽

Yafei Mao ◽

Tzu-Hsueh Huang ◽

...

Keyword(s):

Copy Number ◽

Homo Sapiens ◽

Segmental Duplications ◽

Sensor Protein ◽

Long Read ◽

Number Variation ◽

Selective Forces ◽

Structural Mutations ◽

Cold Sensor ◽

Human Specific

AbstractTRP channel-associated factor 1/2 (TCAF1/TCAF2) proteins antagonistically regulate the cold-sensor protein TRPM8 in multiple human tissues. Understanding their significance has been complicated given the locus spans a gap-ridden region with complex segmental duplications in GRCh38. Using long-read sequencing, we sequence-resolve the locus, annotate full-length TCAF models in primate genomes, and show substantial human-specific TCAF copy number variation. We identify two human super haplogroups, H4 and H5, and establish that TCAF duplications originated ~1.7 million years ago but diversified only in Homo sapiens by recurrent structural mutations. Conversely, in all archaic-hominin samples the fixation for a specific H4 haplotype without duplication is likely due to positive selection. Here, our results of TCAF copy number expansion, selection signals in hominins, and differential TCAF2 expression between haplogroups and high TCAF2 and TRPM8 expression in liver and prostate in modern-day humans imply TCAF diversification among hominins potentially in response to cold or dietary adaptations.

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

Nature Communications ◽

10.1038/s41467-021-22262-5 ◽

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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