Genes with human-specific features are primarily involved with brain, immune and metabolic evolution.

BACKGROUND: Humans have adapted to widespread changes during the past 2 million years in both environmental and lifestyle factors. This is evident in overall body alterations such as average height and brain size. Although we can appreciate the uniqueness of our species in many aspects, molecular variations that drive such changes are far from being fully known and explained. Comparative genomics is able to determine variations in genomic sequence that may provide functional information to better understand species-specific adaptations. A large number of human-specific genomic variations have been reported but no currently available dataset comprises all of these, a problem which contributes to hinder progress in the field. RESULTS: Here we critically update high confidence human-specific genomic variants that mostly associate with protein-coding regions and find 856 related genes. Events that create such human-specificity are mainly gene duplications, the emergence of novel gene regions and sequence and structural alterations. Functional analysis of these human-specific genes identifies adaptations to brain, immune and metabolic systems to be highly involved. We further show that many of these genes may be functionally associated with neural activity and generating the expanded human cortex in dynamic spatial and temporal contexts. CONCLUSIONS: This comprehensive study contributes to the current knowledge by considerably updating the number of human-specific genes following a critical bibliographic survey. Human-specific genes were functionally assessed for the first time to such extent, thus providing unique information. Our results are consistent with environmental changes, such as immune challenges and alterations in diet, as well as neural sophistication, as significant contributors to recent human evolution.

Using Human iPSC-Derived Neurons to Uncover Activity-Dependent Non-Coding RNAs.

Humans are arguably the most complex organisms present on Earth with their ability to imagine, create, and problem solve. As underlying mechanisms enabling these capacities reside in the brain, it is not surprising that the brain has undergone an extraordinary increase in size and complexity within the last few million years. Human induced pluripotent stem cells (hiPSCs) can be differentiated into many cell types that were virtually inaccessible historically, such as neurons. Here, we used hiPSC-derived neurons to investigate the cellular response to activation at the transcript level. Neuronal activation was performed with potassium chloride (KCl) and its effects were assessed by RNA sequencing. Our results revealed the involvement of long non-coding RNAs and human-specific genetic variants in response to neuronal activation and help validate hiPSCs as a valuable resource for the study of human neuronal networks. In summary, we find that genes affected by KCl-triggered activation are implicated in pathways that drive cell proliferation, differentiation, and the emergence of specialized morphological features. Interestingly, non-coding RNAs of various classes are amongst the most highly expressed genes in activated hiPSC-derived neurons, thus suggesting these play crucial roles in neural pathways and may significantly contribute to the unique functioning of the human brain.