The role of new genes formed by segmental duplications in human brain development

The Neocortex has undergone a dramatic expansion during primate evolution. In our lab, we aim to characterize gene-regulatory networks that drive the earliest stages of cortical development with a special focus on aspects unique to humans. In work that was recently published in 'Cell'  after many years of exciting discoveries, we revealed the existence of a cluster of human-specific NOTCH2NL genes,  which are highly expressed in neuronal stem cells in the human brain. These human-specific genes were formed by segmental duplications, and their function in neuronal progenitor cells suggest these genes may have contributed to the evolutionary expansion of the human neocortex (https://www.ncbi.nlm.nih.gov/pubmed/29856954).

This gene-family is not alone. Many other multi-copy genes exist in our genome, some of which we know are highly expressed during early developmental stages of human cerebral organoid development. Since very recent gene-duplications result in two nearly identical and therefore nearly indistinguishable paralogous genes on the genome, most of these duplicated genes have escaped the attention.  

Primate genome evolution: What can differences in the genomes of closely related primate species tell us about the evolution of the human brain.

It is becoming increasingly clear that big chromosomal rearrangements such as gene duplications may have had a significant impact on the evolution of species. Current research in my group focusses on neurally expressed multi-copy genes and the impact of gene duplication events on the evolution of human neural gene-regulatory pathways.

Generation of human brain tissue in a dish