Reintroduction of the archaic variant of NOVA1 into cortical organoids impairs neurodevelopment

Reintroduction of the archaic variant of NOVA1 into cortical organoids impairs neurodevelopment

Brain organoids with Neanderthal genes

The genomes of Neanderthals and modern humans are broadly very similar. To understand the impact of genetic variants specific to modern humans, Trujillo et al. performed genome-wide analysis to identify 61 coding variants in genes encoding proteins. Identifying the gene encoding the RNA binding protein NOVA1 as a primary candidate for functional analyzes, they introduced the archaic gene variant into human pluripotent stem cells and generated brain organoids. These organoids have shown alterations in gene expression and splicing, as well as in morphology and synaptogenesis, suggesting that this method could be used to explore other genetic changes that underlie the phenotypic traits separating our species. of his missing parents.

Science, this issue p. eaax2537

Structured summary

INTRODUCTION

Current views of human evolution, as supported by the fossil record, indicate that many branches of the hominid lineage have appeared, but only one has survived so far. The Neanderthals and Denisovans, two of these extinct lineages, are our closest evolutionary relatives and therefore provide the most subtle genetic and phenotypic contrast of our species. Comparison of …

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