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De Novo Gene Birth and the Evolution of the Human Brain

NOMIS Project 2023

— 2028

What is the nature of mutations underlying phenotypic evolution? In addition to genetic modifications of preexisting genes that can lead to differences in their sequences or activities, the “birth” of new genes with novel functions significantly contributed to the evolution of species-specific traits. The de novo emergence of protein-coding genes—that is, their origination “from scratch” (from previously noncoding DNA sequences)—represents a particularly intriguing mechanism of new gene origination. However, this mechanism was long considered to be highly unlikely, and its prevalence and evolutionary relevance remain poorly understood.

The project De Novo Gene Birth and the Evolution of the Human Brain aims to close this critical gap by systematically tracing and characterizing de novo genes that contributed to the evolution of a key organ that changed in profound ways on the human lineage and defines our species: The brain. Specifically, the investigators seek to unravel the contribution of de novo genes to the evolutionary expansion and elaboration of the neocortex, the seat of higher cognitive functions in humans. The research focuses on the contribution of de novo genes to evolutionary changes of developmental processes—key drivers of phenotypic innovations, given that adult organ anatomies and functions are set up during development.

The De Novo Gene Birth project will generate and analyze translatome data across a unique set of prenatal developmental tissue samples, and experimentally characterize select de novo genes in state-of-the-art in vitro organoid systems, ex vivo fetal tissue cultures and in vivo transgenic mouse models. Ultimately, the researchers hope to illuminate the prevalence and functional roles of de novo genes in primate cortical development and shed light on the molecular evolution underlying the unique biology of our brain.

The project is being led by Henrik Kaessmann at Heidelberg University in Germany.


NOMIS Researcher(s)