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Through the genomic sands of time

For this issue of neuroDEVELOPMENTS, we celebrate the Nobel Prize awarded to Svante Pääbo in December 2022 for his work deciphering the DNA sequence of ancient hominids. To mark the occasion, we highlight two papers that delve into how evolutionarily recent genome variation in primates has implications for how changes in the development of the cortex have led to psychiatric disorders as our lineage emerged.

Svante Pääbo himself is an author on the first paper, which examines the functional consequences of a single coding amino acid change in humans relative to Neanderthals and Denisovans, archaic hominins that preceded the arrival of modern humans (Pinson et al., 2022). The study presents multiple lines of evidence showing that the modern version of this gene has a clear effect on brain cell proliferation through radial glial cells as they form the frontal lobe.

Taking a different approach, another paper from Craig Lowe at Duke University and colleagues compares the genomes of great apes, archaic hominins, and modern humans to find a set of non-coding changes that distinguish us and our closest relatives from chimpanzees (Mangan et al., 2022). This work identifies over 1000 new gene enhancer elements in modern humans that emerged suddenly under positive selective force and carry elevated risk for psychiatric disorders. These studies illustrate how our new knowledge of ancient DNA opens stunning prospects for our understanding of how human brain development and disease are profoundly linked.

-Ron McKay, PhD, Chief Editor
Lieber Institute for Brain Development

-Venkata S. Mattay, MD
Managing Editor

-Michele Solis, PhD
Science Writer

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Editorial Board

Fred ‘Rusty’ Gage, PhD
President, The Salk Institute for Biological Studies

Daniel Geschwind, MD, PhD
Professor, UCLA School of Medicine

Elizabeth Grove, PhD
Professor, University of Chicago

Jürgen Knoblich, PhD
Interim Scientific Director, Institute of Molecular Biotechnology, Austrian Academy of Sciences

Arnold Kriegstein, MD
Professor, UCSF

Pat Levitt, PhD
Professor, Keck School of Medicine of USC

Mu-Ming Poo, PhD
Director, Institute of Neuroscience, Chinese Academy of Sciences

John Rubenstein, MD, PhD
Professor of Psychiatry, UCSF

Nenad Sestan, MD, PhD
Professor, Yale University

Flora Vaccarino, MD
Professor, Yale University

Chris Walsh, MD, PhD
Chief, Division of Genetics & Genomics, Boston Children’s Hospital

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