Insights into brain evolution through the genotype-phenotype connection.

It has recently become possible to start exploring how the genotype translates into human brain morphology and behavior by combining detailed genomic and phenotypic data from thousands of present-day people with archaic genomes of extinct humans, and gene expression data. As a starting point into this emerging interdisciplinary domain, we highlight current debates about which aspects of the modern human brain are unique. We review recent developments from (1) comparative primate neuroscience-a fast-growing field offering an invaluable framework for understanding general mechanisms and the evolution of human-specific traits. (2) paleoanthropology-based on evidence from endocranial imprints in fossil skulls, we trace the evolution from the ape-like brain phenotype of early hominins more than 3 million years ago to the unusual globular brain shape of present-day people. (3) Genomics of present-day and extinct humans. The morphological and genetic differences between modern humans and our closest extinct cousins, the Neandertals, offer important clues about the genetic underpinnings of brain morphology and behavior. The functional consequences of these genetic differences can be tested in animal models, and brain organoids.