Unique and divergent features of human brain development

The human experience is shaped by evolutionary adjustments that have endowed the human brain with advanced cognitive, physiological, and morphological adaptations, surpassing those of other anthropoid primates. Although comparative mammalian studies have provided valuable insights into our evolutionary history, identifying genomic variations underpinning uniquely human phenotypic traits remains challenging. Integration of multiomic modalities with noninvasive brain imaging allows evolutionary hypotheses to be tested in previously intractable ways. This convergence marks a new era, integral to deepening our understanding of what novel and conserved features steer human brain development. In this review, we highlight multimodal efforts to study human brain evolution. We argue that efforts to connect primate and human genotype-to-phenotype relationships will accelerate over the coming years but require careful interpretation when evaluating claims of human uniqueness. Finally, we underscore the importance of continued identification of conserved aspects of brain development and the use of rigorous study designs when evaluating proposed ‘human-specific’ features. • Genetic, molecular, and functional mechanistic interplay to directs brain evolution. • Human neural cell types display transient and evolutionarily divergent features. • Subplate is a transient structure critical for cortical development and evolution. • Regulatory changes direct some human-specific molecular and functional adaptations. • Examination of human uniqueness requires careful comparison with other apes.