Keeping the balance: Trade-offs between human brain evolution, autism, and schizophrenia

Abstract

The unique qualities of the human brain are a product of a complex evolutionary process. Evolution, famously described by François Jacob as a "tinkerer," builds upon existing genetic elements by modifying and repurposing them for new functions. Genetic changes in DNA may lead to the emergence of new genes or cause altered gene expression patterns. Both gene and regulatory element mutations may lead to new functions. Yet, this process may lead to side-effects. An evolutionary trade-off occurs when an otherwise beneficial change, which is important for evolutionary success and is under strong positive selection, concurrently results in a detrimental change in another trait. Pleiotropy occurs when a gene affects multiple traits. Antagonistic pleiotropy is a phenomenon whereby a genetic variant leads to an increase in fitness at one life-stage or in a specific environment, but simultaneously decreases fitness in another respect. Therefore, it is conceivable that the molecular underpinnings of evolution of highly complex traits, including brain size or cognitive ability, under certain conditions could result in deleterious effects, which would increase the susceptibility to psychiatric or neurodevelopmental diseases. Here, we discuss possible trade-offs and antagonistic pleiotropies between evolutionary change in a gene sequence, dosage or activity and the susceptibility of individuals to autism spectrum disorders and schizophrenia. We present current knowledge about genes and alterations in gene regulatory landscapes, which have likely played a role in establishing human-specific traits and have been implicated in those diseases.

Keywords: ASD; cognition; evolution; psychiatric discorders; schizophrenia.

FIGURE 1

Genetic alterations in loci related to human brain evolution can lead to neuropsychiatric disorders specifically affecting self-awareness and cognition including schizophrenia (SCZ) and autism spectrum disorder (ASD). (A). Human brain is larger and contains more neurons than the brain of our closest living relative the chimpanzee (Pan troglodytes). Evolution led to the enhancement of several features of human brain including cognition and self-awareness. There is also a considerable degree of convergence between genetic changes that underlie brain evolution and loci related to neuropsychiatric disorders. (B). Examples of genetic alterations in the human lineage related at the same time to evolution of SCZ or ASD.