Evolution of Human Brain Left–Right Asymmetry: Old Genes with New Functions

Abstract

The human brain is generally anatomically symmetrical, boasting mirror-like brain regions in the left and right hemispheres. Despite this symmetry, fine-scale structural asymmetries are prevalent and are believed to be responsible for distinct functional divisions within the brain. Prior studies propose that these asymmetric structures are predominantly primate-specific or even unique to humans, suggesting that the genes contributing to the structural asymmetry of the human brain might have evolved recently. In our study, we identified approximately 1,500 traits associated with human brain asymmetry by collecting paired brain MRI features from the UK Biobank. Each trait is measured in a specific region of one hemisphere and mirrored in the corresponding region of the other hemisphere. Conducting genome-wide association studies on these traits, we identified over 1,000 quantitative trait loci (QTLs). Around these index single nucleotide polymorphisms (SNPs), we found approximately 200 genes that are enriched in brain-related Gene Ontology terms and are predominantly up-regulated in brain tissues. Interestingly, most of these genes are evolutionarily old, originating just prior to the emergence of Bilateria (bilaterally symmetrical animals) and Euteleostomi (bony vertebrates with a brain), at a significantly higher ratio than expected. Further analyses of these genes reveal a brain-specific up-regulation in humans relative to other mammalian species. This suggests that the structural asymmetry of the human brain has been shaped by evolutionarily ancient genes that have assumed new functions over time.

Strength of spatial correlation between gray matter connectivity and patterns of proto-oncogene and neural network construction gene expression is associated with diffuse glioma survival

“…However, large population-health databases in neuro-oncology do not consistently present tumor laterality, limiting our evaluation of this possibility ( 50 ). Hemispheric asymmetry in neuroanatomic structures ( 51 , 52 ) and gene expression ( 53 ) have been identified, suggesting that tumors arising from contralateral hemispheres may have biologic distinctions that warrant consideration when exploring gene-brain associations.…”

Enigma of Pyramidal Neurons: Chirality-Centric View on Biological Evolution. Congruence to Molecular, Cellular, Physiological, Cognitive, and Psychological Functions

“…After the first convincing evidence, many great studies were conducted to link synaptic hemispheric asymmetry to the function of PyrNs. For all of them, the knowledge of hemisphere-specific soma orientation could be beneficial [138,[254][255][256][257][258][259][260][261][262][263][264][265][266][267].…”