The Unique Evolutionary Signature of Genes Associated with Autism Spectrum Disorder

Behav Genet. 2016 Nov;46(6):754-762. doi: 10.1007/s10519-016-9804-4. Epub 2016 Aug 11.


Autism spectrum disorder (ASD) is a common heritable neurodevelopmental disorder, which is characterized by communication and social deficits that reduce the reproductive fitness of individuals with the disorder. Here, we studied the genomic characteristics of 651 ASD genes in a whole-exome sequencing dataset, to search for traces of the evolutionary forces that helped maintain ASD in the human population. We show that ASD genes are ~65 longer and ~20 % less variable than non-ASD genes. The mutational shortage in ASD genes was particularly eminent when considering only deleterious genetic variations, which is a hallmark of negative selection. We further show that these genomic characteristics are unique to ASD genes, as compared with brain-specific genes or with genes of other diseases. Our findings suggest that ASD genes have evolved under complex evolutionary forces, which have left a unique signature that can be used to identify new candidate ASD genes.

Keywords: Autism spectrum disorder (ASD); Evolution; Exome; Negative selection.

MeSH terms

  • Autism Spectrum Disorder / genetics*
  • Biological Evolution*
  • Genome, Human
  • Humans
  • Models, Genetic
  • Multivariate Analysis
  • ROC Curve
  • Selection, Genetic