Behavior Genetics

, Volume 46, Issue 6, pp 754–762 | Cite as

The Unique Evolutionary Signature of Genes Associated with Autism Spectrum Disorder

  • Erez Tsur
  • Michael Friger
  • Idan MenasheEmail author
Original Research


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.


Autism spectrum disorder (ASD) Evolution Exome Negative selection 



The authors are thankful to Dr. Ram Gal for the editing of the manuscript and his useful comments.

Compliance with Ethical Standards

Conflict of Interest

Mr. Erez Tsur declares that he has no conflict of interest. Prof. Michael Friger declares that he has no conflict of interest. Dr. Idan Menashe declares that he has no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

10519_2016_9804_MOESM1_ESM.tif (124 kb)
Figure S1: Venn diagram of the genes associated with autism spectrum disorder 489 (ASD), schizophrenia, Alzheimer’s disease, and asthma (TIFF 124 kb)
10519_2016_9804_MOESM2_ESM.pdf (437 kb)
(PDF 436 kb)
10519_2016_9804_MOESM3_ESM.docx (39 kb)
(DOCX 39 kb)
10519_2016_9804_MOESM4_ESM.pdf (196 kb)
Supplementary material 4 (PDF 197 kb)
10519_2016_9804_MOESM5_ESM.pdf (208 kb)
Supplementary material 5 (PDF 208 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Public Health, Faculty of Health SciencesBen-Gurion University of the NegevBeershebaIsrael
  2. 2.Zlotowski Center for NeuroscienceBen-Gurion University of the NegevBeershebaIsrael

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