FOXP2 targets show evidence of positive selection in European populations

Qasim Ayub, Bryndis Yngvadottir, Yuan Chen, Yali Xue, Min Hu, Sonja C Vernes, Simon E Fisher, Chris Tyler-Smith

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)


Forkhead box P2 (FOXP2) is a highly conserved transcription factor that has been implicated in human speech and language disorders and plays important roles in the plasticity of the developing brain. The pattern of nucleotide polymorphisms in FOXP2 in modern populations suggests that it has been the target of positive (Darwinian) selection during recent human evolution. In our study, we searched for evidence of selection that might have followed FOXP2 adaptations in modern humans. We examined whether or not putative FOXP2 targets identified by chromatin-immunoprecipitation genomic screening show evidence of positive selection. We developed an algorithm that, for any given gene list, systematically generates matched lists of control genes from the Ensembl database, collates summary statistics for three frequency-spectrum-based neutrality tests from the low-coverage resequencing data of the 1000 Genomes Project, and determines whether these statistics are significantly different between the given gene targets and the set of controls. Overall, there was strong evidence of selection of FOXP2 targets in Europeans, but not in the Han Chinese, Japanese, or Yoruba populations. Significant outliers included several genes linked to cellular movement, reproduction, development, and immune cell trafficking, and 13 of these constituted a significant network associated with cardiac arteriopathy. Strong signals of selection were observed for CNTNAP2 and RBFOX1, key neurally expressed genes that have been consistently identified as direct FOXP2 targets in multiple studies and that have themselves been associated with neurodevelopmental disorders involving language dysfunction.

Original languageEnglish
Pages (from-to)696-706
Number of pages11
JournalAmerican Journal of Human Genetics
Issue number5
Publication statusPublished - 2 May 2013


  • African Continental Ancestry Group/genetics
  • Algorithms
  • Asian Continental Ancestry Group/genetics
  • Chromatin Immunoprecipitation
  • Databases, Genetic
  • European Continental Ancestry Group/genetics
  • Forkhead Transcription Factors/genetics
  • Humans
  • Membrane Proteins/genetics
  • Nerve Tissue Proteins/genetics
  • RNA Splicing Factors
  • RNA-Binding Proteins/genetics
  • Selection, Genetic/genetics


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