No Evidence for Recent Selection at FOXP2 among Diverse Human Populations

Cell. 2018 Sep 6;174(6):1424-1435.e15. doi: 10.1016/j.cell.2018.06.048. Epub 2018 Aug 2.

Abstract

FOXP2, initially identified for its role in human speech, contains two nonsynonymous substitutions derived in the human lineage. Evidence for a recent selective sweep in Homo sapiens, however, is at odds with the presence of these substitutions in archaic hominins. Here, we comprehensively reanalyze FOXP2 in hundreds of globally distributed genomes to test for recent selection. We do not find evidence of recent positive or balancing selection at FOXP2. Instead, the original signal appears to have been due to sample composition. Our tests do identify an intronic region that is enriched for highly conserved sites that are polymorphic among humans, compatible with a loss of function in humans. This region is lowly expressed in relevant tissue types that were tested via RNA-seq in human prefrontal cortex and RT-PCR in immortalized human brain cells. Our results represent a substantial revision to the adaptive history of FOXP2, a gene regarded as vital to human evolution.

Keywords: FOXP2; demography; human brain; human evolution; language; natural selection; population structure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Brain / cytology
  • Brain / metabolism
  • Cell Line
  • Databases, Genetic
  • Exons
  • Female
  • Forkhead Transcription Factors / genetics*
  • Genome, Human
  • Haplotypes
  • Humans
  • Introns
  • Male
  • Markov Chains
  • Polymorphism, Single Nucleotide
  • Prefrontal Cortex / metabolism

Substances

  • FOXP2 protein, human
  • Forkhead Transcription Factors