Cell
Volume 174, Issue 6, 6 September 2018, Pages 1424-1435.e15
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Article
No Evidence for Recent Selection at FOXP2 among Diverse Human Populations

https://doi.org/10.1016/j.cell.2018.06.048Get rights and content
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Highlights

  • No support for positive selection at FOXP2 in large genomic datasets

  • Sample composition and genomic scale significantly affect selection scans

  • An intronic ROI within FOXP2 is expressed in human brain cells and cortical tissue

  • This ROI contains a large amount of constrained, human-specific polymorphisms

Summary

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
human evolution
population structure
natural selection
language
demography
human brain

Cited by (0)

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Present address: Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA

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Present address: Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA

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