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Background  The human  FOXI1  gene codes for a transcription factor involved in the physiology of the inner ear, testis, and kidney. Using three interspecies comparisons, it has been suggested that this may be a gene under human-specific selection. We sought to confirm this finding by using an extended set of orthologous sequences. Additionally, we explored for signals of natural selection within humans by sequencing the gene in 20 Europeans, 20 East Asians and 20 Yorubas and by analysing SNP variation in a 2 Mb region centered on  FOXI1  in 39 worldwide human populations from the HGDP-CEPH diversity panel.    Results  The genome sequences recently available from other primate and non-primate species showed that  FOXI1  divergence patterns are compatible with neutral evolution. Sequence-based neutrality tests were not significant in Europeans, East Asians or Yorubas. However, the Long Range Haplotype (LRH) test, as well as the iHS and XP-Rsb statistics revealed significantly extended tracks of homozygosity around  FOXI1  in Africa, suggesting a recent episode of positive selection acting on this gene. A functionally relevant SNP, as well as several SNPs either on the putatively selected core haplotypes or with significant iHS or XP-Rsb values, displayed allele frequencies strongly correlated with the absolute geographical latitude of the populations sampled.    Conclusions  We present evidence for recent positive selection in the  FOXI1  gene region in Africa. Climate might be related to this recent adaptive event in humans. Of the multiple functions of  FOXI1 , its role in kidney-mediated water-electrolyte homeostasis is the most obvious candidate for explaining a climate-related adaptation.

African signatures of recent positive selection in human FOXI1