title: African signatures of recent positive selection in human FOXI1.
abstract: 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.
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Institut de Biologia Evolutiva UPF-CSIC, Parc de Recerca Biomèdica de Barcelona, 08003 Barcelona, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Moreno-Estrada
authors.forename: Estel
authors.initials: E
authors.lastname: Aparicio-Prat
authors.forename: Martin
authors.initials: M
authors.lastname: Sikora
authors.forename: Johannes
authors.initials: J
authors.lastname: Engelken
authors.forename: Anna
authors.initials: A
authors.lastname: Ramírez-Soriano
authors.forename: Francesc
authors.initials: F
authors.lastname: Calafell
authors.forename: Elena
authors.initials: E
authors.lastname: Bosch
mesh_terms: D000349:Africa; D044383:Black People / Q000235:genetics*; D057231:Climate Change; D019143:Evolution, Molecular; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012641:Selection, Genetic / Q000235:genetics*
chemical_list: C477894:FOXI1 protein, human; D051858:Forkhead Transcription Factors
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