title: A human derived SSADH coding variant is replacing the ancestral allele shared with primates.
abstract: BACKGROUND
  A growing number of reports describe markers with high frequencies of the ancestral alleles in Africa, contrasting with high frequencies and possibly fixation of derived variants out of Africa. Such a pattern can be explained by either neutral or non-neutral processes.
  
  
  OBJECTIVE
  The study examined worldwide frequencies of two non-synonymous variants in NAD(+)-dependent succinic semialdehyde dehydrogenase (SSADH), in a search for possible signatures of natural selection favouring the derived alleles.
  
  
  METHODS
  The typing of 1574 subjects were compiled, representing 60 populations from all continents. SSADH haplotype frequencies were correlated across 52 populations to those of 260 single nucleotide polymorphism (SNP) markers deposited in the CEPH database and of markers reported to be under positive Darwinian selection.
  
  
  RESULTS
  In the world population, the c.538C variant is proceeding to replace the ancestral c.538T, shared with primates. The overall population differentiation is within the normal range. A significant correlation was also found between the frequencies of the derived alleles in SSADH and Microcephalin (MCPH1), which showed concerted changes worldwide and, at least in Asian populations, also on a restricted geographical scale.
  
  
  CONCLUSIONS
  The analysis of robust correlations based on a large panel of populations is potentially able to identify clusters of genomic regions or genes showing co-evolution of the frequencies of derived alleles.
authors: Department of Cell Biology, University of Calabria, Rende, Italy.
authors: Ofelia
authors: O
authors: Leone
authors: Paola
authors: P
authors: Blasi
authors: Francesca
authors: F
authors: Palmerio
authors: Andrey I
authors: AI
authors: Kozlov
authors: Patrizia
authors: P
authors: Malaspina
authors: Andrea
authors: A
authors: Novelletto
mesh_terms: D000483:Alleles; D000818:Animals; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011323:Primates / Q000235:genetics*; D050644:Succinate-Semialdehyde Dehydrogenase / Q000235:genetics*
chemical_list: C493643:ALDH5A1 protein, human; D050644:Succinate-Semialdehyde Dehydrogenase