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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.
Aim: 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.
Subjects and 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.
Conclusion: 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.