Scan of Human Genome Reveals No New Loci Under Ancient Balancing Selection

Abstract

There has been much speculation as to what role balancing selection has played in evolution. In an attempt to identify regions, such as HLA, at which polymorphism has been maintained in the human population for millions of years, we scanned the human genome for regions of high SNP density. We found 16 regions that, outside of HLA and ABO, are the most highly polymorphic regions yet described; however, evidence for balancing selection at these sites is notably lacking-indeed, whole-genome simulations indicate that our findings are expected under neutrality. We propose that (i) because it is rarely stable, longterm balancing selection is an evolutionary oddity, and (ii) when a balanced polymorphism is ancient in origin, the requirements for detection by means of SNP data alone will rarely be met.

A population genetics study of the Familial Mediterranean Fever gene: evidence of balancing selection under an overdominance regime

“…Balancing selection is thought to be rare in humans; 43,44 up to now most descriptions involve immune response Balancing selection at the MEFV locus M Fumagalli et al loci, 45 with MHC genes probably representing the bestknown example. 46 More recently, genes not directly involved in antigen recognition have been described as targets of balancing selection.…”

How closely does genetic diversity in finite populations conform to predictions of neutral theory? Large deficits in regions of low recombination

“…However, our results reflect only the last 50 generations in a different, captive environment. Analyses indicate that balancing selection probably only affects a small proportion of loci in human genomes (Asthana et al, 2005;Bubb et al, 2006;Andrés et al, 2009) and mice allozyme loci (Storz and Nachman, 2003).…”

Widespread balancing selection and pathogen-driven selection at blood group antigen genes

“…With the aim of identifying loci that have been subjected to natural selection, and following the conundrum whereby selection signatures might extend over relatively short gene regions (due to the action of mutation and recombination; Wiuf et al 2004;Bubb et al 2006), we applied a sliding window approach to all BGA genes (except for ACHE, due to its small size and FUT2, as detailed below) and calculated population genetic differentiation, measured as F ST. Under the assumption of neutrality, F ST is determined by demographic history (i.e., genetic drift and gene flow), which affects all loci similarly.…”

“…Second, summary statistics yielded stronger results for the putative promoter compared to the coding exon. Third, although hitchhiking has the potential to affect large genomic regions, the signatures of balancing selection are predicted to extend over relatively short distances (Wiuf et al 2004;Bubb et al 2006); as an example, the high nucleotide diversity that characterizes the second exon of MHC loci decays rapidly in flanking intronic sequences (Cereb et al 1997;Fu et al 2003) and neighboring exons (Takahata and Sata 1998). This suggests that the departure from neutrality and the high level of nucleotide diversity we observe in the FUT2 putative promoter region is not merely a result of hitchhiking with the coding exon, given the 7 kb separating the transcription start site from the second exon.…”