Quantification of GC-biased gene conversion in the human genome

Sylvain Glemin (1) , Peter F. Arndt (2) , Messer W. Philip (3) , Petrov M. Dmitri (4) , Nicolas Galtier (1) , L. Duret (5)

1 UMR ISEM - Institut des Sciences de l'Evolution de Montpellier
2 MPIMG - Max Planck Institute for Molecular Genetics
3 Cornell University [New York]
4 Stanford University
5 BPGE - Bioinformatique, phylogénie et génomique évolutive

Much evidence indicates that GC-biased gene conversion (gBGC) has a major impact on the evolution of mammalian ge-nomes. However, a detailed quantification of the process is still lacking. The strength of gBGC can be measured from the analysis of derived allele frequency spectra (DAF), but this approach is sensitive to a number of confounding factors. In particular, we show by simulations that the inference is pervasively affected by polymorphism polarization errors and by spatial heterogeneity in gBGC strength. We propose a new general method to quantify gBGC from DAF spectra, incorporating polarization errors, taking spatial heterogeneity into account, and jointly estimating mutation bias. Applying it to human polymorphism data from the 1000 Genomes Project, we show that the strength of gBGC does not differ between hypermutable CpG sites and non-CpG sites, suggesting that in humans gBGC is not caused by the base-excision repair machinery. Genome-wide, the intensity of gBGC is in the nearly neutral area. However, given that recombination occurs primarily within recombination hotspots, 1%-2% of the human genome is subject to strong gBGC. On average, gBGC is stronger in African than in non-African populations, reflecting differences in effective population sizes. However, due to more heterogeneous recombination landscapes, the fraction of the genome affected by strong gBGC is larger in non-African than in African populations. Given that the location of recombination hotspots evolves very rapidly, our analysis predicts that, in the long term, a large fraction of the genome is affected by short episodes of strong gBGC.

Domaines: Génomique, Transcriptomique et Protéomique [q-bio.GN]; Systématique, phylogénie et taxonomie; Génétique des populations [q-bio.PE]

Sylvain Glemin, Peter F. Arndt, Messer W. Philip, Petrov M. Dmitri, Nicolas Galtier, et al.. Quantification of GC-biased gene conversion in the human genome. Genome Research, 2015, 25 (8), pp.1215 - 1228. ⟨10.1101/gr.185488.114⟩. ⟨hal-01900676⟩