Biased Gene Conversion and Its Impact on Genome Evolution


In most eukaryotes, genetic information is exchanged between homologous chromosomes via the process of recombination. As part of this process, short deoxyribonucleic acid (DNA) tracts of less than 1 kb in length are exchanged between chromosomes in an asymmetric fashion in a process known as gene conversion. When such gene conversion events occur within the vicinity of heterozygous loci, this asymmetric exchange of DNA can result in the non‐Mendelian transmission of alleles. Multiple lines of evidence suggest that this non‐Mendelian transmission is biased in favour of G and C alleles at the expense of A and T alleles. This process, known as biased gene conversion, has a number of important implications for understanding the behaviour of alleles within a population and the base composition of the genome itself.

Key Concepts:

  • Biased gene conversion is the preferential transmission of certain alleles to the next generation, arising from asymmetries in the gene conversion process.

  • Biased gene conversion appears to preferentially favour GC alleles over AT alleles, resulting in the overtransmission of GC alleles in regions of high recombination.

  • Biased gene conversion can increase the frequency of an allele in a population.

  • Consistent biased gene conversion can ultimately influence the base composition of the genome, leading to increased levels of GC content.

  • Although a difficult phenomenon to measure, multiple lines of experimental and evolutionary evidence support the existence of biased gene conversion.

Keywords: recombination; biased gene conversion; GC content; evolution; substitution rate

Figure 1.

The effect of biased gene conversion (BGC) on genetic drift. The figure shows the effect of BGC on the frequency of the driven allele over time. Red lines show frequencies simulated with BGC, whereas the black lines show simulations conducted without BGC. Faint lines show five independent simulations in each case, whereas thick lines show the theoretical expectation. Data was simulated for a population size of 10 000 with a starting allele frequency of 5%, and a very strong bias parameter (δ) of 0.5%, chosen for illustration purposes.

Figure 2.

Cartoon representation of a possible biased gene conversion mechanism. A double‐strand break in the vicinity of a G/A polymorphism results in the partial loss of the A/T base pair on the second chromosome. The subsequent heteroduplex formed following strand invasion contains a mispairing between the G and T nucleotides. biased gene conversion results from the biased repair of this mismatch, which tends to favour the G allele over the T allele. © PLoS.

Figure 3.

Increased GC substitution rates around human hotspots. Recombination hotspots are localised regions of approximately 2 kb width in which the recombination rate can be hundreds or thousands of times that of the surrounding region. This figure shows an increased rate of GC substitutions can be observed on the human lineage in the vicinity of human hotspots. However, as recombination hotspot positions are not shared between humans and chimps, no corresponding increase is seen on the chimpanzee lineage. Modified from Auton et al. ().



Auton A, Fledel‐Alon A, Pfeifer S et al. (2012) A fine‐scale chimpanzee genetic map from population sequencing. Science 336(6078): 193–198.

Baudat F, Buard J, Grey C et al. (2010) PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice. Science 327(5967): 836–840.

Bengtsson BO (1986) Biased conversion as the primary function of recombination. Genetical Research 47(1): 77–80.

Berg IL, Neumann R, Sarbajna S et al. (2011) Variants of the protein PRDM9 differentially regulate a set of human meiotic recombination hotspots highly active in African populations. Proceedings of the National Academy of Sciences of the USA 108(30): 12378–12383.

Birdsell JA (2002) Integrating genomics, bioinformatics, and classical genetics to study the effects of recombination on genome evolution. Molecular Biology and Evolution 19(7): 1181–1197.

Brown TC and Jiricny J (1988) Different base/base mispairs are corrected with different efficiencies and specificities in monkey kidney cells. Cell 54(5): 705–711.

Capra JA, Hubisz MJ, Kostka D, Pollard KS and Siepel A (2013) A model‐based analysis of GC‐biased gene conversion in the human and chimpanzee genomes. PLoS Genetics 9(8): e1003684.

Capra JA and Pollard KS (2011) Substitution patterns are GC‐biased in divergent sequences across the metazoans. Genome Biology and Evolution 3: 516–527.

Chen JM, Cooper DN, Chuzhanova N, Ferec C and Patrinos GP (2007) Gene conversion: mechanisms, evolution and human disease. Nature Reviews Genetics 8(10): 762–775.

Coop G and Myers SR (2007) Live hot, die young: transmission distortion in recombination hotspots. PLoS Genetics 3(3): e35.

Dreszer TR, Wall GD, Haussler D and Pollard KS (2007) Biased clustered substitutions in the human genome: the footprints of male‐driven biased gene conversion. Genome Research 17(10): 1420–1430.

Duret L and Arndt PF (2008) The impact of recombination on nucleotide substitutions in the human genome. PLoS Genetics 4(5): e1000071.

Duret L, Eyre‐Walker A and Galtier N (2006) A new perspective on isochore evolution. Gene 385: 71–74.

Duret L and Galtier N (2009) Biased gene conversion and the evolution of mammalian genomic landscapes. Annual Review of Genomics and Human Genetic 10: 285–311.

Duret L, Semon M, Piganeau G, Mouchiroud D and Galtier N (2002) Vanishing GC‐rich isochores in mammalian genomes. Genetics 162(4): 1837–1847.

Galtier N, Duret L, Glemin S and Ranwez V (2009) GC‐biased gene conversion promotes the fixation of deleterious amino acid changes in primates. Trends in Genetics 25(1): 1–5.

Glemin S (2010) Surprising fitness consequences of GC‐biased gene conversion: I Mutation load and inbreeding depression. Genetics 185(3): 939–959.

Hernandez RD, Williamson SH, Zhu L and Bustamante CD (2007) Context‐dependent mutation rates may cause spurious signatures of a fixation bias favoring higher GC‐content in humans. Molecular Biology and Evolution 24(10): 2196–2202.

Hinch AG, Tandon A, Patterson N et al. (2011) The landscape of recombination in African Americans. Nature 476(7359): 170–175.

Jeffreys AJ and Neumann R (2002) Reciprocal crossover asymmetry and meiotic drive in a human recombination hot spot. Nature Genetics 31(3): 267–271.

Jeffreys AJ and Neumann R (2005) Factors influencing recombination frequency and distribution in a human meiotic crossover hotspot. Human Molecular Genetics 14(15): 2277–2287.

Katzman S, Capra JA, Haussler D and Pollard KS (2011) Ongoing GC‐biased evolution is widespread in the human genome and enriched near recombination hot spots. Genome Biology and Evolution 3: 614–626.

Kauppi L, May CA and Jeffreys AJ (2009) Analysis of meiotic recombination products from human sperm. Methods in Molecular Biology 557: 323–355.

Lamb BC (1984) The properties of meiotic gene conversion important in its effects on evolution. Heredity 53(Pt 1): 113–138.

Lartillot N (2013) Phylogenetic patterns of GC‐biased gene conversion in placental mammals and the evolutionary dynamics of recombination landscapes. Molecular Biology and Evolution 30(3): 489–502.

Lesecque Y, Mouchiroud D and Duret L (2013) GC‐biased gene conversion in yeast is specifically associated with crossovers: molecular mechanisms and evolutionary significance. Molecular Biology and Evolution 30(6): 1409–1419.

Mancera E, Bourgon R, Brozzi A, Huber W and Steinmetz LM (2008) High‐resolution mapping of meiotic crossovers and non‐crossovers in yeast. Nature 454(7203): 479–485.

Marais G (2003) Biased gene conversion: implications for genome and sex evolution. Trends in Genetics 19(6): 330–338.

Martini E, Borde V, Legendre M et al. (2011) Genome‐wide analysis of heteroduplex DNA in mismatch repair‐deficient yeast cells reveals novel properties of meiotic recombination pathways. PLoS Genetics 7(9): e1002305.

Montoya‐Burgos JI, Boursot P and Galtier N (2003) Recombination explains isochores in mammalian genomes. Trends in Genetics 19(3): 128–130.

Myers S, Bowden R, Tumian A et al. (2010) Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic recombination. Science 327(5967): 876–879.

Nagylaki T (1983) Evolution of a finite population under gene conversion. Proceedings of the National Academy of Sciences of the USA 80(20): 6278–6281.

Nickoloff JA, Sweetser DB, Clikeman JA, Khalsa GJ and Wheeler SL (1999) Multiple heterologies increase mitotic double‐strand break‐induced allelic gene conversion tract lengths in yeast. Genetics 153(2): 665–679.

Odenthal‐Hesse L, Berg IL, Veselis A, Jeffreys AJ and May CA (2014) Transmission distortion affecting human noncrossover but not crossover recombination: a hidden source of meiotic drive. PLoS Genetics 10(2): e1004106.

Perry J and Ashworth A (1999) Evolutionary rate of a gene affected by chromosomal position. Current Biology 9(17): 987–989.

Ptak SE, Hinds DA, Koehler K et al. (2005) Fine‐scale recombination patterns differ between chimpanzees and humans. Nature Genetics 37(4): 429–434.

Romiguier J, Ranwez V, Douzery EJ and Galtier N (2010) Contrasting GC‐content dynamics across 33 mammalian genomes: relationship with life‐history traits and chromosome sizes. Genome Research 20(8): 1001–1009.

Webster MT and Hurst LD (2012) Direct and indirect consequences of meiotic recombination: implications for genome evolution. Trends in Genetics 28(3): 101–109.

Webster MT, Smith NG, Hultin‐Rosenberg L, Arndt PF and Ellegren H (2005) Male‐driven biased gene conversion governs the evolution of base composition in human alu repeats. Molecular Biology and Evolution 22(6): 1468–1474.

Winckler W, Myers SR, Richter DJ et al. (2005) Comparison of fine‐scale recombination rates in humans and chimpanzees. Science 308(5718): 107–111.

Further Reading

Clement Y and Arndt PF (2013) Meiotic recombination strongly influences GC‐content evolution in short regions in the mouse genome. Molecular Biology and Evolution 30(12): 2612–2618.

Galtier N and Duret L (2007) Adaptation or biased gene conversion? Extending the null hypothesis of molecular evolution. Trends in Genetics 23(6): 273–277.

Spencer CC, Deloukas P, Hunt S et al. (2006) The influence of recombination on human genetic diversity. PLoS Genetics 2(9): e148.

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How to Cite close
Bhérer, Claude, and Auton, Adam(Jun 2014) Biased Gene Conversion and Its Impact on Genome Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020834.pub2]