Gene Conversion During Primate Evolution


Gene conversion is a nonreciprocal recombination process; the term originally referred to distorted segregation of alleles in gametocytes. In evolutionary studies, however, gene conversion often means ‘the transfer of deoxyribonucleic acid (DNA) sequence information from one locus to another’. In evolutionary processes, gene conversion is frequently observed between tandemly duplicated sequences or between homologous sequences on the same or on different chromosome(s). Gene conversion between functional loci has three significant roles: (1) Gene conversion generally works to maintain sequence and functional similarity in the ‘coevolution’ of interacting molecules. (2) Gene conversion often takes place between a functional gene and a pseudogene, and such events mainly cause diseases, especially in humans. Rarely, such conversions may confer a novel function to a converted gene. (3) Gene conversion erases advantageous sequence divergence between genes. In these cases, negative selection against for conversion maintains the advantageous divergence, and the converted genes are eliminated from a population.

Key Concepts:

  • Concerted evolution is one of evolutionary mechanisms acting on multigene families, and it maintains homogeneity among members of the family within a species.

  • Coevolution at the molecular level means that two or more molecules that interact with each other evolve in a harmonious way.

  • A nonprocessed pseudogene is a functionless gene caused by detrimental mutations such as nonsense mutations, frameshift mutations (causing a premature stop codon) or mutations in the regulatory region (silencing the expression).

  • A processed pseudogene is a retrotransposed mRNA of a particular gene. They are randomly inserted into the genome and do not have regulatory elements; therefore, they usually are not expressed.

  • Paralogues are homologous genes within a species that originate from gene duplication.

  • Orthologues are homologous genes found in different species that are transmitted to daughter species during speciation.

  • Gametologues are homologous genes on a pair of sex chromosomes, for example, the X and Y chromosomes in mammals or the Z and W chromosomes in birds.

Keywords: diseases‐causing gene conversion; concerted evolution; gene duplication; paired receptors; pseudogenes

Figure 1.

The relationship between recombination and gene conversion. Double DNA strands are depicted as double arrows. The orientation of each arrow indicates a 5′–3′ orientation. When a double‐strand break occurs, a Holliday junction is produced to repair this break. For further repair, the junction moves and produces a heteroduplex. When the heteroduplex is resolved, and depending on the point of the DNA cut (a red arrow at ‘resolution A’ or ‘resolution B’), the outcome is either recombination or gene conversion.

Figure 2.

Sliding window analysis of the number of nucleotide differences (p‐distances) between the HBD and HBB. The sliding window size is 100 bp, and the sliding interval is 10 bp. Depending on the nucleotide differences, the entire gene is divided into four regions. In the schematic below the graph under the X‐axis, boxes and lines represent the positions of exons and introns, respectively.

Figure 3.

Gene organisation of PKD1 and the PKD1 pseudogene clusters in humans and chimpanzees. The length of an arrow roughly represents the size of the respective gene. The orientation of an arrow indicates the orientation of a gene from the 5′–3′ direction. Phylogenies are constructed using the Neighbour‐Joining Method based on p‐distances. A scale bar for each tree is indicated at the bottom of each tree.

Figure 4.

Proposed scenario of gene conversion between the human SIGLEC11 and SIGLEC16P/16 genes. SIGLEC11 and SIGLEC16P/16 are positioned in a head‐to‐head orientation with an approximately 9 kb interval. The arrowhead on SIGLEC16P represents a 4‐bp deletion. The black, grey and white rectangles indicate the exons in the SIGLEC11, SIGLEC16P and SIGLEC16 genes, respectively. The position of ‘exon 1’ is located at the right‐most for SIGLEC11 or the left‐most for both SIGLEC16P and SIGLEC16 in the figure. Reprinted by permission of Oxford University Press from Wang et al. (2012) Figure 9. © Oxford University Press.

Figure 5.

Nucleotide sequence divergences in a palindrome on Xq28. The divergence (ordinate) was examined in a window of 500 bp that did not overlap. The position (abscissa) is relative to the middle of the loop of the palindrome (indicated by a blue arrow). Coloured rectangles at the bottom of the figure indicate the duplicated sequences including the MAGE genes (light pink arrows). The area within the red, dotted line indicates the highly diverged region in MAGE‐A3 and ‐A6. Reproduced from Katsura and Satta . © PloS.



Angata T, Hayakawa T, Yamanaka M, Varki A and Nakamura M (2006) Discovery of Siglec‐14, a novel sialic acid receptor undergoing concerted evolution with Siglec‐5 in primates. FASEB Journal 20: 1964–1973.

Bhowmick BK, Satta Y and Takahata N (2007) The origin and evolution of human ampliconic gene families and ampliconic structure. Genome Research 17: 441–450.

Birot AM, Bouton O, Froissart R, Maire I and Bozon D (1996) IDS gene–pseudogene exchange responsible for an intragenic deletion in a Hunter patient. Human Mutation 8: 44–50.

Bischof JM, Chiang AP, Scheetz TE et al. (2006) Genome‐wide identification of pseudogenes capable of disease‐causing gene conversion. Human Mutation 27: 545–552.

Bogdanova N, Markoff A, Gerke V et al. (2001) Homologues to the fist gene for autosomal dominant polycystic kidney disease are pseudogenes. Genomics 74: 333–341.

Cao H, Lakner U, de Bono B et al. (2008) Siglec 16 encodes a DAP12‐associated receptor expressed in macrophages that evolved from its inhibitory counterpart Siglec 11 and has functional and non‐functional alleles in humans. European Journal of Immunology 38: 2303–2315.

De Marco P, Moroni A, Merello E et al. (2001) Folate pathway gene alterations in patients with neural tube defects. American Journal of Medical Genetics 95: 216–223.

Donohoue PA, Jospe N, Migeon CJ and Dop CV (1989) Two distinct areas of unequal crossing over within the steroid 21‐hydroxylase genes produce absence of CYP21B. Genomics 5: 397–406.

Görlach A, Lee PL, Roesler J et al. (1997) A p47‐phox pseudogene carries the most common mutation causing p47‐phox‐deficient chronic granulomatous disease. Journal of Clinical Investigation 100: 1907–1918.

Hayakawa T, Angata T, Lewis AL et al. (2005) A human‐specific gene in microglia. Science 309: 1693.

Iwase M, Satta Y, Hirai H, Hirai Y and Takahata N (2010) Frequent gene conversion events between the X and Y homologous chromosomal regions in primates. BMC Evolutionary Biology 10: 225–235.

Katsura Y and Satta Y (2011) Evolutionary history of the cancer immunity antigen MAGE gene family. PLoS One 6: e20365.

Koop BF, Siemieniakg D, Slightom JL et al. (1989) Tarsius δ‐ and β‐globin genes: conversions, evolution, and systematic implications. Journal of Biological Chemistry 264: 68–79.

Lahn BT and Page DC (1999) Four evolutionary strata on the human X chromosome. Science 286: 964–967.

Mancuso DJ, Tuley EA, Westfield LA et al. (1991) Human von Willebrand factor gene and pseudogene: structural analysis and differentiation by polymerase chain reaction. Biochemistry 30: 253–269.

Minegishi Y, Coustan‐Smith E, Wang YH et al. (1998) Mutations in the human l5/14 gene resulting B cell deficiency and agammaglobulinemia. Journal of Experimental Medicine 187: 71–77.

Nakashima E, Mabuchi A, Makita Y et al. (2004) Novel SBDS mutations caused by gene conversion in Japanese patients with Shwachman–Diamond syndrome. Human Genetics 114: 345–348.

Nei M and Rooney AP (2005) Concerted and birth‐and‐death evolution of multigene families. Annual Review of Genetics 39: 121–152.

Vanita SV, Reis A, Jung M et al. (2001) A unique form of autosomal dominant cataract explained by gene conversion between beta‐crystallin B2 and its pseudogene. Journal of Medical Genetics 38: 392–396.

Vàzquez‐Salat N, Yuhki N, Beck T, O'Brien SJ and Murphy WJ (2007) Gene conversion between mammalian CCR2 and CCR5 chemokine receptor genes: a potential mechanism for receptor dimerization. Genomics 90: 213–224.

Wang X, Mitra N, Cruz P et al. (2012) Evolution of SIGLEC‐11 and SIGLEC‐16 genes in hominins. Molecular Biology and Evolution 29: 2073–2086.

Watnick TJ, Gandolph MA, Weber H, Neumann HPH and Germino GG (1998) Gene conversion is a likely cause of mutation in PKD1. Human Molecular Genetics 7: 1239–1243.

Zimran A, Sorge J, Gross E et al. (1990) A glucocerebrosidase fusion gene in Gaucher disease: implications for the molecular anatomy, pathogenesis, and diagnosis of this disorder. Journal of Clinical Investigation 85: 219–222.

Further Reading

Bailey JA and Eichler EE (2006) Primate segmental duplications: crucibles of evolution, diversity and disease. Nature Reviews Genetics 7: 552–564.

Balakriev ES and Ayala FJ (2003) Pseudogenes: are they ‘junk’ or functional DNA? Annual Review of Genetics 37: 123–151.

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

Liu Y and West SC (2004) Happy Hollidays: 40th anniversary of the Holliday junction. Nature Reviews Molecular Cell Biology 5: 937–946.

Prado F and Aguilera A (2003) Control of cross‐over by single‐strand DNA resection. Trends in Genetics 19: 428–431.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Satta, Yoko(Jun 2013) Gene Conversion During Primate Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020832.pub2]