A Prevalent POLG CAG Microsatellite Length Allele in Humans and African Great Apes

Overview

Journal Mamm Genome

Specialty Genetics

Date 2004 Jun 8

PMID 15181541

Citations 7

Authors

Anja T Rovio

Josef Abel

Arja L Ahola

Aida M Andres

Jaume Bertranpetit

Antoine Blancher

Ronald E Bontrop

Leona G Chemnick

Howard J Cooke

James M Cummins

Heidi A Davis

David J Elliott

Ellen Fritsche

Timothy B Hargreave

Susan M G Hoffman

Anne M Jequier

Shu-Huei Kao

Heui-Soo Kim

David R Marchington

Denise Mehmet

Nel Otting

Joanna Poulton

Oliver A Ryder

Hans-Christian Schuppe

Osamu Takenaka

Yau-Huei Wei

Lars Wichmann

Howard T Jacobs

Affiliations

Soon will be listed here.

Abstract

The human nuclear gene for the catalytic subunit of mitochondrial DNA polymerase gamma ( POLG) contains within its coding region a CAG microsatellite encoding a polyglutamine repeat. Previous studies demonstrated an association between length variation at this repeat and male infertility, suggesting a mechanism whereby the prevalent (CAG)(10) allele, which occurs at a frequency of >80% in different populations, could be maintained by selection. Sequence analysis of the POLG CAG microsatellite region of more than 1000 human chromosomes reveals that virtually all allelic variation at the locus is accounted for by length variation of the CAG repeat. Analysis of POLG from African great apes shows that a prevalent length allele is present in each species, although its exact length is species-specific. In common chimpanzee ( Pan troglodytes) a number of different sequence variants contribute to the prevalent length allele, strongly supporting the idea that the length of the POLG microsatellite region, rather than its exact nucleotide or amino acid sequence, is what is maintained. Analysis of POLG in other primates indicates that the repeat has expanded from a shorter, glutamine-rich sequence, present in the common ancestor of Old and New World monkeys.

Citing Articles

[Mitochondrial diseases and epilepsy].

Cao D Zhongguo Dang Dai Er Ke Za Zhi. 2017; 19(5):502-504.

PMID: 28506337 PMC: 7389136.

The POLG Polyglutamine Tract Variants in Iranian Patients with Multiple Sclerosis.

Khatami M, Heidari M, Mansouri R, Mousavi F Iran J Child Neurol. 2015; 9(1):37-41.

PMID: 25767537 PMC: 4322497.

Mitochondrial DNA polymerase gamma gene polymorphism is not associated with male infertility.

Poongothai J J Assist Reprod Genet. 2013; 30(9):1109-14.

PMID: 23912752 PMC: 3800532. DOI: 10.1007/s10815-013-0058-2.

CAG-repeat variant in the polymerase γ gene and male infertility in the Chinese population: a meta-analysis.

Liu S, Zhang C, Peng H, Yao Y, Shi L, Chen J Asian J Androl. 2010; 13(2):298-304.

PMID: 21102476 PMC: 3739217. DOI: 10.1038/aja.2010.91.

POLG1 polyglutamine tract variants associated with Parkinson's disease.

Eerola J, Luoma P, Peuralinna T, Scholz S, Paisan-Ruiz C, Suomalainen A Neurosci Lett. 2010; 477(1):1-5.

PMID: 20399836 PMC: 2905783. DOI: 10.1016/j.neulet.2010.04.021.

References

Alba M, Santibanez-Koref M, Hancock J . The comparative genomics of polyglutamine repeats: extreme differences in the codon organization of repeat-encoding regions between mammals and Drosophila. J Mol Evol. 2001; 52(3):249-59. DOI: 10.1007/s002390010153. View

Choudhry S, Mukerji M, Srivastava A, Jain S, Brahmachari S . CAG repeat instability at SCA2 locus: anchoring CAA interruptions and linked single nucleotide polymorphisms. Hum Mol Genet. 2001; 10(21):2437-46. DOI: 10.1093/hmg/10.21.2437. View

Kruglyak S, Durrett R, Schug M, Aquadro C . Equilibrium distributions of microsatellite repeat length resulting from a balance between slippage events and point mutations. Proc Natl Acad Sci U S A. 1998; 95(18):10774-8. PMC: 27971. DOI: 10.1073/pnas.95.18.10774. View

Gusmao L, Gonzalez-Neira A, Alves C, Sanchez-Diz P, Dauber E, Amorim A . Genetic diversity of Y-specific STRs in chimpanzees (Pan troglodytes). Am J Primatol. 2002; 57(1):21-9. DOI: 10.1002/ajp.1084. View

Calvas P, Blancher A, Salvignol I, Socha W, RUFFIE J . Length polymorphism of a microsatellite in human and non human primates. C R Acad Sci III. 1994; 317(8):755-63. View

Brinkmann B, Klintschar M, Neuhuber F, Huhne J, Rolf B . Mutation rate in human microsatellites: influence of the structure and length of the tandem repeat. Am J Hum Genet. 1998; 62(6):1408-15. PMC: 1377148. DOI: 10.1086/301869. View

Webster M, Smith N, Ellegren H . Microsatellite evolution inferred from human-chimpanzee genomic sequence alignments. Proc Natl Acad Sci U S A. 2002; 99(13):8748-53. PMC: 124370. DOI: 10.1073/pnas.122067599. View

Ye F, Carrodeguas J, Bogenhagen D . The gamma subfamily of DNA polymerases: cloning of a developmentally regulated cDNA encoding Xenopus laevis mitochondrial DNA polymerase gamma. Nucleic Acids Res. 1996; 24(8):1481-8. PMC: 145809. DOI: 10.1093/nar/24.8.1481. View

van Goethem G, Dermaut B, Lofgren A, Martin J, Van Broeckhoven C . Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Nat Genet. 2001; 28(3):211-2. DOI: 10.1038/90034. View

10.

Liao D, Weiner A . Concerted evolution of the tandemly repeated genes encoding primate U2 small nuclear RNA (the RNU2 locus) does not prevent rapid diversification of the (CT)n.(GA)n microsatellite embedded within the U2 repeat unit. Genomics. 1995; 30(3):583-93. DOI: 10.1006/geno.1995.1280. View

11.

Garza J, Slatkin M, Freimer N . Microsatellite allele frequencies in humans and chimpanzees, with implications for constraints on allele size. Mol Biol Evol. 1995; 12(4):594-603. DOI: 10.1093/oxfordjournals.molbev.a040239. View

12.

Ropp P, Copeland W . Cloning and characterization of the human mitochondrial DNA polymerase, DNA polymerase gamma. Genomics. 1996; 36(3):449-58. DOI: 10.1006/geno.1996.0490. View

13.

Hancock J, Worthey E, Santibanez-Koref M . A role for selection in regulating the evolutionary emergence of disease-causing and other coding CAG repeats in humans and mice. Mol Biol Evol. 2001; 18(6):1014-23. DOI: 10.1093/oxfordjournals.molbev.a003873. View

14.

Holtkemper U, Rolf B, Hohoff C, Forster P, Brinkmann B . Mutation rates at two human Y-chromosomal microsatellite loci using small pool PCR techniques. Hum Mol Genet. 2001; 10(6):629-33. DOI: 10.1093/hmg/10.6.629. View

15.

Spelbrink J, Toivonen J, Hakkaart G, Kurkela J, Cooper H, Lehtinen S . In vivo functional analysis of the human mitochondrial DNA polymerase POLG expressed in cultured human cells. J Biol Chem. 2000; 275(32):24818-28. DOI: 10.1074/jbc.M000559200. View

16.

Lazaruk K, Wallin J, Holt C, Nguyen T, Walsh P . Sequence variation in humans and other primates at six short tandem repeat loci used in forensic identity testing. Forensic Sci Int. 2001; 119(1):1-10. DOI: 10.1016/s0379-0738(00)00388-1. View

17.

Lecrenier N, van der Bruggen P, Foury F . Mitochondrial DNA polymerases from yeast to man: a new family of polymerases. Gene. 1997; 185(1):147-52. DOI: 10.1016/s0378-1119(96)00663-4. View

18.

Goodman M, Porter C, Czelusniak J, Page S, Schneider H, Shoshani J . Toward a phylogenetic classification of Primates based on DNA evidence complemented by fossil evidence. Mol Phylogenet Evol. 1998; 9(3):585-98. DOI: 10.1006/mpev.1998.0495. View

19.

Ellegren H, Primmer C, Sheldon B . Microsatellite 'evolution': directionality or bias?. Nat Genet. 1995; 11(4):360-2. DOI: 10.1038/ng1295-360. View

20.

Rubinsztein D, Amos W, Leggo J, Goodburn S, Jain S, Li S . Microsatellite evolution--evidence for directionality and variation in rate between species. Nat Genet. 1995; 10(3):337-43. DOI: 10.1038/ng0795-337. View