Location of Repository

Dynamics of a human interparalog gene conversion hotspot

By Elena Bosch, Matthew E. Hurles, Arcadi Navarro and Mark A. Jobling

Abstract

Gene conversion between paralogs can alter their patterns of sequence identity, thus obscuring their evolutionary relationships and affecting their propensity to sponsor genomic rearrangements. The details of this important process are poorly understood in the human genome because allelic diversity complicates the interpretation of interparalog sequence differences. Here we exploit the haploid nature of the Y chromosome, which obviates complicating interallelic processes, together with its known phylogeny, to understand the dynamics of conversion between two directly repeated HERVs flanking the 780-kb AZFa region on Yq. Sequence analysis of a 787-bp segment of each of the HERVs in 36 Y chromosomes revealed one of the highest nucleotide diversities in the human genome, as well as evidence of a complex patchwork of highly directional gene conversion events. The rate of proximal-to-distal conversion events was estimated as 2.4 × 10[superscript -4] to 1.2 × 10[superscript -3] per generation (3.9 × 10[superscript -7] to 1.9 × 10[superscript -6] per base per generation), and the distal-to-proximal rate as about one-twentieth of this. Minimum observed conversion tract lengths ranged from 1 to 158 bp and maximum lengths from 19 to 1365 bp, with an estimated mean of 31 bp. Analysis of great ape homologs shows that conversion in this hotspot has a deep evolutionary history.Peer-reviewedPublisher Versio

Publisher: Cold Spring Harbor Laboratory Press
Year: 2004
DOI identifier: 10.1101/gr.2177404
OAI identifier: oai:lra.le.ac.uk:2381/2050
Journal:

Suggested articles

Preview

Citations

  1. (1993). A de novo pathological point mutation at the 21-hydroxylase locus: Implications for gene conversion in the human genome.
  2. (1985). A human Y-linked DNA polymorphism and its potential for estimating genetic and evolutionary distance.
  3. (2002). A nomenclature system for the tree of human Y-chromosomal binary haplogroups.
  4. (1995). Absence of polymorphism at the ZFY locus on the human Y chromosome.
  5. (2003). Abundant gene conversion between arms of massive palindromes in human and ape Y chromosomes.
  6. (2003). accepted in revised form
  7. (2000). Apolipoprotein E variation at the sequence haplotype level: Implications for the origin and maintenance of a major human polymorphism.
  8. (2002). Are 100,000 “SNPs” useless?
  9. (2013). Conversion Hotspot Genome Research 843 www.genome.org Cold
  10. (2000). Deletion of azoospermia factor a (AZFa) region of human Y chromosome caused by recombination between HERV15 proviruses.
  11. (1999). DnaSP version 3: An integrated program for molecular population genetics and molecular evolution analysis.
  12. (1997). Evidence for gene conversion in the generation of extensive polymorphism in the promoter of the growth hormone gene.
  13. (2001). Gene conversion and different population histories may explain the contrast between polymorphism and linkage disequilibrium levels.
  14. (2003). Gene conversion as a source of nucleotide diversity in Plasmodium falciparum.
  15. (1998). Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits.
  16. (2001). Genomic divergences between humans and other hominoids and the effective population size of the common ancestor of humans and chimpanzees.
  17. (2001). Global patterns of human DNA sequence variation in a 10-kb region on chromosome 1.
  18. (2004). Intense and highly localized gene conversion activity in human meiotic crossover hot spots.
  19. (1995). New HLA-DPB1 alleles generated by interallelic gene conversion detected by analysis of sperm.
  20. (2000). Population genetic implications from sequence variation in four Y chromosome genes.
  21. (2000). Recent common ancestry of human Y chromosomes: Evidence from DNA sequence data.
  22. (2001). Recombination and gene conversion-like events may contribute to ABO gene diversity causing various phenotypes.
  23. (1998). SplitsTree: Analyzing and visualizing evolutionary data.
  24. (1999). Suppression of intrachromosomal gene conversion in mammalian cells by small degrees of sequence divergence.
  25. (2002). The human Y chromosome haplogroup tree: Nomenclature and phylogeny of its major divisions.
  26. (2003). The human Y chromosome: An evolutionary marker comes of age.
  27. (1994). The recombination signal sequence-binding protein RBP-2N functions as a transcriptional repressor.
  28. (1998). The role of gene conversion in determining sequence variation and divergence
  29. Two long homologous retroviral sequence blocks in proximal Yq11 cause AZFa microdeletions as a result of intrachromosomal recombination events.
  30. (2000). Worldwide DNA sequence variation in a 10-kilobase noncoding region on human chromosome 22.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.