Abstract
To study the evolution of recombination rates in apes, we developed methodology to construct a fine-scale genetic map from high-throughput sequence data from 10 Western chimpanzees, Pan troglodytes verus. Compared to the human genetic map, broad-scale recombination rates tend to be conserved, but with exceptions, particularly in regions of chromosomal rearrangements and around the site of ancestral fusion in human chromosome 2. At fine scales, chimpanzee recombination is dominated by hotspots, which show no overlap with those of humans even though rates are similarly elevated around CpG islands and decreased within genes. The hotspot-specifying protein PRDM9 shows extensive variation among Western chimpanzees, and there is little evidence that any sequence motifs are enriched in hotspots. The contrasting locations of hotspots provide a natural experiment, which demonstrates the impact of recombination on base composition.
MeSH Terms
Animals
Base Sequence
Chromosome Mapping
Chromosomes, Human, Pair 2/genetics
Chromosomes, Mammalian/genetics
CpG Islands
Evolution, Molecular
Female
Genetic Variation
Haplotypes
High-Throughput Nucleotide Sequencing
Histone-Lysine N-Methyltransferase/genetics
Humans
Male
Pan troglodytes/genetics
Polymorphism, Single Nucleotide
Recombination, Genetic
Sequence Analysis, DNA
Species Specificity
Chemicals
Histone-Lysine N-Methyltransferase
PRDM9 protein, human
Authors & Affiliations
23 authors, click to expand affiliations / ORCID
Auton Adam
Wellcome Trust Centre for Human Genetics, Oxford , UK.
Fledel-Alon Adi
Pfeifer Susanne
Venn Oliver
Ségurel Laure
Street Teresa
Leffler Ellen M
Bowden Rory
Aneas Ivy
Broxholme John
Humburg Peter
Iqbal Zamin
Lunter Gerton
Maller Julian
Hernandez Ryan D
Melton Cord
Venkat Aarti
Nobrega Marcelo A
Bontrop Ronald
Myers Simon
Donnelly Peter
Przeworski Molly
McVean Gil
References (31)
31 references, click to expand
-
Prdm9 controls activation of mammalian recombination hotspots.
Science. 2010 Feb 12;327(5967):835
PMID: 20044538
-
Meiotic recombination hot spots and cold spots.
Nat Rev Genet. 2001 May;2(5):360-9
PMID: 11331902
-
Variants of the protein PRDM9 differentially regulate a set of human meiotic recombination hotspots highly active in African populations.
Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12378-83
PMID: 21750151
-
A map of human genome variation from population-scale sequencing.
Nature. 2010 Oct 28;467(7319):1061-73
PMID: 20981092
-
A fine-scale map of recombination rates and hotspots across the human genome.
Science. 2005 Oct 14;310(5746):321-4
PMID: 16224025
-
High-resolution mapping of meiotic crossovers and non-crossovers in yeast.
Nature. 2008 Jul 24;454(7203):479-85
PMID: 18615017
-
A hierarchical combination of factors shapes the genome-wide topography of yeast meiotic recombination initiation.
Cell. 2011 Mar 4;144(5):719-31
PMID: 21376234
-
Comparative linkage-disequilibrium analysis of the beta-globin hotspot in primates.
Am J Hum Genet. 2003 Dec;73(6):1330-40
PMID: 14628290
-
Death of PRDM9 coincides with stabilization of the recombination landscape in the dog genome.
Genome Res. 2012 Jan;22(1):51-63
PMID: 22006216
-
An evolutionary view of human recombination.
Nat Rev Genet. 2007 Jan;8(1):23-34
PMID: 17146469
-
A common sequence motif associated with recombination hot spots and genome instability in humans.
Nat Genet. 2008 Sep;40(9):1124-9
PMID: 19165926
-
The fine-scale structure of recombination rate variation in the human genome.
Science. 2004 Apr 23;304(5670):581-4
PMID: 15105499
-
PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice.
Science. 2010 Feb 12;327(5967):836-40
PMID: 20044539
-
A unifying model for the selective regulation of inducible transcription by CpG islands and nucleosome remodeling.
Cell. 2009 Jul 10;138(1):114-28
PMID: 19596239
-
PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans.
Nat Genet. 2010 Oct;42(10):859-63
PMID: 20818382
-
Biased clustered substitutions in the human genome: the footprints of male-driven biased gene conversion.
Genome Res. 2007 Oct;17(10):1420-30
PMID: 17785536
-
Fine-scale recombination patterns differ between chimpanzees and humans.
Nat Genet. 2005 Apr;37(4):429-34
PMID: 15723063
-
An expanded binding model for Cys2His2 zinc finger protein-DNA interfaces.
Phys Biol. 2011 Jun;8(3):035010
PMID: 21572177
-
Origin of human chromosome 2: an ancestral telomere-telomere fusion.
Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9051-5
PMID: 1924367
-
Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic recombination.
Science. 2010 Feb 12;327(5967):876-9
PMID: 20044541
-
Mammalian recombination hot spots: properties, control and evolution.
Nat Rev Genet. 2010 Mar;11(3):221-33
PMID: 20168297
-
Comparison of fine-scale recombination rates in humans and chimpanzees.
Science. 2005 Apr 1;308(5718):107-11
PMID: 15705809
-
Analysis of chimpanzee history based on genome sequence alignments.
PLoS Genet. 2008 Apr 18;4(4):e1000057
PMID: 18421364
-
Fine-scale recombination rate differences between sexes, populations and individuals.
Nature. 2010 Oct 28;467(7319):1099-103
PMID: 20981099
-
Estimating recombination rates from population-genetic data.
Nat Rev Genet. 2003 Dec;4(12):959-68
PMID: 14631356
-
The landscape of recombination in African Americans.
Nature. 2011 Jul 20;476(7359):170-5
PMID: 21775986
-
Genome-wide analysis reveals novel molecular features of mouse recombination hotspots.
Nature. 2011 Apr 21;472(7343):375-8
PMID: 21460839
-
Ongoing GC-biased evolution is widespread in the human genome and enriched near recombination hot spots.
Genome Biol Evol. 2011;3:614-26
PMID: 21697099
-
The influence of recombination on human genetic diversity.
PLoS Genet. 2006 Sep 22;2(9):e148
PMID: 17044736
-
Absence of the TAP2 human recombination hotspot in chimpanzees.
PLoS Biol. 2004 Jun;2(6):e155
PMID: 15208713
-
A second generation human haplotype map of over 3.1 million SNPs.
Nature. 2007 Oct 18;449(7164):851-61
PMID: 17943122