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The red queen model of recombination hotspots evolution in the light of archaic and modern human genomes.

Lesecque Y, Glémin S, Lartillot N, Mouchiroud D, Duret L - PLoS Genet. (2014)

Bottom Line: Recombination is an essential process in eukaryotes, which increases diversity by disrupting genetic linkage between loci and ensures the proper segregation of chromosomes during meiosis.However, the reasons for these changes and the rate at which they occur are not known.Surprisingly, however, our analyses indicate that Denisovan recombination hotspots did not overlap with modern human ones, despite sharing similar PRDM9 target motifs.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Biométrie et Biologie Evolutive, UMR CNRS 5558, Université Lyon 1, Villeurbanne, France.

ABSTRACT
Recombination is an essential process in eukaryotes, which increases diversity by disrupting genetic linkage between loci and ensures the proper segregation of chromosomes during meiosis. In the human genome, recombination events are clustered in hotspots, whose location is determined by the PRDM9 protein. There is evidence that the location of hotspots evolves rapidly, as a consequence of changes in PRDM9 DNA-binding domain. However, the reasons for these changes and the rate at which they occur are not known. In this study, we investigated the evolution of human hotspot loci and of PRDM9 target motifs, both in modern and archaic human lineages (Denisovan) to quantify the dynamic of hotspot turnover during the recent period of human evolution. We show that present-day human hotspots are young: they have been active only during the last 10% of the time since the divergence from chimpanzee, starting to be operating shortly before the split between Denisovans and modern humans. Surprisingly, however, our analyses indicate that Denisovan recombination hotspots did not overlap with modern human ones, despite sharing similar PRDM9 target motifs. We further show that high-affinity PRDM9 target motifs are subject to a strong self-destructive drive, known as biased gene conversion (BGC), which should lead to the loss of the majority of them in the next 3 MYR. This depletion of PRDM9 genomic targets is expected to decrease fitness, and thereby to favor new PRDM9 alleles binding different motifs. Our refined estimates of the age and life expectancy of human hotspots provide empirical evidence in support of the Red Queen hypothesis of recombination hotspots evolution.

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Related in: MedlinePlus

Modern human recombination profiles around HM and CM motifs found in the HC-ancestral sequence.Human historical recombination rates (cM/Mb) around CM (dotted line) and HM (solid line) motifs found in the human-chimpanzee reconstructed ancestral sequence (F2 subset). Recombination rates are averaged on 2 kb overlapping windows (overlap  = 1 kb). The 95% confidence interval of the mean recombination rate is shown by the grey area for HM and the hatched area for CM.
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pgen-1004790-g002: Modern human recombination profiles around HM and CM motifs found in the HC-ancestral sequence.Human historical recombination rates (cM/Mb) around CM (dotted line) and HM (solid line) motifs found in the human-chimpanzee reconstructed ancestral sequence (F2 subset). Recombination rates are averaged on 2 kb overlapping windows (overlap  = 1 kb). The 95% confidence interval of the mean recombination rate is shown by the grey area for HM and the hatched area for CM.

Mentions: We first identified HM motifs (N = 5,704) in the reconstructed autosomal sequences of the human-chimpanzee ancestor (HC), and then counted base replacement changes along the four branches of the phylogeny (hereafter termed modern human, Denisovan, Hominini and chimpanzee branches, Figure 1), by comparing sequences of reference genomes to the ancestral one (see methods). It should be noted that the detected base changes include both fixed and polymorphic mutations. To quantify the excess of base changes (if any) on HM motifs along each branch of the phylogeny, we used as a reference the rate of base change within a control motif (CM: CTTCCCTNNCCAC, N = 5,483), which differs from HM by the second position and does not show any effect on the recombination pattern [30] (Figure 2).


The red queen model of recombination hotspots evolution in the light of archaic and modern human genomes.

Lesecque Y, Glémin S, Lartillot N, Mouchiroud D, Duret L - PLoS Genet. (2014)

Modern human recombination profiles around HM and CM motifs found in the HC-ancestral sequence.Human historical recombination rates (cM/Mb) around CM (dotted line) and HM (solid line) motifs found in the human-chimpanzee reconstructed ancestral sequence (F2 subset). Recombination rates are averaged on 2 kb overlapping windows (overlap  = 1 kb). The 95% confidence interval of the mean recombination rate is shown by the grey area for HM and the hatched area for CM.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230742&req=5

pgen-1004790-g002: Modern human recombination profiles around HM and CM motifs found in the HC-ancestral sequence.Human historical recombination rates (cM/Mb) around CM (dotted line) and HM (solid line) motifs found in the human-chimpanzee reconstructed ancestral sequence (F2 subset). Recombination rates are averaged on 2 kb overlapping windows (overlap  = 1 kb). The 95% confidence interval of the mean recombination rate is shown by the grey area for HM and the hatched area for CM.
Mentions: We first identified HM motifs (N = 5,704) in the reconstructed autosomal sequences of the human-chimpanzee ancestor (HC), and then counted base replacement changes along the four branches of the phylogeny (hereafter termed modern human, Denisovan, Hominini and chimpanzee branches, Figure 1), by comparing sequences of reference genomes to the ancestral one (see methods). It should be noted that the detected base changes include both fixed and polymorphic mutations. To quantify the excess of base changes (if any) on HM motifs along each branch of the phylogeny, we used as a reference the rate of base change within a control motif (CM: CTTCCCTNNCCAC, N = 5,483), which differs from HM by the second position and does not show any effect on the recombination pattern [30] (Figure 2).

Bottom Line: Recombination is an essential process in eukaryotes, which increases diversity by disrupting genetic linkage between loci and ensures the proper segregation of chromosomes during meiosis.However, the reasons for these changes and the rate at which they occur are not known.Surprisingly, however, our analyses indicate that Denisovan recombination hotspots did not overlap with modern human ones, despite sharing similar PRDM9 target motifs.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Biométrie et Biologie Evolutive, UMR CNRS 5558, Université Lyon 1, Villeurbanne, France.

ABSTRACT
Recombination is an essential process in eukaryotes, which increases diversity by disrupting genetic linkage between loci and ensures the proper segregation of chromosomes during meiosis. In the human genome, recombination events are clustered in hotspots, whose location is determined by the PRDM9 protein. There is evidence that the location of hotspots evolves rapidly, as a consequence of changes in PRDM9 DNA-binding domain. However, the reasons for these changes and the rate at which they occur are not known. In this study, we investigated the evolution of human hotspot loci and of PRDM9 target motifs, both in modern and archaic human lineages (Denisovan) to quantify the dynamic of hotspot turnover during the recent period of human evolution. We show that present-day human hotspots are young: they have been active only during the last 10% of the time since the divergence from chimpanzee, starting to be operating shortly before the split between Denisovans and modern humans. Surprisingly, however, our analyses indicate that Denisovan recombination hotspots did not overlap with modern human ones, despite sharing similar PRDM9 target motifs. We further show that high-affinity PRDM9 target motifs are subject to a strong self-destructive drive, known as biased gene conversion (BGC), which should lead to the loss of the majority of them in the next 3 MYR. This depletion of PRDM9 genomic targets is expected to decrease fitness, and thereby to favor new PRDM9 alleles binding different motifs. Our refined estimates of the age and life expectancy of human hotspots provide empirical evidence in support of the Red Queen hypothesis of recombination hotspots evolution.

Show MeSH
Related in: MedlinePlus