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High recombination rates and hotspots in a Plasmodium falciparum genetic cross

Hongying Jiang1, Na Li2, Vivek Gopalan3, Martine M Zilversmit4, Sudhir Varma3, Vijayaraj Nagarajan3, Jian Li15, Jianbing Mu1, Karen Hayton1, Bruce Henschen1, Ming Yi6, Robert Stephens6, Gilean McVean7, Philip Awadalla8, Thomas E Wellems1 and Xin-zhuan Su1*

Author affiliations

1 Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA

2 MedImmune, 1 MedImmune Way, Gaithersburg, MD 20878, USA

3 Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA

4 Charles-Bruneau Cancerology Centre, University of Montreal, Faculty of Medicine, Ste. Justine Research Centre, 3175 Chemin de Côte-Ste-Catherine, Montreal, Québec H3T 1C5, Canada

5 State Key Laboratory of Stress Cell Biology, School of Life Science, Xiamen University, 422 Siming South Road, Xiamen, Fujian 361005, PR China

6 Advanced Technology Program, SAIC-Frederick, Inc., NCI-Frederick, 430 Miller Drive, Frederick, MD 21702, USA

7 Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, UK

8 Department of Pediatrics, University of Montreal, Faculty of Medicine, Ste. Justine Research Centre, 3175 Chemin de Côte-Ste-Catherine, Montreal, Québec H3T 1C5, Canada

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Citation and License

Genome Biology 2011, 12:R33  doi:10.1186/gb-2011-12-4-r33

Published: 4 April 2011

Abstract

Background

The human malaria parasite Plasmodium falciparum survives pressures from the host immune system and antimalarial drugs by modifying its genome. Genetic recombination and nucleotide substitution are the two major mechanisms that the parasite employs to generate genome diversity. A better understanding of these mechanisms may provide important information for studying parasite evolution, immune evasion and drug resistance.

Results

Here, we used a high-density tiling array to estimate the genetic recombination rate among 32 progeny of a P. falciparum genetic cross (7G8 × GB4). We detected 638 recombination events and constructed a high-resolution genetic map. Comparing genetic and physical maps, we obtained an overall recombination rate of 9.6 kb per centimorgan and identified 54 candidate recombination hotspots. Similar to centromeres in other organisms, the sequences of P. falciparum centromeres are found in chromosome regions largely devoid of recombination activity. Motifs enriched in hotspots were also identified, including a 12-bp G/C-rich motif with 3-bp periodicity that may interact with a protein containing 11 predicted zinc finger arrays.

Conclusions

These results show that the P. falciparum genome has a high recombination rate, although it also follows the overall rule of meiosis in eukaryotes with an average of approximately one crossover per chromosome per meiosis. GC-rich repetitive motifs identified in the hotspot sequences may play a role in the high recombination rate observed. The lack of recombination activity in centromeric regions is consistent with the observations of reduced recombination near the centromeres of other organisms.