• View in gallery

    Comparison of genetic and physical distances of markers on the X chromosome. Gray squares, data from present study; black diamonds, data from Zheng and others.13 Recombination rate is reflected by the slope.

  • View in gallery

    Comparison of genetic13 and physical distances of markers on chromosome 3. Gray line indicates the physical location of the centromere.

  • 1

    Coluzzi M, Sabatini A, Della Torre A, Di Deco MA, Petrarca V, 2002. A polytene chromosome analysis of the Anopheles gambiae species complex. Science 298 :1415–1418.

    • Search Google Scholar
    • Export Citation
  • 2

    Rieseberg LH, 2001. Chromosomal rearrangements and speciation. Trends Ecol Evol 16 :351–358.

  • 3

    Ortiz-Barrientos D, Reiland J, Hey J, Noor MA, 2002. Recombination and the divergence of hybridizing species. Genetica 116 :167–178.

  • 4

    Ayala FJ, Coluzzi M, 2005. Chromosome speciation: humans, Drosophila, and mosquitoes. Proc Natl Acad Sci USA 102 (Suppl 1):6535–6542.

  • 5

    WHO, 2003. World Health Report 2003. Geneva: World Health Organization, 210 pp.

  • 6

    Della Torre A, Tu Z, Petrarca V, 2005. On the distribution and genetic differentiation of Anopheles gambiae s.s. molecular forms. Insect Biochem Mol Biol 35 :755–769.

    • Search Google Scholar
    • Export Citation
  • 7

    Rieseberg LH, Whitton J, Gardner K, 1999. Hybrid zones and the genetic architecture of a barrier to gene flow between two sunflower species. Genetics 152 :713–727.

    • Search Google Scholar
    • Export Citation
  • 8

    Noor MA, Grams KL, Bertucci LA, Reiland J, 2001. Chromosomal inversions and the reproductive isolation of species. Proc Natl Acad Sci USA 98 :12084–12088.

    • Search Google Scholar
    • Export Citation
  • 9

    Feder JL, Roethele JB, Filchak K, Niedbalski J, Romero-Severson J, 2003. Evidence for inversion polymorphism related to sympatric host race formation in the apple maggot fly, Rhagoletis pomonella.Genetics 163 :939–953.

    • Search Google Scholar
    • Export Citation
  • 10

    Butlin RK, 2005. Recombination and speciation. Mol Ecol 14 :2621–2635.

  • 11

    Turner TL, Hahn MW, Nuzhdin SV, 2005. Genomic islands of speciation in Anopheles gambiae.PLoS Biol 3 :e285.

  • 12

    Stump AD, Fitzpatrick MC, Lobo NF, Traore S, Sagnon N, Costantini C, Collins FH, Besansky NJ, 2005. Centromere-proximal differentiation and speciation in Anopheles gambiae.Proc Natl Acad Sci USA 102 :15930–15935.

    • Search Google Scholar
    • Export Citation
  • 13

    Zheng L, Benedict MQ, Cornel AJ, Collins FH, Kafatos FC, 1996. An integrated genetic map of the African human malaria vector mosquito, Anopheles gambiae.Genetics 143 :941–952.

    • Search Google Scholar
    • Export Citation
  • 14

    Holt RA, Subramanian GM, Halpern A, Sutton GG, Charlab R, Nusskern DR, Wincker P, Clark AG, Ribeiro JM, Wides R, Salzberg SL, Loftus B, Yandell M, Majoros WH, Rusch DB, Lai Z, Kraft CL, Abril JF, Anthouard V, Arensburger P, Atkinson PW, Baden H, de Berardinis V, Baldwin D, Benes V, Biedler J, Blass C, Bolanos R, Boscus D, Barnstead M, Cai S, Center A, Chatuverdi K, Christophides GK, Chrystal MA, Clamp M, Cravchik A, Curwen V, Dana A, Delcher A, Dew I, Evans CA, Flanigan M, Grundschober-Freimoser A, Friedli L, Gu Z, Guan P, Guigo R, Hillenmeyer ME, Hladun SL, Hogan JR, Hong YS, Hoover J, Jaillon O, Ke Z, Kodira C, Kokoza E, Koutsos A, Letunic I, Levitsky A, Liang Y, Lin JJ, Lobo NF, Lopez JR, Malek JA, McIntosh TC, Meister S, Miller J, Mobarry C, Mongin E, Murphy SD, O’Brochta DA, Pfannkoch C, Qi R, Regier MA, Remington K, Shao H, Sharakhova MV, Sitter CD, Shetty J, Smith TJ, Strong R, Sun J, Thomasova D, Ton LQ, Topalis P, Tu Z, Unger MF, Walenz B, Wang A, Wang J, Wang M, Wang X, Woodford KJ, Wortman JR, Wu M, Yao A, Zdobnov EM, Zhang H, Zhao Q, Zhao S, Zhu SC, Zhimulev I, Coluzzi M, della Torre A, Roth CW, Louis C, Kalush F, Mural RJ, Myers EW, Adams MD, Smith HO, Broder S, Gardner MJ, Fraser CM, Birney E, Bork P, Brey PT, Venter JC, Weissenbach J, Kafatos FC, Collins FH, Hoffman SL. 2002. The genome sequence of the malaria mosquito Anopheles gambiae.Science 298 :129–149.

    • Search Google Scholar
    • Export Citation
  • 15

    Stump AD, Shoener JA, Costantini C, Sagnon N, Besansky NJ, 2005. Sex-linked differentiation between incipient species of Anopheles gambiae.Genetics 169 :1509–1519.

    • Search Google Scholar
    • Export Citation
  • 16

    Van Ooijen JW, Voorrips RE, 2001. JoinMap® 3.0, Software for the Calculation of Genetic Linkage Maps. Wageningen, The Netherlands: Plant Research International.

  • 17

    Benedict MQ, Rafferty CS, 2002. Unassisted isolated-pair mating of Anopheles gambiae (Diptera: Culicidae) mosquitoes. J Med Entomol 39 :942–944.

    • Search Google Scholar
    • Export Citation
  • 18

    Baker RH, French WL, Kitzmiller JB, 1962. Induced copulation in Anopheles mosquitoes. Mosquito News 22 :16–17.

  • 19

    Nachman MW, 2002. Variation in recombination rate across the genome: evidence and implications. Curr Opin Genet Dev 12 :657–663.

  • 20

    Mahtani MM, Willard HF, 1998. Physical and genetic mapping of the human X chromosome centromere: repression of recombination. Genome Res 8 :100–110.

    • Search Google Scholar
    • Export Citation
  • 21

    Kong A, Gudbjartsson DF, Sainz J, Jonsdottir GM, Gudjonsson SA, Richardsson B, Sigurdardottir S, Barnard J, Hallbeck B, Masson G, Shlien A, Palsson ST, Frigge ML, Thorgeirsson TE, Gulcher JR, Stefansson K, 2002. A high-resolution recombination map of the human genome. Nat Genet 31 :241–247.

    • Search Google Scholar
    • Export Citation
  • 22

    Wu CI, Ting CT, 2004. Genes and speciation. Nat Rev Genet 5 :114–122.

  • 23

    Machado CA, Kliman RM, Markert JA, Hey J, 2002. Inferring the history of speciation from multilocus DNA sequence data: the case of Drosophila pseudoobscura and close relatives. Mol Biol Evol 19 :472–488.

    • Search Google Scholar
    • Export Citation
 
 
 

 

 
 
 

 

 

 

 

 

 

VARIATION IN RECOMBINATION RATE ACROSS THE X CHROMOSOME OF ANOPHELES GAMBIAE

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  • 1 Dipartimento di Scienze di Sanità Pubblica, Università Degli Studi di Roma “La Sapienza,” Rome, Italy; Center for Global Health and Infectious Diseases, Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana

The M and S molecular forms of Anopheles gambiae are considered to be incipient species, despite residual gene exchange. Of the three small genome regions that are strongly differentiated between the molecular forms (“speciation islands”), two are located near centromeres, on the left arm of chromosome 2 and the X chromosome. To test the prediction of reduced recombination in these islands, we estimated recombination rates between microsatellite loci on the X chromosome using two M-form strains. Across most of the chromosome, recombination occurred at ~1 centimorgan per megabase (cM Mb−1), a value closely matching the genome-wide average estimated for A. gambiae and for other eukaryotes. Recombination was much higher at the telomeric end, > 7 cM Mb−1. In the speciation island at the centromeric end, recombination was sharply reduced to ~0.2 cM Mb−1, consistent with a role for reduced recombination in maintaining differentiation between nascent species despite gene flow.

INTRODUCTION

The Anopheles gambiae complex includes seven closely related sibling species showing different degrees of association with humans and major differences in their efficiency at transmitting human malaria parasites. Like a number of other animal and plant taxa that share overlapping ranges and experience some low level of genetic introgression, all except one member of the A. gambiae complex is distinguished by fixed chromosomal arrangements1 that may have facilitated clado-genesis through their limiting effect on recombination.24 A. gambiae sensu stricto (hereafter, A. gambiae), the nominal and most medically important member of the complex, is the principal vector of malaria in Africa, responsible for at least one million deaths and many more clinical episodes annually.5 In West and Central Africa, this species appears to be in the process of further diversification into two assortatively mating “molecular forms” (provisionally named with a non-Linnaean nomenclature as the M and S forms) distinguished by fixed differences in the ribosomal DNA (rDNA) locus.6

In contrast to most full species in the A. gambiae complex, the molecular forms do not differ by fixed inversions. However, the relationship between chromosomal inversions and emerging ecological or reproductive isolation observed in a growing number of taxa79 may be viewed as an example of a more general relationship between recombination and speciation, which is modulated by a variety of genic and chromosomal features that impact recombination, including cen-tromeres.3,10 Indeed, evidence for the involvement of centromeric regions in divergence between molecular forms M and S has been discovered recently.11,12 Significant levels of genetic differentiation seem to be restricted to three genomic “islands,” the largest of which are two pericentromeric regions at the base of the X chromosome and the left arm of chromosome 2, respectively.11,12 However, the only recombination map for A. gambiae,13 constructed with 131 microsatellite markers at an average distance of 1.6 centimorgans (cM), is uninformative for these regions. Herein we have built for the X chromosome, and with emphasis on the centromeric region, a genetic map based on 12 microsatellite markers genotyped for 362 individuals in three families. Reference to the draft genome sequence of A. gambiae14 and integration with the data of Zheng, Benedict, and others13 facilitated improved estimates of the relationship between physical and genetic distances.

MATERIALS AND METHODS

Mosquito crosses.

Single-pair crosses were performed between two laboratory A. gambiae M strains maintained in Rome: GASUA (Xag, 2R+, 2La, 3R+, 3L+ colony from Liberia) and GACAM (Xag, 2R+, 2L+, 3R+, 3L+ colony from Cameroon). To obtain single-pair matings, four virgin GASUA females and a single GACAM male were introduced into an 18-cm3 cage where they were kept for 4 days with access to sugar. Subsequently, the females were blood-fed and allowed to oviposit individually; resulting progeny were reared to adults. Virgin F1 females were backcrossed to GACAM males using the same single-pair method. All P (grandparents), F1 (parents), and backcross progeny were preserved for genotyping. Breeding conditions were 12 hour light/dark photoperiod at 28°C and 90% relative humidity. All specimens were killed by freezing and preserved in tubes over desiccant at room temperature.

DNA extraction and microsatellite analysis.

DNA from individual mosquitoes was extracted using the Wizard SV 96 genomic DNA purification system (Promega, Madison, WI) and resuspended in 50 μL of eluent buffer. The 12 X-linked microsatellite markers used in this study (Table 1) were described previously.13,15 Forward primers were labeled with Beckman-Coulter dyes (D2, D3, and D4; Invitrogen, Carlsbad, CA).

PCR was performed in a GeneAmp 9600 thermal cycler (Applied Biosystems, Foster City, CA) as previously described.15 After PCR, reaction products from up to eight distinct microsatellite loci were pooled, according to the expected non-overlapping size of the products. For each pool, aliquots (0.5–1 μL) of each PCR reaction and 0.3 μL of a 400-bp size standard (Beckman-Coulter, Fullerton, CA) were added to 25 μL of SLS buffer (Beckman-Coulter). PCR products were resolved by capillary electrophoresis on a CEQ8000 System (Beckman-Coulter) according to manufacturer recommendations. Allele sizes were determined using the CEQ8000 fragment analysis software. Genotyping data were analyzed using the Kosambi map function with a LOD threshold of 1 in JoinMap® software, version 3.0.16

RESULTS AND DISCUSSION

A total of 90 single-pair crosses were attempted, of which 27 (30%) resulted in the insemination of at least one female. In 9 cases (10%), the single male was able to inseminate multiple females in the cage. The ability of A. gambiae to mate in laboratory conditions without a swarm is consistent with Benedict and Rafferty.17 The unassisted pair mating method is a major improvement on forcible pair mating,18 a tedious and often unsuccessful procedure that has constrained experimental approaches reliant on individual genetic crosses.

Genotyping of 12 loci was performed for 362 progeny from three backcrosses. In one backcross family, amplification of one of the alleles at locus H503 failed in multiple siblings. To avoid biasing the genetic distance estimates, genotypes for H503 from this one family were omitted from additional data analysis. Genotype data were analyzed separately for each family. Because no inconsistencies in the resulting maps were detected, the data were combined to produce a composite map.

Where sufficient recombination events allowed resolution of genetic map locations, the composite map recapitulated the known physical order of the microsatellite loci (Table 1). However, the recombination rate as a function of physical distance varied widely by position on the X chromosome (Figure 1). Previously, Zheng, Benedict, and others13 noted that markers from divisions 3 and 4 span almost two-thirds of the genetic map of this chromosome. Consistent with their results, H503 and H53 in division 4 are physically < 2 Mb apart but are genetically > 13 cM apart, whereas the loci in pericentromeric divisions 5 and 6 span > 5 Mb of the physical map but < 4 cM on the genetic map. Considering the X chromosome data of Zheng and others13 jointly with those of the present study in the context of the A. gambiae physical map reveals that the recombination rate varies from > 7 cM Mb−1 at the telomeric end of the X to ~0.2 cM Mb−1 in division 6 at the centromeric end.

Both the general pattern and the magnitude of recombination across the acrocentric X chromosome of A. gambiae are consistent with findings from Drosophila and humans.19,20 However, the pattern of elevated recombination at the telomeric end of this chromosome is not found on either arm of chromosome 3 (Figure 2) or on the right arm of chromosome 2 (2R; not shown), based on the data of Zheng and others.13 Mapping the genetic distances against physical distances produces linear relationships for 3L, 3R, and 2R, with very similar recombination rates on all three of these arms (1.3, 1.6, and 1.3 cM Mb−1, respectively). These average recombination rates, and that for the middle of the X (~1 cM Mb−1), are very similar to the average rates for Drosophila (1.5 cM Mb−1)19 and humans (1.1 cM Mb−1).21 Chromosomes 3L, 3R, and 2R, like the X, seem to show strong “centromere effects” on recombination rate (e.g., ~0.2 cM Mb−1 across the centromere of chromosome 3, as judged from the slope in Figure 2). Polymorphism for inversion 2La in back-cross individuals presumably obscured the relationship between genetic distance and physical distance on chromosome 2L.13 Obtaining a detailed map of recombination rates across the A. gambiae genome, well beyond the resources of the present study, will require homokaryotypic and homosequential strains, abundant markers such as single-nucleotide polymorphisms, and a greatly expanded collection of meiotic events.

The M and S forms of A. gambiae are considered to be in the earliest stages of speciation, where ecological and reproductive isolation are present but incomplete. A divergence with gene-flow model predicts that significant differentiation between these taxa should be limited to regions of the genome containing the gene(s) directly responsible for their isolation, with introgression of these genes barred owing to negative fitness consequences for mating or survival.22,23 Assuming the presence of multiple co-adapted genes bearing on ecological and reproductive isolation, their co-localization to regions of low recombination should impede re-assortment and thereby facilitate continuing isolation. Our data have shown that recombination in the M form is reduced by at least 5-fold due to “centromere effects,” to which the speciation island on the X chromosome is subject. Although we did not study the S form or the centric region of chromosome 2L, it is likely that a similar pattern applies. Sequence analysis in the centromere-proximal X chromosome island of M and S molecular forms has revealed an extreme pattern of fixed differences without shared polymorphisms, the converse of the pattern seen outside of the islands.11,12 Both empirical evidence and coalescent simulations using conservatively low (10-fold) reductions in recombination rate and effective population size suggest that the lack of shared polymorphisms in this pericentromeric region cannot be explained by reduced recombination alone, despite its characteristically low levels of variation.11,12 Rejection of neutral evolution implies that selection also is acting against postzygotic incompatibilities, ecological and/or reproductive. Therefore, scanning for the molecular signature of natural selection within the speciation islands should provide a means to identify those genes underlying speciation in A. gambiae.

Table 1

Cytogenetic, physical, and genetic distances of X chromosome microsatellite loci used in this study

Locus*Cytogenetic locationPhysical distance (Mb from telomere)Genetic distance (cM)
* For detailed information on the “H-” and “ND-” loci, see Zheng and others13 and Stump and others,15 respectively.
H5034B1.8259090.000
H534A3.63026713.554
H711w2A9.88494431.648
ND5B15B16.33139237.915
ND5B25B16.40205437.921
ND5C15C17.08896039.503
ND5C25C18.28363639.852
ND5D15D19.25269840.766
ND5D25D19.55621841.036
ND6U2619.92672141.040
ND6U3620.00848841.041
ND6U4622.10429341.379
Figure 1.
Figure 1.

Comparison of genetic and physical distances of markers on the X chromosome. Gray squares, data from present study; black diamonds, data from Zheng and others.13 Recombination rate is reflected by the slope.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 75, 5; 10.4269/ajtmh.2006.75.901

Figure 2.
Figure 2.

Comparison of genetic13 and physical distances of markers on chromosome 3. Gray line indicates the physical location of the centromere.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 75, 5; 10.4269/ajtmh.2006.75.901

*

Address correspondence to Nora J. Besansky, Center for Global Health and Infectious Diseases, Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana. E-mail: nbesansk@nd.edu

These authors contributed equally to this work.

Authors’ addresses: Marco Pombi and Alessandra della Torre, Sezione di Parassitologia, Dipartimento di Scienze di Sanità Pubblica, Università degli Studi di Roma “La Sapienza,” P.le Aldo Moro 5, 00185, Roma, Italy, Telephone: +39-06-4991-4932, Fax: +39-06-4991-4653, E-mails: ale.dellatorre@uniroma1.it and marco.pombi@uniroma1.it. Aram D. Stump and Nora J. Besansky, Center for Global Health and Infectious Diseases, Department of Biological Sciences, Galvin Life Sciences Building, University of Notre Dame, Notre Dame, IN 46556-0369, Telephone: +1-574-631-9321, Fax: +1-574-631-3996, E-mail: nbesansk@nd.edu. Current address for Aram D. Stump: Department of Biology, Williams College, Williamstown, MA 01267, E-mail: Aram.D.Stump@williams.edu.

Acknowledgments: The authors thank Bryan Cassone for assistance with genotyping.

Financial support: This work was supported by the National Institutes of Health (AI63508).

REFERENCES

  • 1

    Coluzzi M, Sabatini A, Della Torre A, Di Deco MA, Petrarca V, 2002. A polytene chromosome analysis of the Anopheles gambiae species complex. Science 298 :1415–1418.

    • Search Google Scholar
    • Export Citation
  • 2

    Rieseberg LH, 2001. Chromosomal rearrangements and speciation. Trends Ecol Evol 16 :351–358.

  • 3

    Ortiz-Barrientos D, Reiland J, Hey J, Noor MA, 2002. Recombination and the divergence of hybridizing species. Genetica 116 :167–178.

  • 4

    Ayala FJ, Coluzzi M, 2005. Chromosome speciation: humans, Drosophila, and mosquitoes. Proc Natl Acad Sci USA 102 (Suppl 1):6535–6542.

  • 5

    WHO, 2003. World Health Report 2003. Geneva: World Health Organization, 210 pp.

  • 6

    Della Torre A, Tu Z, Petrarca V, 2005. On the distribution and genetic differentiation of Anopheles gambiae s.s. molecular forms. Insect Biochem Mol Biol 35 :755–769.

    • Search Google Scholar
    • Export Citation
  • 7

    Rieseberg LH, Whitton J, Gardner K, 1999. Hybrid zones and the genetic architecture of a barrier to gene flow between two sunflower species. Genetics 152 :713–727.

    • Search Google Scholar
    • Export Citation
  • 8

    Noor MA, Grams KL, Bertucci LA, Reiland J, 2001. Chromosomal inversions and the reproductive isolation of species. Proc Natl Acad Sci USA 98 :12084–12088.

    • Search Google Scholar
    • Export Citation
  • 9

    Feder JL, Roethele JB, Filchak K, Niedbalski J, Romero-Severson J, 2003. Evidence for inversion polymorphism related to sympatric host race formation in the apple maggot fly, Rhagoletis pomonella.Genetics 163 :939–953.

    • Search Google Scholar
    • Export Citation
  • 10

    Butlin RK, 2005. Recombination and speciation. Mol Ecol 14 :2621–2635.

  • 11

    Turner TL, Hahn MW, Nuzhdin SV, 2005. Genomic islands of speciation in Anopheles gambiae.PLoS Biol 3 :e285.

  • 12

    Stump AD, Fitzpatrick MC, Lobo NF, Traore S, Sagnon N, Costantini C, Collins FH, Besansky NJ, 2005. Centromere-proximal differentiation and speciation in Anopheles gambiae.Proc Natl Acad Sci USA 102 :15930–15935.

    • Search Google Scholar
    • Export Citation
  • 13

    Zheng L, Benedict MQ, Cornel AJ, Collins FH, Kafatos FC, 1996. An integrated genetic map of the African human malaria vector mosquito, Anopheles gambiae.Genetics 143 :941–952.

    • Search Google Scholar
    • Export Citation
  • 14

    Holt RA, Subramanian GM, Halpern A, Sutton GG, Charlab R, Nusskern DR, Wincker P, Clark AG, Ribeiro JM, Wides R, Salzberg SL, Loftus B, Yandell M, Majoros WH, Rusch DB, Lai Z, Kraft CL, Abril JF, Anthouard V, Arensburger P, Atkinson PW, Baden H, de Berardinis V, Baldwin D, Benes V, Biedler J, Blass C, Bolanos R, Boscus D, Barnstead M, Cai S, Center A, Chatuverdi K, Christophides GK, Chrystal MA, Clamp M, Cravchik A, Curwen V, Dana A, Delcher A, Dew I, Evans CA, Flanigan M, Grundschober-Freimoser A, Friedli L, Gu Z, Guan P, Guigo R, Hillenmeyer ME, Hladun SL, Hogan JR, Hong YS, Hoover J, Jaillon O, Ke Z, Kodira C, Kokoza E, Koutsos A, Letunic I, Levitsky A, Liang Y, Lin JJ, Lobo NF, Lopez JR, Malek JA, McIntosh TC, Meister S, Miller J, Mobarry C, Mongin E, Murphy SD, O’Brochta DA, Pfannkoch C, Qi R, Regier MA, Remington K, Shao H, Sharakhova MV, Sitter CD, Shetty J, Smith TJ, Strong R, Sun J, Thomasova D, Ton LQ, Topalis P, Tu Z, Unger MF, Walenz B, Wang A, Wang J, Wang M, Wang X, Woodford KJ, Wortman JR, Wu M, Yao A, Zdobnov EM, Zhang H, Zhao Q, Zhao S, Zhu SC, Zhimulev I, Coluzzi M, della Torre A, Roth CW, Louis C, Kalush F, Mural RJ, Myers EW, Adams MD, Smith HO, Broder S, Gardner MJ, Fraser CM, Birney E, Bork P, Brey PT, Venter JC, Weissenbach J, Kafatos FC, Collins FH, Hoffman SL. 2002. The genome sequence of the malaria mosquito Anopheles gambiae.Science 298 :129–149.

    • Search Google Scholar
    • Export Citation
  • 15

    Stump AD, Shoener JA, Costantini C, Sagnon N, Besansky NJ, 2005. Sex-linked differentiation between incipient species of Anopheles gambiae.Genetics 169 :1509–1519.

    • Search Google Scholar
    • Export Citation
  • 16

    Van Ooijen JW, Voorrips RE, 2001. JoinMap® 3.0, Software for the Calculation of Genetic Linkage Maps. Wageningen, The Netherlands: Plant Research International.

  • 17

    Benedict MQ, Rafferty CS, 2002. Unassisted isolated-pair mating of Anopheles gambiae (Diptera: Culicidae) mosquitoes. J Med Entomol 39 :942–944.

    • Search Google Scholar
    • Export Citation
  • 18

    Baker RH, French WL, Kitzmiller JB, 1962. Induced copulation in Anopheles mosquitoes. Mosquito News 22 :16–17.

  • 19

    Nachman MW, 2002. Variation in recombination rate across the genome: evidence and implications. Curr Opin Genet Dev 12 :657–663.

  • 20

    Mahtani MM, Willard HF, 1998. Physical and genetic mapping of the human X chromosome centromere: repression of recombination. Genome Res 8 :100–110.

    • Search Google Scholar
    • Export Citation
  • 21

    Kong A, Gudbjartsson DF, Sainz J, Jonsdottir GM, Gudjonsson SA, Richardsson B, Sigurdardottir S, Barnard J, Hallbeck B, Masson G, Shlien A, Palsson ST, Frigge ML, Thorgeirsson TE, Gulcher JR, Stefansson K, 2002. A high-resolution recombination map of the human genome. Nat Genet 31 :241–247.

    • Search Google Scholar
    • Export Citation
  • 22

    Wu CI, Ting CT, 2004. Genes and speciation. Nat Rev Genet 5 :114–122.

  • 23

    Machado CA, Kliman RM, Markert JA, Hey J, 2002. Inferring the history of speciation from multilocus DNA sequence data: the case of Drosophila pseudoobscura and close relatives. Mol Biol Evol 19 :472–488.

    • Search Google Scholar
    • Export Citation
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