We studied the possible effects of climatic-geographic factors on the world distribution of the mutant allele for the chemokine receptor gene CCR5, which has a 32-bp deletion (CCR5Δ32) preventing cell invasion by the primary transmitting strain of HIV-1. New data on CCR5 polymorphisms in Russian, Ukrainian, and Moldavian populations are presented. All available data on CCR5Δ32 frequencies in the Old World (number of populations n = 77) were used for construction of a geographical gene map to analyze possible correlations between allele frequencies and eight climatic-geographic parameters. A strong positive correlation was found between the allele frequency and latitude (r = 0.72), a strong negative correlation with annual radiation balance (r = –0.66), and a weaker negative correlation with longitude (r = –0.34). Partial correlations were calculated excluding the influence of latitude. The negative correlation between the allele frequency and annual radiation balance decreased (r = –0.42), but remained large and significant. We propose that the existence of correlations between the cline of CCR5Δ32 frequencies and climatic-geographic parameters provides evidence for a possible effect of either natural environmental factors or large-scale population movements on the distribution of this allele.

1.
Alrhatib G, Combadiere C, Brader CC, Fend Y, Kennedy PE, Murphy PM, Berger EA: CC-CCR5:A RANTES, MIP1α, MIP1β receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 1996;272:1955–1958.
2.
Choe H, Farzan M, Sun Y, Sullivan N, Rollins B, Ponath PD, Wu L, Mackay CR, LaRosa G, Newman W, Gerard N, Gererd C, Sodroski J: The β-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 1996;85:1135–1148.
3.
Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill SM, Davis CB, Peiper SC, Schall TJ, Littman DR, Landau NR: Identification of a major co-receptor for primary isolates of HIV-1. Nature 1996;381:661–666.
4.
Doranz BJ, Rucker J, Yi Y, Smyth RJ, Samson M, Peiper S, Parmentier M, Collman RG, Doms RW: A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptor CKR-5, CKR-3 and CKR-2b as fusion cofactors. Cell 1996;85:1149–1158.
5.
Dragic T, Litwin V, Allaway GP, Martin SR, Huang Y, Nagashima KA, Cayanan C, Maddon PJ, Koup RA, Moore JP, Paxton WA: HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 1996;381:667–673.
6.
Feng Y, Broder CC, Kennedy PE, Berder EA: HIV-1 entry cofactor: Functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 1996;272:872–877.
7.
Samson M, Soularue P, Vassart G, Parmentier M: The genes encoding the human CC-chemokine receptor CC-CKR1 to 5 are clustered in the p21.3-p24 region of chromosome 3. Genomics 1996;36:522–526.
8.
Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R, Goedert JJ, Buchbinder SP, Vittinghott E, Gomperts E, Donfield S, Vlahov D, Kaslow R, Saah A, Rinaldo C, Detels R, Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study, O’Brien SJ: Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CCR5 structural gene. Science 1996;273:1856–1862.
9.
Huang Y, Paxton WA, Wolinsky SM, Neumann AU, Zhang L, He T, Kang S, Ceradini D, Jin Z, Yazdanbakhsh K, Kunstman K, Erickson D, Dragon E, Landau NR, Phair J, Ho DD, Koup RA: The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med 1996;2:1240–1243.
10.
Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, Mac-Donald ME, Stuhlmann H, Koup RA, Landau NR: Homozygous defect in HIV-1 coreceptor accounts for resistance to some multiply-exposed individuals to HIV-1 infection. Cell 1996;86:367–377.
11.
Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Saragosti S, Lapoumeroulie C, Cognaux J, Forceille C, Muyldermans G, Verhofstede C, Burtonboy G, Georges M, Imai T, Rana S, Yi Y, Smyth RJ, Collman RG, Doms RW, Vassart G, Parmentier M: Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 1996;382:722–725.
12.
Martinson JJ, Chapman NH, Rees DC, Liu Y-T, Clegg JB: Global distribution of the CCR5 gene 32-basepair deletion. Nat Genet 1997;16:100–103.
13.
Libert F, Cochaus P, Beckman G, Samson M, Aksenova M, Cao A, Czeizel A, Claustres M, Rua C, Ferrari M, Ferrec C, Glover G, Grinde B, Guran S, Kucinskas V, Lavinha J, Mercier B, Ogur G, Peltonen L, Rosatelli C, Schwartz M, Spitsyn V, Timar L, Beckman L, Parmentier M, Vassart G: The ΔCCR5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe. Hum Mol Genet 1998;7:399–406.
14.
Slominsky PA, Shadrina MI, Spitsyn VA, Mikulich AI, Khusnutdinova EK, Limborska SA: A simple and rapid method for determining a 32-bp deletion in the gene for the chemokine receptor CCR5. Russian J Genet 1997;33:1596–1598.
15.
Balanovskaya EV, Nurbaev SD, Rychkov YuG: Computer technology of gene-geographic analysis of a gene pool. I. Statistical information of a gene-geographic map. Russian J Genet 1994;30:951–965.
16.
Balanovskaya EV, Nurbaev SD, Rychkov YuG: Computer technology of gene-geographic analysis of a gene pool. II. Statistical transformation of maps. Russian J Genet 1994;30:1538–1555.
17.
Balanovskaya EV, Nurbaev SD: Computer technology of gene-geographic analysis of a gene pool. III. Derivation of trend surfaces. Russian J Genet 1995;31:536–559.
18.
Cavalli-Sforza LL, Menozzi P, Piazza A: History and Geography of Human Genes. Princeton, Princeton University Press 1995, p 1069.
19.
Sokal RR, Oden NL, Thomson BA: A problem with synthetic maps. Hum Biol 1999;71:1–13.
20.
Physico-geographical World Atlas. Moscow, 1965, p 295.
21.
Chikhi L, Destro-Bisol G, Bertorelle G, Pascali V, Barbujani G: Clines of nuclear DNA markers suggest a largely Neolithic ancestry of the European gene pool. Proc Natl Acad Sci USA 1998;95:9053–9058.
22.
Sokal RR, Oden NL, Wilson C: Genetic evidence for the spread of agriculture in Europe by demic diffusion. Nature 1991;351:143.
23.
Piazza A, Menozzi P, Cavalli-Sforza LL: The HLA-A,B gene frequencies in the world: Migration or selection? Hum Immunol 1980;1:297–304.
24.
Piazza A, Menozzi P, Cavalli-Sforza LL: Synthetic gene frequency maps of man and selective effects of climate. Proc Natl Acad Sci USA 1981;78:2638–2642.
25.
Calafell F, Bertranpetit J: Mountains and genes: Population history of the Pyrénées. Hum Biol 1994;66:823–842.
26.
Aseev MV, Shawi A, Dean M, Baranov VS: Population features of gene mutation frequency of the CKR-5 receptor, determining sensitivity to the AIDS virus. Russian J Genet 1997;33:1724–1726.
27.
Galeeva AR, Khusnutdinova EK, Slominsky PA, Limborska SA: Distribution of the CCR5 chemokine receptor-gene 32-bp deletion in population of Volga-Ural region. Russian J Genet 1998;34:1160–1162.
28.
Stephens JC, Reich DE, Goldstein DB, Shin HD, Smith MW, Carrington M, Winkler C, Huttley G, Allikmets R, Schriml L, Gerrard B, Malasky M, Ramos MD, Morlot S, Tzetis M, Oddoux C, Giovine FS, Nasioulas G, Chandler D, Aseev M, Hanson M, Kalaydjieva L, Glavac D, Gasparini P, Kanavakis E, Claustres M, Kambouris M, Ostrer H, Duff G, Baranov V, Sibul H, Metspalu A, Goldman D, Martin N, Duffy D, Schmidtke J, Estivill X, O’Brien SJ, Dean M: Dating the origin of the CCR5-Δ32 AIDS-resistance allele by the coalescence of haplotypes. Am J Hum Genet 1998;62:1507–1515.
29.
Lucotte G, Mercier G: Δ32 mutation frequencies of the CCR5 coreceptor in different French regions. Life Sci 1998;321:409–413.
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