The Heritage of Pathogen Pressures and Ancient Demography in the Human Innate- Immunity CD209/CD209L Region  Luis B. Barreiro, Etienne Patin, Olivier Neyrolles, Howard M. Cann, Brigitte Gicquel, Lluís Quintana-Murci  The American Journal of Human Genetics  Volume 77, Issue 5, Pages 869-886 (November 2005) DOI: 10.1086/497613 Copyright © 2005 The American Society of Human Genetics Terms and Conditions

Figure 1 Scaled diagram of the CD209/CD209L genomic region. Sequenced regions are represented in gray. For CD209, we sequenced a total of 5,500 bp per chromosome, and, for CD209L, 5,391 bp per chromosome. The neck region corresponding to exon 4 and composed of seven coding repeats is also shown. The American Journal of Human Genetics 2005 77, 869-886DOI: (10.1086/497613) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

Figure 2 Inferred haplotypes for CD209 (A) and CD209L (B). The chimpanzee sequence was used to deduce the ancestral state at each position, except for the CD209L positions 1232, 1236, and 1240. For those polymorphisms, the ancestral state was considered to be the most frequent allele. Dark boxes correspond to the derived state at each position. The numbers on the right of the figure indicate the absolute frequency of each haplotype in the different populations studied. Repeat-number variation in the neck region of each gene is reported in the gray columns with the column heads “NR.” Indel polymorphisms are referred as to “1” for insertion and “0” for deletion. The American Journal of Human Genetics 2005 77, 869-886DOI: (10.1086/497613) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

Figure 3 Pairwise D′ LD plots in non-African and African populations. European and East Asian samples were plotted together as “non-Africans” because they showed similar levels of LD (data not shown). Red tags indicate the physical position of each SNP across the genomic region studied. Blue and green lines label the SNPs (MAF>10%) used for CD209 and CD209L, respectively, in the LD plot. For CD209, 47 SNPs presented an MAF>10% in the African sample and 5 in the non-African, whereas, for CD209L, 18 SNPs showed an MAF>10% in Africans and 20 in non-Africans. The high prevalence of SNPs with MAF>10% for CD209 in Africa is due to the presence of the highly divergent cluster A, which presents 35 diagnostic variants with a frequency of 15%. The American Journal of Human Genetics 2005 77, 869-886DOI: (10.1086/497613) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

Figure 4 Estimates of the hotspot intensity (λ) for Africans, Europeans, and East Asians. Estimates of the population recombination rate (ρ) for each population as well as the posterior probabilities of λ>1 and λ>10 are also reported in the key. The American Journal of Human Genetics 2005 77, 869-886DOI: (10.1086/497613) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

Figure 5 Geographical distribution of the neck-region repeat variation in CD209 (A) and CD209L (B). Population codes are (1) Algerians; (2) Mandenka; (3) Yoruba; (4) Biaka Pygmies; (5) Northeastern Bantu from Kenya; (6) Mbuti Pygmies; (7) San; (8) South African Bantu southeastern/southwestern; (9) French and Basque from France; (10) Italian composite from Bergamo, Tuscany, and Sardinia; (11) Orcadian; (12) Russians; (13) Adygei; (14) Middle Eastern composite sample of Druze, Palestinian, and Bedouin; (15) Yakut; (16) Pakistani composite sample; (17) Chinese composite sample; (18) Japanese; (19) Cambodian; (20) Papuan; (21) Melanesian; (22) Pima; (23) Maya; (24) Piapoco and Curripaco; (25) Surui; and (26) Karitiana. For populations 16 and 17, we have pooled the different Pakistani and Chinese individual populations, respectively. For population details of these two composite groups, see the HGDP-CEPH Web site. The American Journal of Human Genetics 2005 77, 869-886DOI: (10.1086/497613) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

Figure 6 CD209 estimated gene tree. Time scale is in MYA. Mutations are represented as black dots and are named for their physical position along CD209. For branches with multiple mutations, order in time is arbitrary. Lineage absolute frequencies in Africa, Europe, and East Asia are reported. The American Journal of Human Genetics 2005 77, 869-886DOI: (10.1086/497613) Copyright © 2005 The American Society of Human Genetics Terms and Conditions

Figure 7 Coalescent-based simulations (2×104) of the expected TMRCA distribution of CD209. The American Journal of Human Genetics 2005 77, 869-886DOI: (10.1086/497613) Copyright © 2005 The American Society of Human Genetics Terms and Conditions