The Effect of Mating with Neanderthals and Denisovans on our Immune system Group A10 Gerald Duncan, Olivia Lahay, Madeline Lionberger, Kyle Sledge, Heather Yutko

Introduction HLA (human leukocyte antigen): Genes important in immune system response Haplotype: Combination of alleles transmitted together Ligand: binds to receptors Natural Killer Cells: Integral part of immune system Denisovans: group similar to Neanderthals Balancing selection: Multiple alleles maintained in population Introgression: Gene flow between hybrids and parental populations Admixture: Mixing formerly unexposed populations

Data/Results Study led by Stanford University Human migration from Africa occurred 67,500 years ago  Maximum of  4% of modern Eurasian genomes can be traced back to Neanderthals Maximum of 4-6% of modern Melanesian genomes can be traced back to Denisovans Thousands of alleles per HLA Denisovans would have to evolved certain immunities (Malaria)

http://images.dailytech.com/nimage/21570_large_HLA_B_Protein.jpg Model of a HLA-B Protein

Data/Results (Cont’d) Percentage of HLA-A deviations believed (Abi-Rached)  to be from sexual activity with extinct races: European: 50% Chinese: 70% Papua New Guinean: 95% 50-60 % of Chinese inhabitants possess A*11 Very rare in African regions

Fig. 2 Effect of adaptive introgression of Denisovan HLA class I alleles on modern Asian and Oceanian populations. (A) Simplified map of the HLA class I region showing the positions of the HLA-A, -B, and -C genes. (B) Five of the six Denisovan HLA-A, -B, and -C alleles are identical to modern counterparts. Shown at the left for each allele is the number of sequence reads (4) specific to that allele and their coverage of the ~3.5-kb HLA class I gene. Center columns give the modern-human allele (HLA type) that has the lowest number of single-nucleotide polymorphism (SNP) mismatches to the Denisovan allele. The next most similar modern allele and the number of SNP differences are shown in the columns on the right. ¶A recombinant allele with 5′ segments originating from B*40. §The coding sequence is identical to C*15:05:02. (C and D) Worldwide distributions of the two possible Denisovan HLA-A to -C haplotype combinations. Both are present in modern Asians and Oceanians but absent from sub-Saharan Africans. (E to G) The distribution of three Denisovan alleles: HLA-A*11 (E), C*15 (F), and C*12:02 (G), in modern human populations shows they are common in Asians but absent or rare in sub-Saharan Africans. (H) Estimation of divergence times shows that A*11, C*15, and C*12:02 were formed before the Out-of-Africa migration. Shown on the left are the alleles they diverged from, on the right are the divergence time estimates: median, mean, and range. http://www.sciencemag.org/content/334/6052/89/F2.large.jpg

Fig. 3 Effect of adaptive introgression of Neandertal HLA class I alleles on modern human populations. (A) All six Neandertal HLA-A, -B, and -C alleles are identical to modern HLA class I alleles. Shown at the left for each allele is the number of allele-specific sequence reads (3) and their coverage of the ~3.5-kb HLA gene. Center columns give the modern-human allele (HLA type) having the lowest number of SNP differences from the Neandertal allele. The next most similar modern allele and the number of SNP differences are shown in the columns on the right. Alleles marked with § include additional rare alleles. (B and C) Worldwide distributions of the two possible Neandertal HLA-A to-C haplotype combinations. Both are present in modern Eurasians, but absent from sub-Saharan Africans. (D to G) Distribution of four Neandertal alleles: HLA-B*07:02/03/06 (D), B*51:01/08 (E), C*07:02 (F), and C*16:02 (G), in modern human populations. http://www.sciencemag.org/content/334/6052/89/F3.large.jpg

Discussion The findings suggest: Interbreeding between archaic humans and Homo sapiens. Adaptive introgression of HLA genes. HLA: Control NK cells T cell immunity Highly polymorphic---different alleles Vital immune system component

Conclusion Some HLA alleles in modern humans may have originated from extinct human species. These alleles may contribute to defending against locally prevalent diseases.

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