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

2. 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

3. 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)

4.
Model of a HLA-B Protein

5. 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

6. 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.

7. 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.

8. 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

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

10. Literature Cited
Abi-Rached, Jobin, Kulkami, McWhinnie, Dalva, Gragert, Babrzadeh, Gharizadeh, Luo, Plummer, Kimani, Carrington, Middleton, Rajalingam, Beksac, Marsh, Maiers, Guethlein, Tavoularis, Little, Green, Norman & Parham “The Shaping of Modern Human Immune Systems by Multiregional Admixture with Archaic Humans.” Science Mag, online.
Freeman, Scott. Biological Science. 4th ed. San Francisco: Person Education, Inc, Print.
Handbook of Statistical Genetics. 3rd ed. Eds. D.J. Balding, M. Bishop., C. Cannings. Chichester: John Wiley & Sons, Ltd, Print.
“Haplotype.” genome.gov. National Human Genome Research Institute. Web. 17 November
McGrath, Matt. “Neanderthal sex boosted immunity in modern humans.” BBC News, online.
Mick, Jason. “Neanderthal Sex Gave Europeans and Asians Stronger Immune Systems.” Daily Tech, online htm 
Rhymer, Judith M and Daniel Simberloff. “Extinction by Hybridization and Introgression.” Annual Reviews Inc., Web November
Sample, Ian. “The Downside of Sex with Neanderthals.” The Guardian, online.
Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. “Functions of natural killer cells.” Nat Immunol, May Web November
Young, Ed. “Did sex with Neanderthals and Denisovans shape our immune system? The jury’s still out.” Discover Magazine, online. denisovans-shape-our-immune-systems-the-jury%E2%80%99s-still-out/