Issue link: https://ahint.epubxp.com/i/501645
14 ASHI Quarterly First Quarter 2015 S C I E N T I F I C C O M M U N I C A T I O N S Figure 4. HLA and Human Migration Figure 4. The speed of human migration and the resolution of HLA typing were slow/low then, while now, in the jet and supersonic age and high throughput HLA sequencing technologies, the speed of human migrations and HLA typing are fast with better navigation and resolutions! 3. Determination of ethnic origin of individuals in a given population. Studies by Alvarez et al, used HLA class I typing data on 604 individuals living in Montevideo and other places in Uruguay to verify the hypothesis that, while most of the Uruguayan population is of Caucasoid origin, there are also strong indications of the presence of African American and American Indian ancestry in the population 8 Several such studies using HLA haplotype and allele distributions are available at https://mathildasanthropologyblog wordpress com 9 These blog articles, though not peer reviewed, point toward the potential of HLA haplotypes and alleles in a country or geographic region with multiple ethnicities for tracing their origin and time of entry into a particular region or country 4. HLA in forensic anthropology. The utility of HLA typing in solving a forensic anthropology case is illustrated by one anecdotal case by Erlich and Calloway In reporting the case, they dealt with the Mammoth Lakes police department to solve the identity of a murder victim 10 The police wanted to know if the authors' laboratory could help identify a murder victim estimated to have been dead for 6–9 months, who was discovered in a shallow grave in the Shady Rest campground in Mammoth Lakes in the mountains of Southern California While the skeletal remains examined by a forensic anthropologist indicated an Asian female, a preliminary DNA analysis by DNAPrint Genomics (Sarasota, Florida) suggested a possible Native American origin The authors used the HLA typing tool and determined that the genotypes were B*3905/*3905, DRB1*0407/*0407, and DQB1*0302/*0302, indicating the individual was homozygous for each HLA locus typed Interestingly, the frequency of this genotype is extremely rare in most populations (<0 01 percent for DRB1 and DQB1) while it is much higher in Mexican Native American populations (20–30 percent for a Mayan population) and Central American Native American populations With respect to the North American Native American population, the genotype frequency is calculated to be 1–2 percent for Native Americans and among various Asian populations the genotype frequency ranged from 0 01-0 04 percent Similarly, the observed HLA-B genotype (*39:05/*39:05) of the DNA sample is also known to be more prevalent in Native Americans from Mexico and Central America than in other parts of the world So it appears that the murder victim was most likely to be of a Native American origin as indicated by the DNAPrint analysis 10 5. HLA-immune system-anthropology: closing the circle. We started with the basic function of HLA, which is, in essence, to guide the immune response to recognize self from non- self and allow the individual's immune response to be well equipped to deal with ever-evolving pathogens as well as with altered self-antigens (cancer and autoimmune diseases) An elegant research article by Abi-Rached et al, published in Science in 2011, highlights the connection between the basic functions of HLA, the reason for the extreme polymorphisms, and its anthropological significance 11 These authors' findings address the fundamental role of HLA in the adaptive immune response as it is connected to the biological anthropological issue of the selective advantages of admixture of genes by interbreeding As the authors state in the article, there has been a very long debated biological anthropological question as to whether interbreeding between archaic and modern humans occurred Current thinking favors that Neanderthals contributed 1–4 percent to modern Eurasian genomes and Denisovans, a likely sister group to the Neanderthals, contributed 4–6 percent to modern Melanesian genomes 12,13 based on statistical genome-wide comparisons However, these studies did not determine whether there was selected introgression of functionally advantageous genes These authors investigated whether the highly polymorphic HLA Class I genes (HLA-A, B, and C) are more reliable indicators of such an admixture because of their vital roles in immune defense and reproduction as ligands for T cell and natural killer (NK) cell receptors Maintenance of a variety of HLA-A, B, and C proteins could potentially increase the diversity in immune responses generated The ability to counteract such foreign antigenic attacks with versatility in an immune response is certainly critical for long-term human survival 14 HLA-B*73:01 is an exceptionally divergent allele 15,16 A comparison with >2,000 other HLA-B alleles and chimpanzee and gorilla alleles from the same locus (MHC-B) shows that HLA-B*73:01 is most closely related to subsets of chimpanzee and gorilla MHC-B alleles HLA-B*73:01 combines ancient sequence divergence with modern sequence homogeneity – properties compatible with modern humans having recently acquired HLA-B*73:01 through introgression There is an interesting anecdotal report suggesting that while migrating out of Africa, modern humans encountered archaic humans, who resided in Eurasia for more than 200,000 years and who possessed an immune system better adapted to local pathogens 17 Data show that such positive adaptations involved variations in HLA Class I genes exemplified by the modern human populations of the Americas 18,19 For example, HLA-A*11, a frequent archaic allotype in modern Asian populations, is said to be unique in providing T cell-mediated protection against some strains of Epstein-Barr virus (EBV) 20 As we are beginning to learn the full potential of killer immunoglobulin-like receptors (KIR) and their role in NK cell functional activity, it is interesting to note that some of the introgressed HLA Class I genes are good KIR ligands; we know there are inhibitory and activating KIRs and one would assume that from the evolutionary point of view, we would expect the best ligand receptor combinations to have advantages over lesser receptor ligand combinations So based on Human Migrations—Now Human Migration—Then HLA Now: A*02:01—A*02:417 and Counting HLA Then: A2