Heirs of the jaguar and the anaconda: HLA, conquest and disease in the indigenous populations of the Americas

Cadavid, Luis F.; Watkins, David I.

doi:10.1111/j.1399-0039.1997.tb02865.x

Cited by 16 publications

(13 citation statements)

References 78 publications

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“…This pattern may be the consequence of balancing selection in the form of asymmetric heterozygous advantage [56], where individuals carrying distantly related alleles would benefit from a better immunological protection than homozygous ones [57], [58], [59]. Natural selection favoring functionally effective HLA phenotypes would thus explain why populations with reduced HLA genetic diversity may survive, which is in agreement with two previous studies focusing on Amerindians [40], [60]. Of course, our approach is based on the assumption that alleles greatly differing at the DNA level in PBR coding exons cover a larger antigenic repertoire than closely related ones, which has to be confirmed.…”

Section: Discussionsupporting

confidence: 87%

“…The first objective of this study was to determine whether the molecular profiles of HLA genetic diversity among human populations (the molecular approach) were congruent or not with those based only on frequency data for the same polymorphism (the allelic approach) [19], [20], [22], [24], [25], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50]. Our results suggest that this is the case at the global scale.…”

Section: Discussionmentioning

confidence: 99%

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HLA DNA Sequence Variation among Human Populations: Molecular Signatures of Demographic and Selective Events

2011

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Molecular differences between HLA alleles vary up to 57 nucleotides within the peptide binding coding region of human Major Histocompatibility Complex (MHC) genes, but it is still unclear whether this variation results from a stochastic process or from selective constraints related to functional differences among HLA molecules. Although HLA alleles are generally treated as equidistant molecular units in population genetic studies, DNA sequence diversity among populations is also crucial to interpret the observed HLA polymorphism. In this study, we used a large dataset of 2,062 DNA sequences defined for the different HLA alleles to analyze nucleotide diversity of seven HLA genes in 23,500 individuals of about 200 populations spread worldwide. We first analyzed the HLA molecular structure and diversity of these populations in relation to geographic variation and we further investigated possible departures from selective neutrality through Tajima's tests and mismatch distributions. All results were compared to those obtained by classical approaches applied to HLA allele frequencies.Our study shows that the global patterns of HLA nucleotide diversity among populations are significantly correlated to geography, although in some specific cases the molecular information reveals unexpected genetic relationships. At all loci except HLA-DPB1, populations have accumulated a high proportion of very divergent alleles, suggesting an advantage of heterozygotes expressing molecularly distant HLA molecules (asymmetric overdominant selection model). However, both different intensities of selection and unequal levels of gene conversion may explain the heterogeneous mismatch distributions observed among the loci. Also, distinctive patterns of sequence divergence observed at the HLA-DPB1 locus suggest current neutrality but old selective pressures on this gene. We conclude that HLA DNA sequences advantageously complement HLA allele frequencies as a source of data used to explore the genetic history of human populations, and that their analysis allows a more thorough investigation of human MHC molecular evolution.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

HLA DNA Sequence Variation among Human Populations: Molecular Signatures of Demographic and Selective Events

2011

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“…These alleles are being analysed in the context of peptide anchoring sites. 45,60,61 This is the first study looking at TAP polymorphism in a Mexican Indian population and in the admixed population, the Mestizos, who are the prevalent ethnic group in Mexico. We also compared the TAP gene profile in Mexicans with the one found in other populations of the American Continent, to get a better understanding on the origin of these genes in Mexicans and on their contribution to the MHC pattern.…”

Section: Discussionmentioning

confidence: 99%

“…The well documented history of the different peoples that settled along the American Continent demonstrated that these groups were relatively small in number. 45,49,59,60 This may have been the major cause of the restricted class II pattern.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, the analysis of the genetic profile in different ethnic groups and in some species such as chimpanzee, gorilla, rat and mouse 44 was essential to unravel the origin of polymorphism and to understand the evolution mechanisms of these loci. 45 Analyses in these species demonstrated that TAP1*0101 is not an ancestral human allele although it is prevalent in most populations. 44 The investigation of TAP gene polymorphism using a combination of PCR-based techniques including single-strand conformation polymorphisms (SSCP), restriction fragment length polymorphism (RFLP), nucleotide sequencing and PCR with sequence-specific primers (SSP) in different populations suggest there are some new polymorphic positions in addition to those described here.…”

Section: Introductionmentioning

confidence: 94%

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