Tracking human migrations by the analysis of the distribution of HLA alleles, lineages and haplotypes in closed and open populations.
The human leucocyte antigen (HLA) system shows extensive variation in the number and function of loci and the number of alleles present at any one locus. Allele distribution has been analysed in many populations through the course of several decades, and the implementation of molecular typing has significantly increased the level of diversity revealing that many serotypes have multiple functional variants. While the degree of diversity in many populations is equivalent and may result from functional polymorphism(s) in peptide presentation, homogeneous and heterogeneous populations present contrasting numbers of alleles and lineages at the loci with high-density expression products. In spite of these differences, the homozygosity levels are comparable in almost all of them. The balanced distribution of HLA alleles is consistent with overdominant selection. The genetic distances between outbred populations correlate with their geographical locations; the formal genetic distance measurements are larger than expected between inbred populations in the same region. The latter present many unique alleles grouped in a few lineages consistent with limited founder polymorphism in which any novel allele may have been positively selected to enlarge the communal peptide-binding repertoire of a given population. On the other hand, it has been observed that some alleles are found in multiple populations with distinctive haplotypic associations suggesting that convergent evolution events may have taken place as well. It appears that the HLA system has been under strong selection, probably owing to its fundamental role in varying immune responses. Therefore, allelic diversity in HLA should be analysed in conjunction with other genetic markers to accurately track the migrations of modern humans.
Department of Pathology, Stanford University, Stanford, CA, USA. marcelof@stanford.edu
Marcelo A
MA
Fernandez Vina
Jill A
JA
Hollenbach
Kirsten E
KE
Lyke
Marcelo B
MB
Sztein
Martin
M
Maiers
William
W
Klitz
Pedro
P
Cano
Steven
S
Mack
Richard
R
Single
Chaim
C
Brautbar
Shosahna
S
Israel
Eduardo
E
Raimondi
Evelyne
E
Khoriaty
Adlette
A
Inati
Marco
M
Andreani
Manuela
M
Testi
Maria Elisa
ME
Moraes
Glenys
G
Thomson
Peter
P
Stastny
Kai
K
Cao
D003710:Demography; D004641:Emigration and Immigration / Q000266:history*; D019143:Evolution, Molecular; D018703:Founder Effect; D005819:Genetic Markers / Q000235:genetics; D014644:Genetic Variation; D005828:Genetics, Population / Q000379:methods*; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D049690:History, Ancient; D006801:Humans; D012641:Selection, Genetic
D005819:Genetic Markers; D006680:HLA Antigens