PMID- 24793785
OWN - NLM
STAT- MEDLINE
DCOM- 20150309
LR  - 20211021
IS  - 2160-1836 (Electronic)
IS  - 2160-1836 (Linking)
VI  - 4
IP  - 7
DP  - 2014 May 2
TI  - Nonsynonymous substitution rate heterogeneity in the peptide-binding region among 
      different HLA-DRB1 lineages in humans.
PG  - 1217-26
LID - 10.1534/g3.114.011726 [doi]
AB  - An extraordinary diversity of amino acid sequences in the peptide-binding region 
      (PBR) of human leukocyte antigen [HLA; human major histocompatibility complex 
      (MHC)] molecules has been maintained by balancing selection. The process of 
      accumulation of amino acid diversity in the PBR for six HLA genes (HLA-A, B, C, 
      DRB1, DQB1, and DPB1) shows that the number of amino acid substitutions in the 
      PBR among alleles does not linearly correlate with the divergence time of alleles 
      at the six HLA loci. At these loci, some pairs of alleles show significantly less 
      nonsynonymous substitutions at the PBR than expected from the divergence time. 
      The same phenomenon was observed not only in the HLA but also in the rat MHC. To 
      identify the cause for this, DRB1 sequences, a representative case of a typical 
      nonlinear pattern of substitutions, were examined. When the amino acid 
      substitutions in the PBR were placed with maximum parsimony on a maximum 
      likelihood tree based on the non-PBR substitutions, heterogeneous rates of 
      nonsynonymous substitutions in the PBR were observed on several branches. A 
      computer simulation supported the hypothesis that allelic pairs with low PBR 
      substitution rates were responsible for the stagnation of accumulation of PBR 
      nonsynonymous substitutions. From these observations, we conclude that the 
      nonsynonymous substitution rate at the PBR sites is not constant among the 
      allelic lineages. The deceleration of the rate may be caused by the coexistence 
      of certain pathogens for a substantially long time during HLA evolution.
CI  - Copyright (c) 2014 Yasukochi and Satta.
FAU - Yasukochi, Yoshiki
AU  - Yasukochi Y
AD  - Molecular and Genetic Epidemiology, Faculty of Medicine, University of Tsukuba, 
      Tsukuba, Ibaraki 305-8575, Japan hyasukou@proof.ocn.ne.jp.
FAU - Satta, Yoko
AU  - Satta Y
AD  - Department of Evolutionary Studies of Biosystems, the Graduate University for 
      Advanced Studies (SOKENDAI), Hayama, Kanagawa 240-0193, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140502
PL  - England
TA  - G3 (Bethesda)
JT  - G3 (Bethesda, Md.)
JID - 101566598
RN  - 0 (Amino Acids)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Peptides)
SB  - IM
MH  - Alleles
MH  - Amino Acids/genetics/metabolism
MH  - Biological Evolution
MH  - Computer Simulation
MH  - *Genetic Heterogeneity
MH  - Genetic Linkage
MH  - Genetic Loci
MH  - HLA-DRB1 Chains/chemistry/classification/*genetics
MH  - Humans
MH  - Kinetics
MH  - Peptides/chemistry/genetics/*metabolism
MH  - Phylogeny
MH  - Protein Binding
PMC - PMC4455771
OTO - NOTNLM
OT  - HLA
OT  - allelic lineage
OT  - balancing selection
OT  - complex genetics
OT  - complex immunity
OT  - genetics of immunity
OT  - infection
OT  - innate immunity
OT  - pathogen
OT  - peptide-binding region
OT  - resistance
OT  - tolerance
EDAT- 2014/05/06 06:00
MHDA- 2015/03/10 06:00
PMCR- 2014/05/02
CRDT- 2014/05/06 06:00
PHST- 2014/05/06 06:00 [entrez]
PHST- 2014/05/06 06:00 [pubmed]
PHST- 2015/03/10 06:00 [medline]
PHST- 2014/05/02 00:00 [pmc-release]
AID - g3.114.011726 [pii]
AID - GGG_011726 [pii]
AID - 10.1534/g3.114.011726 [doi]
PST - epublish
SO  - G3 (Bethesda). 2014 May 2;4(7):1217-26. doi: 10.1534/g3.114.011726.