PMID- 10563013
OWN - NLM
STAT- MEDLINE
DCOM- 19991208
LR  - 20240109
IS  - 0737-4038 (Print)
IS  - 0737-4038 (Linking)
VI  - 16
IP  - 10
DP  - 1999 Oct
TI  - A method for detecting positive selection at single amino acid sites.
PG  - 1315-28
AB  - A method was developed for detecting the selective force at single amino acid 
      sites given a multiple alignment of protein-coding sequences. The phylogenetic 
      tree was reconstructed using the number of synonymous substitutions. Then, the 
      neutrality was tested for each codon site using the numbers of synonymous and 
      nonsynonymous changes throughout the phylogenetic tree. Computer simulation 
      showed that this method accurately estimated the numbers of synonymous and 
      nonsynonymous substitutions per site, as long as the substitution number on each 
      branch was relatively small. The false-positive rate for detecting the selective 
      force was generally low. On the other hand, the true-positive rate for detecting 
      the selective force depended on the parameter values. Within the range of 
      parameter values used in the simulation, the true-positive rate increased as the 
      strength of the selective force and the total branch length (namely the total 
      number of synonymous substitutions per site) in the phylogenetic tree increased. 
      In particular, with the relative rate of nonsynonymous substitutions to 
      synonymous substitutions being 5.0, most of the positively selected codon sites 
      were correctly detected when the total branch length in the phylogenetic tree was 
      > or = 2.5. When this method was applied to the human leukocyte antigen (HLA) 
      gene, which included antigen recognition sites (ARSs), positive selection was 
      detected mainly on ARSs. This finding confirmed the effectiveness of the present 
      method with actual data. Moreover, two amino acid sites were newly identified as 
      positively selected in non-ARSs. The three-dimensional structure of the HLA 
      molecule indicated that these sites might be involved in antigen recognition. 
      Positively selected amino acid sites were also identified in the envelope protein 
      of human immunodeficiency virus and the influenza virus hemagglutinin protein. 
      This method may be helpful for predicting functions of amino acid sites in 
      proteins, especially in the present situation, in which sequence data are 
      accumulating at an enormous speed.
FAU - Suzuki, Y
AU  - Suzuki Y
AD  - Center for Information Biology, National Institute of Genetics, Mishima, Japan.
FAU - Gojobori, T
AU  - Gojobori T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Biol Evol
JT  - Molecular biology and evolution
JID - 8501455
RN  - 0 (Amino Acids)
RN  - 0 (Codon)
RN  - 0 (HIV Envelope Protein gp120)
RN  - 0 (HLA Antigens)
RN  - 0 (Hemagglutinin Glycoproteins, Influenza Virus)
SB  - IM
MH  - Amino Acid Substitution
MH  - Amino Acids/*genetics
MH  - Animals
MH  - Codon/genetics
MH  - Computer Simulation
MH  - Evolution, Molecular
MH  - HIV Envelope Protein gp120/genetics
MH  - HLA Antigens/chemistry/genetics
MH  - Hemagglutinin Glycoproteins, Influenza Virus/chemistry/genetics
MH  - Humans
MH  - Models, Genetic
MH  - Phylogeny
MH  - Protein Conformation
MH  - *Selection, Genetic
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - 10.1093/oxfordjournals.molbev.a026042 [doi]
PST - ppublish
SO  - Mol Biol Evol. 1999 Oct;16(10):1315-28. doi: 
      10.1093/oxfordjournals.molbev.a026042.