Reappraisal of the historical selective pressures for the CCR5-Delta32 mutation.
HIV strains are unable to enter macrophages that carry the CCR5-Delta32 deletion; the average frequency of this allele is 10% in European populations. A mathematical model based on the changing demography of Europe from 1000 to 1800 AD demonstrates how plague epidemics, 1347 to 1670, could have provided the selection pressure that raised the frequency of the mutation to the level seen today. It is suggested that the original single mutation appeared over 2500 years ago and that persistent epidemics of a haemorrhagic fever that struck at the early classical civilisations served to force up the frequency to about 5x10(-5) at the time of the Black Death in 1347.
Duncan
S R
SR
Department of Engineering Science, University of Oxford, Parks Road, Oxford, UK.
Scott
S
S
Duncan
C J
CJ
D004196:Disease Outbreaks / Q000266:history; D015658:HIV Infections / Q000276:immunology; D006482:Hemorrhagic Fevers, Viral / Q000453:epidemiology / Q000235:genetics / Q000266:history; D049668:History, 15th Century; D049669:History, 16th Century; D049670:History, 17th Century; D049691:History, Medieval; D007113:Immunity, Innate; D008957:Models, Genetic; D010930:Plague / Q000453:epidemiology / Q000235:genetics / Q000266:history; D019713:Receptors, CCR5 / Q000235:genetics*; D012641:Selection, Genetic; D017384:Sequence Deletion
D019713:Receptors, CCR5
Science. 1999 Dec 3;286(5446):1968-71
10583963
Am J Hum Genet. 1998 Jun;62(6):1507-15
9585595
Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):183-8
12518064
Med Hist. 2003 Oct;47(4):413-50
14619634
Nature. 2004 Feb 12;427(6975):606
14961112
Nature. 1996 Jun 20;381(6584):661-6
8649511
Cell. 1996 Jun 28;85(7):1135-48
8674119
Cell. 1996 Jun 28;85(7):1149-58
8674120
Science. 1996 Jun 28;272(5270):1955-8
8658171
Nature. 1996 Aug 22;382(6593):722-5
8751444
Science. 1996 Sep 27;273(5283):1856-62
8791590
Nat Med. 1996 Nov;2(11):1240-3
8898752
Nat Med. 1997 Mar;3(3):338-40
9055864
Trop Med Int Health. 1997 Jun;2(6):603-6
9236828
Hum Mol Genet. 1998 Mar;7(3):399-406
9466996
J Acquir Immune Defic Syndr. 2001 Aug 15;27(5):472-81
11511825