Molecular evolution of GYPC: evidence for recent structural innovation and positive selection in humans.
GYPC encodes two erythrocyte surface sialoglycoproteins in humans, glycophorin C and glycophorin D (GPC and GPD), via initiation of translation at two start codons on a single transcript. The malaria-causing parasite Plasmodium falciparum uses GPC as a means of invasion into the human red blood cell. Here, we examine the molecular evolution of GYPC among the Hominoidea (Greater and Lesser Apes) and also the pattern of polymorphism at the locus in a global human sample. We find an excess of nonsynonymous divergence among species that appears to be caused solely by accelerated evolution of GYPC in the human lineage. Moreover, we find that the ability of GYPC to encode both GPC and GPD is a uniquely human trait, caused by the evolution of the GPC start codon in the human lineage. The pattern of polymorphism among humans is consistent with a hitchhiking event at the locus, suggesting that positive natural selection affected GYPC in the relatively recent past. Because GPC is exploited by P. falciparum for invasion of the red blood cell, we hypothesize that selection for evasion of P. falciparum has caused accelerated evolution of GYPC in humans (relative to other primates) and that this positive selection has continued to act in the recent evolution of our species. These data suggest that malaria has played a powerful role in shaping molecules on the surface of the human red blood cell. In addition, our examination of GYPC reveals a novel mechanism of protein evolution: co-option of untranslated region (UTR) sequence following the formation of a new start codon. In the case of human GYPC, the ancestral protein (GPD) continues to be produced through leaky translation. Because leaky translation is a widespread phenomenon among genes and organisms, we suggest that co-option of UTR sequence may be an important source of protein innovation.
Wilder
Jason A
JA
Department of Biological Sciences, Northern Arizona University, USA. jason.wilder@nau.edu
Hewett
Elizabeth K
EK
Gansner
Meredith E
ME
D001483:Base Sequence; D003062:Codon / Q000235:genetics; D019143:Evolution, Molecular; D006021:Glycophorins / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010442:Peptide Chain Initiation, Translational / Q000235:genetics; D011110:Polymorphism, Genetic; D012641:Selection, Genetic / Q000235:genetics*
D003062:Codon; D006021:Glycophorins
Proc Natl Acad Sci U S A. 1979 Oct;76(10):5269-73
291943
Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2358-62
16461900
Nature. 1991 Jun 20;351(6328):652-4
1904993
Trends Genet. 2002 Nov;18(11):559-63
12414185
Genetics. 2002 Mar;160(3):1179-89
11901132
Biochem J. 1988 Mar 1;250(2):407-14
2833242
Genetics. 2000 May;155(1):431-49
10790415
Annu Rev Genet. 2005;39:197-218
16285858
J Exp Med. 2002 Dec 2;196(11):1523-8
12461087
Vox Sang. 1972 Jan;22(1):73-84
5011657
Genetics. 2006 Nov;174(3):1431-9
16951063
Gene. 2002 Oct 16;299(1-2):1-34
12459250
J Biol Chem. 1993 Jan 25;268(3):2260-7
8420995
Genetics. 1993 Mar;133(3):693-709
8454210
Mol Cell Biochem. 1973 Dec 15;2(2):197-218
4272551
Mol Biol Evol. 2002 Mar;19(3):223-9
11861881
Theor Popul Biol. 1975 Apr;7(2):256-76
1145509
Immunol Cell Biol. 1994 Feb;72(1):23-7
8157284
Genetics. 2000 Jul;155(3):1405-13
10880498
Methods Enzymol. 1974;31:168-72
4278921
Genetics. 2004 Oct;168(2):1041-51
15514074
Am J Hematol. 2004 Jan;75(1):1-5
14695625
Mol Biol Evol. 2003 Jan;20(1):18-20
12519901
Blood. 2001 Dec 1;98(12):3489-91
11719395
Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12819-24
16126901
Bioinformatics. 2003 Dec 12;19(18):2496-7
14668244
Nat Med. 2003 Jan;9(1):87-92
12469115
Mol Biol Evol. 2007 Aug;24(8):1586-91
17483113
Trends Parasitol. 2001 Jun;17(6):297-9
11378038
Trends Parasitol. 2008 Nov;24(11):517-24
18805736
Mol Biol Evol. 2003 Nov;20(11):1795-804
12949139
Gene. 1995 Jul 4;159(2):225-30
7622054
Mol Biol Evol. 2005 Apr;22(4):1107-18
15689528
Genetics. 2002 Feb;160(2):765-77
11861577
Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2518-23
14983041
Br J Haematol. 1995 Mar;89(3):440-8
7734343
Blood. 1996 Sep 15;88(6):2364-5
8822964
Mol Biol Evol. 2005 Dec;22(12):2472-9
16107592
Genetics. 2003 Aug;164(4):1495-509
12930755
Infect Immun. 2009 Apr;77(4):1689-99
19204093
Genetics. 2000 Jul;155(3):1415-27
10880499
Genetics. 1989 Nov;123(3):585-95
2513255
Int J Parasitol. 2004 Dec;34(13-14):1413-29
15582519