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DutchyA search of the influenza virus genome database reveals anomalies associated with a nonnegligible number of submitted sequences. There are many pairs of viral segments that are very close to each other in nucleotide sequence but relatively far apart in reported time of isolation, resulting in an abnormally low evolutionary rate. Also, some sequences show clear evidence of apparent homologous recombination, a process normally assumed to be extremely rare or nonexistent in this virus. These findings may point to surprising new biology but are perhaps more readily explained by stock contamination or other errors in the sequencing laboratories.
Michael Krasnitz,* Arnold J. Levine, and Raul Rabadan*
Institute for Advanced Study, Einstein Dr., Princeton, New Jersey 08540
Received 15 January 2008/ Accepted 6 June 2008
Discussing "frozen in time" sequences:
Each of the anomalous sequences is so close to some other sequence in the database compared to their distance in time that any model would rule out the possibility of a random fluctuation; there is clearly something extraordinary about these sequences.
Appendix 1: Influenza sequences “frozen in time”
A/Hickox/1940(H1N1)
A/FortWorth/50(H1N1)
A/Alma Ata/1417/84(H1N1)
A/Neimenggu/63/1997(H1N1)
A/Nanjing/49/77(H3N2)
A/HongKong/498/97(H3N2)
A/Victoria/1968(H3N2)
A/ruddy turnstone/NJ/65/1985(H7N3)
A/chicken/Brescia/1902(H7N7)
A/fowl/Dobson/1927(H7N7)
A/wedge-tailed shearwater/Western Australia/2576/1979(H15N9)
A/ruddy turnstone/NJ/47/1985(H4N6)
A/duck/Taiwan/0526/72(H1N1)
A/duck/Zhejiang/11/2000(H5N1)
A/chicken/Hebei/1/2002(H7N2)
A/tree sparrow/Henan/1/2004(H5N1)
A/tree sparrow/Henan/2/2004(H5N1)
A/tree sparrow/Henan/3/2004(H5N1)
A/tree sparrow/Henan/4/2004(H5N1)
A/chicken/Hubei/wk/1997(H5N1)
A/duck/Vietnam/8/05(H5N1)
A/chicken/Henan/wu/2004(H5N1)
A/wild duck/Guangdong/314/2004(H5N1)
A/mallard/Guangxi/wt/2004(H5N1)
A/chicken/Heilongjiang/35/00(H9N2)
A/goose/Vietnam/3/05(H5N1)
A/grey teal/Australia/2/1979(H4N4)
A/turkey/Canada/63(H9N2)
A/turkey/England/N28/73(H6N2)
A/mallard/Astrakhan/263/1982(H14N5)
A/shearwater/Australia/1/1972(H6N5)
A/shearwater/Australia//1/1973(H6N5)
A/duck/Minnesota/3/1992(H5N2)
A/duck/Mongolia/54/2001(H5N2)
A/slaty-backed gull/Shandong/38/04(H5N1)
A/chicken/Jilin/9/2004(H5N1)
A/duck/Xuzhou/07/2003(H9N2)
A/bird/Guangxi/A1/2006
A/mallard/Alberta/245/2003(H11N9)
A/chicken/Hebei/718/2001(H5N1)
A/mallard duck/ALB/76/1985(H6N3)
A/chicken/Taiwan/4801/90(H6N5)
A/duck/Hubei/W1/2004(H9N2)
A/duck/Ontario/05/00(H3N2)
A/swine/Ontario/48235/04(H1N2)
A/swine/Ontario/55383/04(H1N2)
A/swine/Alberta/56626/03(H1N1)
A/swine/Alberta/53518/03(H1N1)
A/swine/St-Hyacinthe/148/1990(H1N1)
A/swine/Ange-Gardien/150/1990(H3N2)
A/swine/Heilongjiang/74/2000(H3N2)
A/swine/Ontario/11112/04(H1N1)
A/swine/Guangdong/4/2005(H3N2)
A/swine/England/191973/92(H1N7)
A/swine/Jamesburg/1942(H1N1)
A/swine/41/1949(H1N1)
A/swine/Iowa/1946(H1N1)
A/swine/Inner Mongolia/547/2001(H3N2)
A/whale/P.O./19/1976(H1N3)
Appendix 2: Sequences showing evidence of homologous recombination
A/laughing gull/DE/94/2000(H12N4)
A/shorebird/DE/236/2003(H11N9)
A/tree sparrow/Henan/1/2004(H5N1)
A/tree sparrow/Henan/2/2004
A/tree sparrow/Henan/3/2004
A/tree sparrow/Henan/4/2004
A/chicken/Jilin/ha/2003(H5N1)
A/chicken/Hebei/718/2001(H5N1)
A/chicken/Jilin/9/2004(H5N1)
A/chicken/Hebei/wi/1997(H5N1)
A/grey teal/Australia/1/1979(H6N1)
A/duck/Taiwan/0526/1972(H6N1)
A/chicken/Taiwan/G2/87(H6N1)
A/chicken/Taiwan/G23/87(H6N1)
A/chicken/Jilin/hk/2004(H5N1)
A/chicken/Jilin/hd/2002(H5N1)
A/goose/Jilin/hb/2003(H5N1)
A/chicken/Jilin/xw/2003(H5N1)
A/chicken/Jilin//xv/2002(H5N1)
A/duck/Hubei/wq/2003(H5N1)
A/goose/Guangdong/xb/2001(H5N1)
A/chicken/Taiwan/PF2/02(H6N1)
A/chicken/Taiwan/PF3/02(H6N1)
A/Sck/HK/Yu100/2002(H5N1)
A/duck/Vietnam/8/05(H5N1)
A/chicken/Hubei/wk/1997(H5N1)
A/chicken/Hubei/wj/1997(H5N1)
A/chicken/Hebei/108/02(H5N1)
A/chicken/Henan/2/98(H9N2)
A/chicken/Gansu/1/99(H9N2)
A/chicken/Tianjing/1/96(H9N2)
A/duck/Nanjing/2/97(H9N2)
A/duck/Vietnam/1/2005(H5N1)
A/swine/Indiana/P12439/00(H1N2)
A/swine/Korea/CN22/2006(H3N1)
A/swine/Ontario/53518/03(H1N1)
A/swine/Ontario/57561/03(H1N1)
A/swine/Ontario/11112/04(H1N1)
A/swine/Ontario/48235/04(H1N2)
A/swine/Ontario/55383/04(H1N2)
A/swine/St-Hyacinthe/106/1991(H1)
A/Swine/Wisconsin/458/98(H1N1)
A/Swine/Wisconsin/464/98(H1N1)
A/swine/British Columbia/28103/2005(H3N2)
A/Swine/Iowa/930/01(H1N2)
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