Distribution of fitness effects caused by single-nucleotide substitutions in bacteriophage f1.
Empirical knowledge of the fitness effects of mutations is important for understanding many evolutionary processes, yet this knowledge is often hampered by several sources of measurement error and bias. Most of these problems can be solved using site-directed mutagenesis to engineer single mutations, an approach particularly suited for viruses due to their small genomes. Here, we used this technique to measure the fitness effect of 100 single-nucleotide substitutions in the bacteriophage f1, a filamentous single-strand DNA virus. We found that approximately one-fifth of all mutations are lethal. Viable ones reduced fitness by 11% on average and were accurately described by a log-normal distribution. More than 90% of synonymous substitutions were selectively neutral, while those affecting intergenic regions reduced fitness by 14% on average. Mutations leading to amino acid substitutions had an overall mean deleterious effect of 37%, which increased to 45% for those changing the amino acid polarity. Interestingly, mutations affecting early steps of the infection cycle tended to be more deleterious than those affecting late steps. Finally, we observed at least two beneficial mutations. Our results confirm that high mutational sensitivity is a general property of viruses with small genomes, including RNA and single-strand DNA viruses infecting animals, plants, and bacteria.
Peris
Joan B
JB
Departament de Genètica, Institut Cavanilles de Biodiversitat i Biologia Evolutiva, Universitat de València, 46980 València, Spain.
Davis
Paulina
P
Cuevas
José M
JM
Nebot
Miguel R
MR
Sanjuán
Rafael
R
D019943:Amino Acid Substitution; D000818:Animals; D001435:Bacteriophages; D005075:Biological Evolution; D021901:DNA, Intergenic; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009711:Nucleotides
D021901:DNA, Intergenic; D009711:Nucleotides
Genetics. 2003 Apr;163(4):1519-26
12702694
Philos Trans R Soc Lond B Biol Sci. 2010 Jun 27;365(1548):1975-82
20478892
J Hered. 1993 Sep-Oct;84(5):339-44
8409355
Nat Rev Genet. 2007 Aug;8(8):610-8
17637733
Genetics. 1997 Apr;145(4):1171-99
9093868
EMBO Rep. 2006 Feb;7(2):168-73
16452927
Genetics. 2010 Jan;184(1):221-32
19858285
Evolution. 2003 Sep;57(9):1959-72
14575319
Genet Res. 2003 Aug;82(1):19-31
14621268
Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8396-401
15159545
Genetics. 1972 Oct;72(2):335-55
4630587
Genetics. 2005 Jul;170(3):989-99
15911582
Mol Syst Biol. 2006;2:2006.0008
16738554
Science. 1999 Sep 10;285(5434):1748-51
10481013
Genetics. 1977 Nov;87(3):547-56
200527
Evolution. 2004 Apr;58(4):692-701
15154545
PLoS Genet. 2009 Nov;5(11):e1000742
19956760
Genetics. 2001 Jan;157(1):53-61
11139491
Genetics. 2005 Aug;170(4):1449-57
15944361
J Virol. 2007 Dec;81(23):12979-84
17898073
Genetica. 1998;102-103(1-6):349-58
9720287
J Virol. 2007 Mar;81(6):2930-9
17202214
Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3823-7
9108062
Nature. 1996 Jun 20;381(6584):694-6
8649513
PLoS Biol. 2007 Apr;5(4):e94
17407380
Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):253-7
9419362
Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7160-4
1831267
Genetics. 1995 Sep;141(1):431-7
8536988
Genetics. 1998 Apr;148(4):1667-86
9560386
Genetics. 2004 Dec;168(4):1817-25
15611159
Genetics. 1996 Jun;143(2):829-37
8725231
Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):574-9
9892675