The Fitness Effects of Synonymous Mutations in DNA and RNA Viruses

被引：89

作者：

Cuevas, Jose M. ^{[1
]}

Domingo-Calap, Pilar ^{[1
]}

Sanjuan, Rafael ^{[1
,2
,3
]}

机构：

[1] Univ Valencia, Inst Cavanilles Biodiversitat & Biol Evolutiva, Valencia, Spain

[2] Univ Valencia, Dept Genet, Valencia, Spain

[3] CSISP, Unidad Mixta Invest Genom & Salud, Valencia, Spain

来源：

MOLECULAR BIOLOGY AND EVOLUTION | 2012年 / 29卷 / 01期

关键词：

synonymous substitutions; nonsynonymous substitutions; silent substitutions; RNA structure; codon usage bias; RNA virus; DNA virus; selection; evolution; site-directed mutagenesis; mutational robustness; mutational fitness effects; SINGLE-NUCLEOTIDE SUBSTITUTIONS; HEPATITIS-C VIRUS; TRANSLATIONAL CONTROL; SECONDARY STRUCTURES; GENE-EXPRESSION; SELECTION; EVOLUTION; GENOME; STABILITY; PROTEIN;

D O I：

10.1093/molbev/msr179

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Despite being silent with respect to protein sequence, synonymous nucleotide substitutions can be targeted by natural selection directly at the DNA or RNA level. However, there has been no systematic assessment of how frequent this type of selection is. Here, we have constructed 53 single random synonymous substitution mutants of the bacteriophages Q beta and Phi X174 by site-directed mutagenesis and assayed their fitness. Analysis of this mutant collection and of previous studies undertaken with a variety of single-stranded (ss) viruses demonstrates that selection at synonymous sites is stronger in RNA viruses than in DNA viruses. We estimate that this type of selection contributes approximately 18% of the overall mutational fitness effects in ssRNA viruses under our assay conditions and that random synonymous substitutions have a 5% chance of being lethal to the virus, whereas in ssDNA viruses, these figures drop to 1.4% and 0%, respectively. In contrast, the effects of nonsynonymous substitutions appear to be similar in ssRNA and ssDNA viruses.

引用

页码：17 / 20

页数：4

共 30 条

[1]

Bull JJ, 1997, GENETICS, V147, P1497

[2] Distribution of fitness and virulence effects caused by single-nucleotide substitutions in tobacco etch virus [J].

Carrasco, Purificacion ;

de la Iglesia, Francisca ;

Elena, Santiago F. .

JOURNAL OF VIROLOGY, 2007, 81 (23) :12979-12984

[3] Evidence for selection on synonymous mutations affecting stability of mRNA secondary structure in mammals [J].

Chamary, JV ;

Hurst, LD .

GENOME BIOLOGY, 2005, 6 (09)

[4]

Cuevas JM, 2002, GENETICS, V162, P533

[5] HIGH-FREQUENCY OF SINGLE-BASE TRANSITIONS AND EXTREME FREQUENCY OF PRECISE MULTIPLE-BASE REVERSION MUTATIONS IN POLIOVIRUS [J].

DELATORRE, JC ;

GIACHETTI, C ;

SEMLER, BL ;

HOLLAND, JJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (07) :2531-2535

[6] The Fitness Effects of Random Mutations in Single-Stranded DNA and RNA Bacteriophages [J].

Domingo-Calap, Pilar ;

Cuevas, Jose M. ;

Sanjuan, Rafael .

PLOS GENETICS, 2009, 5 (11)

[7]

GROENEVELD H, 1995, RNA, V1, P79

[8] RNA sensors: novel regulators of gene expression [J].

Kaempfer, R .

EMBO REPORTS, 2003, 4 (11) :1043-1047

[9] Rapid evolution of translational control mechanisms in RNA genomes [J].

Klovins, J ;

Tsareva, NA ;

deSmith, MH ;

Berzins, V ;

vanDuin, J .

JOURNAL OF MOLECULAR BIOLOGY, 1997, 265 (04) :372-384

[10] A long-range interaction in Qβ RNA that bridges the thousand nucleotides between the M-site and the 3′ end is required for replication [J].

Klovins, J ;

Berzins, V ;

Van Duin, J .

RNA, 1998, 4 (08) :948-957

← 1 2 3 →