title: Confounders of mutation-rate estimators: selection and phenotypic lag in Thermus thermophilus.
abstract: In a recent description of the rate and character of spontaneous mutation in the hyperthermophilic bacterium Thermus thermophilus, the mutation rate was observed to be substantially lower than seen in several mesophiles. Subsequently, a report appeared indicating that this bacterium maintains an average of about 4.5 genomes per cell. This number of genomes might result in a segregation lag for the expression of a recessive mutation and might therefore lead to an underestimate of the rate of mutation. Here we describe some kinds of problems that may arise when estimating mutation rates and outline ways to adjust the rates accordingly. The emphasis is mainly on differential rates of growth of mutants versus their parents and on various kinds of phenotypic lag. We then apply these methods to the T. thermophilus data and conclude that there is as yet no reliable impact on a previously described rate.
authors.affiliation: Biostatistics Branch, National Institute of Environmental Health Sciences (NIH), Research Triangle Park, NC 27709, USA.
authors.forename: Grace E
authors.initials: GE
authors.lastname: Kissling
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Grogan
authors.forename: John W
authors.initials: JW
authors.lastname: Drake
mesh_terms: D015964:Gene Expression Regulation, Bacterial; D008962:Models, Theoretical; D009154:Mutation / Q000502:physiology; D059645:Mutation Rate; D010641:Phenotype; D012641:Selection, Genetic / Q000502:physiology*; D016963:Thermus thermophilus / Q000235:genetics* / Q000254:growth & development*
keywords: Differential growth rates; Fluctuation test; Mutation rate; Phenotypic lag
references.citation: Genetics. 2008 Jan;178(1):67-82
references.pmid: 18202359
references.citation: Methods Enzymol. 2006;409:195-213
references.pmid: 16793403
references.citation: Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7928-33
references.pmid: 11427720
references.citation: Genetics. 2008 Sep;180(1):17-25
references.pmid: 18723895
references.citation: Cold Spring Harb Symp Quant Biol. 1951;16:463-70
references.pmid: 14942756
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D646-52
references.pmid: 22080555
references.citation: PLoS Genet. 2009 Jun;5(6):e1000520
references.pmid: 19543367
references.citation: J Bacteriol. 1994 Jul;176(13):3911-9
references.pmid: 8021173
references.citation: Genetics. 1992 Dec;132(4):869-78
references.pmid: 1334019
references.citation: Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7160-4
references.pmid: 1831267
references.citation: Nature. 1993 Sep 16;365(6443):274-6
references.pmid: 8371783
references.citation: J Virol. 1973 Jan;11(1):35-40
references.pmid: 4567687
references.citation: Genetics. 2007 May;176(1):697-702
references.pmid: 17194771
references.citation: Genetics. 2004 Jul;167(3):1507-12
references.pmid: 15280258
references.citation: Genetics. 1948 Sep;33(5):447-76
references.pmid: 17247291
references.citation: J Bacteriol. 2010 Oct;192(20):5499-505
references.pmid: 20729360
references.citation: Genetics. 1943 Nov;28(6):491-511
references.pmid: 17247100