Maximum Likelihood Estimation of Ancestral Codon Usage Bias Parameters in Drosophila

Nielsen, Rasmus; DuMont, Vanessa L. Bauer; Hubisz, Melissa J.; Aquadro, Charles F.

doi:10.1093/molbev/msl146

Cited by 77 publications

(96 citation statements)

References 35 publications

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“…For this reason, we were unable to obtain a 95% confidence interval under L 1 . Furthermore, consistent with many previous reports (Petrov and Hartl 1999;McVean and Vieira 2001;Nielsen et al 2007;Keightley et al 2009), the mutational process is not symmetric, but is biased toward preferred-to-unpreferred changes [L 0 …”

Section: Initial Analysissupporting

confidence: 89%

“…However, a number of studies have also found that selection on synonymous sites may have been substantially reduced in the D. melanogaster lineage (Akashi 1995(Akashi , 1996Vieira 1999, 2001;Nielsen et al 2007). A common feature of these studies is that they used between-species divergence data and drew conclusions on the basis of the observation that D. melanogaster synonymous sites have fixed significantly more unpreferred alleles than preferred variants (the rates of fixation should be equal at equilibrium).…”

Section: Discussionmentioning

confidence: 99%

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Estimating Selection Intensity on Synonymous Codon Usage in a Nonequilibrium Population

2009

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Codon usage bias is the nonrandom use of synonymous codons for the same amino acid. Most population genetic models of codon usage evolution assume that the population is at mutation-selection-drift equilibrium. Natural populations, however, frequently deviate from equilibrium, often because of recent demographic changes. Here, we construct a matrix model that includes the effects of a recent change in population size on estimates of selection on preferred vs. unpreferred codons. Our results suggest that patterns of synonymous polymorphisms affecting codon usage can be quite erratic after such a change; statistical methods that fail to take demographic effects into account can then give incorrect estimates of important parameters. We propose a new method that can accurately estimate both demographic and codon usage parameters. The method also provides a simple way of testing for the effects of covariates such as gene length and level of gene expression on the intensity of selection, which we apply to a large Drosophila melanogaster polymorphism data set. Our analyses of twofold degenerate codons reveal that (i) selection acts in favor of preferred codons, (ii) there is mutational bias in favor of unpreferred codons, (iii) shorter genes and genes with higher expression levels are under stronger selection, and (iv) there is little evidence for a recent change in population size in the Zimbabwe population of D. melanogaster. CODONS specifying the same amino acid are called synonymous codons. These are often used nonrandomly, with some codons appearing more frequently than others. This biased usage of synonymous codons has been found in many organisms such as Drosophila, yeast, and bacteria (Ikemura 1985;Duret and Mouchiroud 1999;Hershberg and Petrov 2008). Conventionally, synonymous codons for a given amino acid are divided into two classes: preferred and unpreferred codons (Ikemura 1985;Akashi 1994;Duret and Mouchiroud 1999). Several observations indicate that codon usage is affected by natural selection. First, in species with codon usage bias, preferred codons generally correspond to the most abundant tRNA species (Ikemura 1981). Second, highly expressed genes usually have higher codon usage bias than genes with low expression (Sharp and Li 1986;Duret and Mouchiroud 1999;Hey and Kliman 2002). Third, the synonymous substitution rate of a gene has been shown to be negatively correlated with its degree of codon usage bias (Sharp and Li 1986;Bierne and Eyre-Walker 2006). The most commonly cited explanations of the apparent fitness differences between preferred and unpreferred codons are selection for translation efficiency, translational accuracy, and mRNA stability (Ikemura 1985;Eyre-Walker and Bulmer 1993;Akashi 1994;Drummond et al. 2005). Recently, it has been proposed that exon splicing also affects codon usage bias (Warnecke and Hurst 2007).From a population genetics perspective, the extent of codon usage bias is ultimately a product of the joint effects of mutation, selection, genetic drift, recombinati...

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Section: Initial Analysissupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Estimating Selection Intensity on Synonymous Codon Usage in a Nonequilibrium Population

2009

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“…We found evidence for a lineagespecific genomic reduction in codon bias in D. melanogaster (Fig. 5), as has been suggested previously [113][114][115][116][117][118][119] . In addition, maximum-likelihood estimation of the strength of selection on synonymous sites in 8,510 melanogaster group single-copy orthologues revealed a marked reduction in the number of genes under selection for increased codon bias in D. melanogaster relative to its sister species D. sechellia 120 .…”

Section: Articlessupporting

confidence: 87%

Evolution of genes and genomes on the Drosophila phylogeny

Clark¹,

Eisen²,

Smith³

et al. 2007

Nature

1,818

1,041

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Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

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“…These patterns are expected with a selective sweep model, but not under a simple model of selection on synonymous sites in which selection coefficients on such mutations are predicted to be on the order of the reciprocal of the effective population size (e.g., Akashi and Schaeffer 1997;Comeron and Guthrie 2005;Nielsen et al 2007). With our current data, we cannot exclude that a change in synonymous site selective pressure and/or a change in mutation bias along the D. melanogaster lineage (e.g., Nielsen et al 2007), in association with a linked selective sweep, has led to our significant MK test results. Regardless, our results illustrate the potential importance of sample size in inference of fixed vs. polymorphic states and in assessing differences in frequency spectra between different types of mutations.…”

Section: Discussionmentioning

confidence: 85%

Patterns of Sequence Variability and Divergence at the diminutive Gene Region of Drosophila melanogaster: Complex Patterns Suggest an Ancestral Selective Sweep

et al. 2007

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To identify putatively swept regions of the Drosophila melanogaster genome, we performed a microsatellite screen spanning a 260-kb region of the X chromosome in populations from Zimbabwe, Ecuador, the United States, and China. Among the regions identified by this screen as showing a complex pattern of reduced heterozygosity and a skewed frequency spectrum was the gene diminutive (dm). To investigate the microsatellite findings, nucleotide sequence polymorphism data were generated in populations from both China and Zimbabwe spanning a 25-kb region and encompassing dm. Analysis of the sequence data reveals strongly reduced nucleotide variation across the entire gene region in both the non-African and the African populations, an extended haplotype pattern, and structured linkage disequilibrium, as well as a rejection of neutrality in favor of selection using a composite likelihood-ratio test. Additionally, unusual patterns of synonymous site evolution were observed at the second exon of this locus. On the basis of simulation studies as well as recently proposed methods for distinguishing between selection and nonequilibrium demography, we find that this ''footprint'' is best explained by a selective sweep in the ancestral population, the signal of which has been somewhat blurred via founder effects in the non-African samples.

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Maximum Likelihood Estimation of Ancestral Codon Usage Bias Parameters in Drosophila

Cited by 77 publications

References 35 publications

Estimating Selection Intensity on Synonymous Codon Usage in a Nonequilibrium Population

Estimating Selection Intensity on Synonymous Codon Usage in a Nonequilibrium Population

Evolution of genes and genomes on the Drosophila phylogeny

Patterns of Sequence Variability and Divergence at the diminutive Gene Region of Drosophila melanogaster: Complex Patterns Suggest an Ancestral Selective Sweep

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