Investigating Protein-Coding Sequence Evolution with Probabilistic Codon Substitution Models

Anisimova, Maria; Kosiol, Carolin

doi:10.1093/molbev/msn232

Cited by 149 publications

(129 citation statements)

References 183 publications

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“…Although current site prediction methods arguably represent the most rigorous tools for analyzing selection in DNA sequences (2), it has been suggested that the statistical methods that underpin them have some limitations (40). Specifically, many of these methods require considerable sequence divergence (1) and have difficulty in identifying rare mutational events that are adaptive (40).…”

Section: Discussionmentioning

confidence: 99%

Tracking Viral Evolution during a Disease Outbreak: the Rapid and Complete Selective Sweep of a Circovirus in the Endangered Echo Parakeet

Kundu

Faulkes

Greenwood

et al. 2012

J Virol

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f Circoviruses are among the smallest and simplest of all viruses, but they are relatively poorly characterized. Here, we intensively sampled two sympatric parrot populations from Mauritius over a period of 11 years and screened for the circovirus Beak and feather disease virus (BFDV). During the sampling period, a severe outbreak of psittacine beak and feather disease, which is caused by BFDV, occurred in Echo parakeets. Consequently, this data set presents an ideal system for studying the evolution of a pathogen in a natural population and to understand the adaptive changes that cause outbreaks. Unexpectedly, we discovered that the outbreak was most likely caused by changes in functionally important regions of the normally conserved replicationassociated protein gene and not the immunogenic capsid. Moreover, these mutations were completely fixed in the Echo parakeet host population very shortly after the outbreak. Several capsid alleles were linked to the replication-associated protein outbreak allele, suggesting that whereas the key changes occurred in the latter, the scope of the outbreak and the selective sweep may have been influenced by positive selection in the capsid. We found evidence for viral transmission between the two host populations though evidence for the invasive species as the source of the outbreak was equivocal. Finally, the high evolutionary rate that we estimated shows how rapidly new variation can arise in BFDV and is consistent with recent results from other small singlestranded DNA viruses.

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Section: Discussionmentioning

confidence: 99%

Tracking Viral Evolution during a Disease Outbreak: the Rapid and Complete Selective Sweep of a Circovirus in the Endangered Echo Parakeet

Kundu

Faulkes

Greenwood

et al. 2012

J Virol

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“…We estimated the per-site diversity level as the proportion of non-HXB2 amino acids, assuming that each amino acid residue is independent. Although this is probably an overestimate of the amount of diversity, it is sufficient for the purposes of our analysis in the absence of a phylogeny (4,13). For each DRM site, we ranked the diversity level against all other codons and assessed a median mutation rank for all DRM sites combined.…”

Section: Methodsmentioning

confidence: 99%

Detection of Minority Resistance during Early HIV-1 Infection: Natural Variation and Spurious Detection rather than Transmission and Evolution of Multiple Viral Variants

Gianella

Delport

Pacold

et al. 2011

J Virol

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Reports of a high frequency of the transmission of minority viral populations with drug-resistant mutations (DRM) are inconsistent with evidence that HIV-1 infections usually arise from mono-or oligoclonal transmission. We performed ultradeep sequencing (UDS) of partial HIV-1 gag, pol, and env genes from 32 recently infected individuals. We then evaluated overall and per-site diversity levels, selective pressure, sequence reproducibility, and presence of DRM and accessory mutations (AM). To differentiate biologically meaningful mutations from those caused by methodological errors, we obtained multinomial confidence intervals (CI) for the proportion of DRM at each site and fitted a binomial mixture model to determine background error rates for each sample. We then examined the association between detected minority DRM and the virologic failure of first-line antiretroviral therapy (ART). Similar to other studies, we observed increased detection of DRM at low frequencies (average, 0.56%; 95% CI, 0.43 to 0.69; expected UDS error, 0.21 ؎ 0.08% mutations/site). For 8 duplicate runs, there was variability in the proportions of minority DRM. There was no indication of increased diversity or selection at DRM sites compared to other sites and no association between minority DRM and AM. There was no correlation between detected minority DRM and clinical failure of first-line ART. It is unlikely that minority viral variants harboring DRM are transmitted and maintained in the recipient host. The majority of low-frequency DRM detected using UDS are likely errors inherent to UDS methodology or a consequence of error-prone HIV-1 replication.Using standard population-based genotypic assays of HIV from individuals not yet treated with antiretroviral drugs, several studies (43,64,69,76) have estimated the rate of transmitted drug resistance to be between 8 and 27% in countries with the highest rates of antiretroviral therapy (ART) use. In resource-limited settings, in which the introduction of ART has been more recent, the estimated frequency of transmitted drug resistance mutations (DRM) is substantially lower (41). It appears, however, to be increasing in these settings as well (2,14,51). Using more-sensitive genotypic assays, different research groups (15,30,32,37,48,58,65) have reported higher proportions of transmitted DRM in ART-naive individuals. The clinical importance of these low-level DRM remains unclear, as they have been associated with clinical consequences in some (21,24,32,36,37,40,46,54,55,63,66,71) but not all (30, 47, 58) studies.Highly sensitive assays for detecting low-frequency DRM include point mutation assays and high-resolution sequencing techniques. Point mutation assays, such as allele-specific PCR, can detect DRM at frequencies as low as 0.01% of the sampled viral population (31,45,53,54), but they do not provide information about the sequence context surrounding a given DRM and may be prone to false positives at the lower level of detection (22). High-resolution sequencing techniques, such as single ge...

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“…The selective pressure operating on the core eudicot PDATs was estimated using the ratio (v) of the nonsynonymous substitution rate versus the K S as an indicator (Yang and Bielawski, 2000;Anisimova and Kosiol, 2009): 0 , v , 1 corresponds to purifying selection, v = 1 indicates neutral selection, and v . 1 suggests positive selection.…”

Section: Gene Expansion Pattern and Selective Pressure Analysismentioning

confidence: 99%

Genome-Wide Analysis ofPHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE(PDAT) Genes in Plants Reveals the Eudicot-WidePDATGene Expansion and Altered Selective Pressures Acting on the Core EudicotPDATParalogs

2015

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PHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE (PDAT) is an enzyme that catalyzes the transfer of a fatty acyl moiety from the sn-2 position of a phospholipid to the sn-3-position of sn-1,2-diacylglyerol, thus forming triacylglycerol and a lysophospholipid. Although the importance of PDAT in triacylglycerol biosynthesis has been illustrated in some previous studies, the evolutionary relationship of plant PDATs has not been studied in detail. In this study, we investigated the evolutionary relationship of the PDAT gene family across the green plants using a comparative phylogenetic framework. We found that the PDAT candidate genes are present in all examined green plants, including algae, lowland plants (a moss and a lycophyte), monocots, and eudicots. Phylogenetic analysis revealed the evolutionary division of the PDAT gene family into seven major clades. The separation is supported by the conservation and variation in the gene structure, protein properties, motif patterns, and/or selection constraints. We further demonstrated that there is a eudicot-wide PDAT gene expansion, which appears to have been mainly caused by the eudicot-shared ancient gene duplication and subsequent species-specific segmental duplications. In addition, selection pressure analyses showed that different selection constraints have acted on three core eudicot clades, which might enable paleoduplicated PDAT paralogs to either become nonfunctionalized or develop divergent expression patterns during evolution. Overall, our study provides important insights into the evolution of the plant PDAT gene family and explores the evolutionary mechanism underlying the functional diversification among the core eudicot PDAT paralogs.

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Investigating Protein-Coding Sequence Evolution with Probabilistic Codon Substitution Models

Cited by 149 publications

References 183 publications

Tracking Viral Evolution during a Disease Outbreak: the Rapid and Complete Selective Sweep of a Circovirus in the Endangered Echo Parakeet

Tracking Viral Evolution during a Disease Outbreak: the Rapid and Complete Selective Sweep of a Circovirus in the Endangered Echo Parakeet

Detection of Minority Resistance during Early HIV-1 Infection: Natural Variation and Spurious Detection rather than Transmission and Evolution of Multiple Viral Variants

Genome-Wide Analysis ofPHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE(PDAT) Genes in Plants Reveals the Eudicot-WidePDATGene Expansion and Altered Selective Pressures Acting on the Core EudicotPDATParalogs

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