Sampling and Processing HIV Molecular Sequences: A Computational Evolutionary Biologist’s Perspective

Rodrigo, Allen G.; Hanley, Edward W.; Goracke, Paul C.; Learn, Gerald H.

doi:10.1007/0-306-46900-6_1

Cited by 8 publications

(7 citation statements)

References 18 publications

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“…Phylogenetic tree for relationship of subgroup Ia COL protein sequences was inferred using the Neighbor-Joining method in MEGA5 with bootstrap values from 10,000 replicates ( Saitou and Nei 1987 ; Tamura et al 2007 ). Substitution rates were calculated from a codon alignment of the respective CDS followed by calculation of substitution rates corrected by Jukes–Cantor method using SNAP v1.1.1 ( Rodrigo and Learn 2001 , Chapter 4, p. 55–72). CO promoter and COL locus alignments were performed using LAGAN algorithm on mVISTA ( Mayor et al 2000 ; Brudno et al 2003 ).…”

Section: Methodsmentioning

confidence: 99%

Evolution ofCONSTANSRegulation and Function after Gene Duplication Produced a Photoperiodic Flowering Switch in the Brassicaceae

et al. 2015

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Environmental control of flowering allows plant reproduction to occur under optimal conditions and facilitates adaptation to different locations. At high latitude, flowering of many plants is controlled by seasonal changes in day length. The photoperiodic flowering pathway confers this response in the Brassicaceae, which colonized temperate latitudes after divergence from the Cleomaceae, their subtropical sister family. The CONSTANS (CO) transcription factor of Arabidopsis thaliana, a member of the Brassicaceae, is central to the photoperiodic flowering response and shows characteristic patterns of transcription required for day-length sensing. CO is believed to be widely conserved among flowering plants; however, we show that it arose after gene duplication at the root of the Brassicaceae followed by divergence of transcriptional regulation and protein function. CO has two close homologs, CONSTANS-LIKE1 (COL1) and COL2, which are related to CO by tandem duplication and whole-genome duplication, respectively. The single CO homolog present in the Cleomaceae shows transcriptional and functional features similar to those of COL1 and COL2, suggesting that these were ancestral. We detect cis-regulatory and codon changes characteristic of CO and use transgenic assays to demonstrate their significance in the day-length-dependent activation of the CO target gene FLOWERING LOCUS T. Thus, the function of CO as a potent photoperiodic flowering switch evolved in the Brassicaceae after gene duplication. The origin of CO may have contributed to the range expansion of the Brassicaceae and suggests that in other families CO genes involved in photoperiodic flowering arose by convergent evolution.

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Section: Methodsmentioning

confidence: 99%

Evolution ofCONSTANSRegulation and Function after Gene Duplication Produced a Photoperiodic Flowering Switch in the Brassicaceae

et al. 2015

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“…Samples that did not amplify with the forward PR primers PRL and PRC were amplified using either pol-forward outer and pol-forward inner (19), PRF1 (5Ј-GAGCCAAGTAACAAATTCAGC-3Ј) and PRF2 (5Ј-CACCAGAAGAGAGCTTCAGGT-3Ј), or PRA (5Ј-CCTAGG AAAAAGGGCTGTTGGAAATGTGG-3Ј) and PRB (5Ј-ACTGAGAGACAGG CTAATTTTTTAGGGA-3Ј). PCR and direct DNA sequencing of PCR products were performed as previously described (45). The resulting sequences with evidence of polymorphic residues, thus indicating the presence of multiple templates, were excluded from our analyses.…”

Section: Methodsmentioning

confidence: 99%

Multiple Viral Genetic Analyses Detect Low-Level Human Immunodeficiency Virus Type 1 Replication during Effective Highly Active Antiretroviral Therapy

Frenkel¹,

Wang²,

Learn³

et al. 2003

J Virol

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To evaluate human immunodeficiency virus type 1 (HIV-1) replication and selection of drug-resistant viruses during seemingly effective highly active antiretroviral therapy (HAART), multiple HIV-1 env and pol sequences were analyzed and viral DNA levels were quantified from nucleoside analog-experienced children prior to and during a median of 5.1 (range, 1.8 to 6.4) years of HAART. Viral replication was detected at different rates, with apparently increasing sensitivity: 1 of 10 by phylogenetic analysis; 2 of 10 by viral evolution with increasing genetic distances from the most recent common ancestor (MRCA) of infection; 3 of 10 by selection of drug-resistant mutants; and 6 of 10 by maintenance of genetic distances from the MRCA. When four-or five-drug antiretroviral regimens were given to these children, persistent plasma viral rebound did not occur despite the accumulation of highly drug-resistant genotypes. Among the four children without genetic evidence of viral replication, a statistically significant decrease in the genetic distance to the MRCA was detected in three, indicating the persistence of a greater number of early compared to recent viruses, and their HIV-1 DNA decreased by >0.9 log 10 , resulting in lower absolute DNA levels (P ‫؍‬ 0.007). This study demonstrates the variable rates of viral replication when HAART has suppressed plasma HIV-1 RNA for years to a median of <50 copies/ml and that combinations of four or five antiretroviral drugs suppress viral replication even after short-term virologic failure of three-drug HAART and despite ongoing accumulation of drug-resistant mutants. Furthermore, the decrease of cellular HIV-1 DNA to low absolute levels in those without genetic evidence of viral replication suggests that monitoring viral DNA during HAART may gauge low-level replication.

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“…Sequences were aligned collectively by using CLUSTALX (29) and were then manually adjusted within subjects. Gaps were removed in a balanced manner to preserve codon alignment (30). An earlier study (4) of the eight homologous sequence alignments using traditional codon models of substitution showed that the broad genetic diversity of HIV-1 in infected individuals is a consequence of site-specific positive selection, a likely consequence of immune recognition.…”

Section: Rvmentioning

confidence: 99%

Modeling the site-specific variation of selection patterns along lineages

Guindon

Rodrigo

Dyer

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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177

158

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The unambiguous footprint of positive Darwinian selection in protein-coding DNA sequences is revealed by an excess of nonsynonymous substitutions over synonymous substitutions compared with the neutral expectation. Methods for analyzing the patterns of nonsynonymous and synonymous substitutions usually rely on stochastic models in which the selection regime may vary across the sequence but remains constant across lineages for any amino acid position. Despite some work that has relaxed the constraint that selection patterns remain constant over time, no model provides a strong statistical framework to deal with switches between selection processes at individual sites during the course of evolution. This paper describes an approach that allows the site-specific selection process to vary along lineages of a phylogenetic tree. The parameters of the switching model of codon substitution are estimated by using maximum likelihood. The analysis of eight HIV-1 env homologous sequence data sets shows that this model provides a significantly better fit to the data than one that does not take into account switches between selection patterns in the phylogeny at individual sites. We also provide strong evidence that the strength and the frequency of occurrence of selection might not be estimated accurately when the sitespecific variation of selection regimes is ignored.positive selection ͉ codon-based model of nucleotide substitutions ͉ phylogeny ͉ maximum likelihood A n excess of nonsynonymous changes to synonymous changes in protein-coding DNA sequences is an unambiguous signature of adaptive molecular evolution (1). Such a pattern is best explained by a selective advantage in the past for substitutions that cause amino acid changes. Indeed, there are numerous examples where substitutions causing amino acid changes confer a selective advantage. For example, in the MHC, overdominant selection appears to be responsible for the excess of replacement substitutions in the antigen-recognition site (1). Similarly, positive selection has been detected in viral proteins subject to immune surveillance (2-4), in abalone sperm lysins (5), primate lysozymes (6), and regions involved in species-specific spermegg interaction (7).A number of methods have been proposed to estimate the number of nonsynonymous and synonymous substitutions per site between two homologous sequences (e.g., refs. 8-10). These approaches aim to estimate the ratio between the number of nonsynonymous (and synonymous) substitutions per codon and the number of nonsynonymous (and synonymous) mutations per codon. Simulations have shown that some of these methods provide reliable average estimates of the nonsynonymous͞ synonymous rate ratio (10). However, these approaches assume that amino acids in the sequence evolve under the same selection pressure. This assumption is unrealistic because only a few amino acid sites are found to be responsible for adaptive evolution in almost all proteins that evolve under positive selection (1, 2, 11). As a result, these methods have ...

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Sampling and Processing HIV Molecular Sequences: A Computational Evolutionary Biologist’s Perspective

Cited by 8 publications

References 18 publications

Evolution ofCONSTANSRegulation and Function after Gene Duplication Produced a Photoperiodic Flowering Switch in the Brassicaceae

Evolution ofCONSTANSRegulation and Function after Gene Duplication Produced a Photoperiodic Flowering Switch in the Brassicaceae

Multiple Viral Genetic Analyses Detect Low-Level Human Immunodeficiency Virus Type 1 Replication during Effective Highly Active Antiretroviral Therapy

Modeling the site-specific variation of selection patterns along lineages

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