scholarly journals False-positive results obtained from the branch-site test of positive selection

2008 ◽  
Vol 83 (4) ◽  
pp. 331-338 ◽  
Author(s):  
Yoshiyuki Suzuki
Keyword(s):  
Positive Selection ◽  
False Positive ◽  
Branch Site ◽  
Site Test ◽  
Positive Results

scholarly journals Detection of pathways affected by positive selection in primate lineages ancestral to humans

2016 ◽  
Author(s):  
J.T. Daub ◽  
S. Moretti ◽  
I. I. Davidov ◽  
L. Excoffier ◽  
M. Robinson-Rechavi
Keyword(s):  
Positive Selection ◽  
Functional Enrichment ◽  
Gene Trees ◽  
Gene Set Enrichment ◽  
Protein Coding ◽  
Gene Set ◽  
Branch Site ◽  
Gene Sets ◽  
Site Test ◽  
Polygenic Selection

AbstractGene set enrichment approaches have been increasingly successful in finding signals of recent polygenic selection in the human genome. In this study, we aim at detecting biological pathways affected by positive selection in more ancient human evolutionary history. Focusing on four branches of the primate tree that lead to modern humans, we tested all available protein coding gene trees of the Primates clade for signals of adaptation in these branches, using the likelihood-based branch site test of positive selection. The results of these locus-specific tests were then used as input for a gene set enrichment test, where whole pathways are globally scored for a signal of positive selection, instead of focusing only on outlier “significant” genes. We identified signals of positive selection in several pathways that are mainly involved in immune response, sensory perception, metabolism, and energy production. These pathway-level results are highly significant, even though there is no functional enrichment when only focusing on top scoring genes. Interestingly, several gene sets are found significant at multiple levels in the phylogeny, but different genes are responsible for the selection signal in the different branches. This suggests that the same function has been optimized in different ways at different times in primate evolution.

scholarly journals Evolutionary analysis of vision genes identifies potential drivers of visual differences between giraffe and okapi

2016 ◽  
Author(s):  
Edson Ishengoma ◽  
Morris Agaba ◽  
Douglas R Cavener
Keyword(s):  
Positive Selection ◽  
Visual Signal ◽  
Evolutionary Analysis ◽  
Long Distance ◽  
Phenotypic Differences ◽  
Multiple Strategies ◽  
Branch Site ◽  
Signature Of Selection ◽  
Evolutionary Success ◽  
Site Test

Background. The capacity of species to respond and perceive visual signal is integral to their evolutionary success. Giraffe is closely related to okapi, but the two species have broad range of phenotypic differences including their visual capacities. Vision studies rank giraffe’s visual acuity higher than all other artiodactyls despite sharing similar vision ecological determinants with most of them. To what extent giraffe unique visual capacity and its difference with okapi is reflected by changes in their vision genes is not understood. Methods. The recent availability of giraffe and okapi genome provided opportunity to identify giraffe and okapi vision genes. Multiple strategies were employed to identify thirty-six candidate mammalian vision genes in giraffe and okapi genomes. Quantification of selection pressure was performed by a combination of branch-site test of positive selection and clade models of selection divergence through comparing giraffe and okapi vision genes and their corresponding orthologous sequences from other mammals obtained from public gene banks. Results. Signatures of selection was identified in key genes that could potentially underlie giraffe and okapi visual adaptations. Importantly, some genes that contribute to optical transparency of the eye and those that are critical in light signaling pathway were found to show signatures of adaptive evolution or selection divergence. Comparison between giraffe and other ruminants identifies significant selection divergence in CRYAA and OPN1LW in giraffe. Significant selection divergence was identified in SAG while positive selection was detected in LUM when okapi is compared with ruminants and other mammals. Sequence analysis of OPN1LW showed that at least one of the sites known to affect spectral sensitivity of the red pigment is uniquely divergent between giraffe and other ruminants. Discussion. By taking a systemic approach to gene function in vision, the results provide the first molecular clues associated with giraffe and okapi vision adaptation. At least some of the genes that exhibit signature of selection may reflect adaptive response to differences in giraffe and okapi habitat. Moreover, requirement for long distance vision associated with predation likely played an important role in the adaptive pressure on giraffe vision genes.

scholarly journals Evolutionary analysis of vision genes identifies potential drivers of visual differences between giraffe and okapi

2016 ◽  
Author(s):  
Edson Ishengoma ◽  
Morris Agaba ◽  
Douglas R Cavener
Keyword(s):  
Positive Selection ◽  
Visual Signal ◽  
Evolutionary Analysis ◽  
Long Distance ◽  
Phenotypic Differences ◽  
Multiple Strategies ◽  
Branch Site ◽  
Signature Of Selection ◽  
Evolutionary Success ◽  
Site Test

Background. The capacity of species to respond and perceive visual signal is integral to their evolutionary success. Giraffe is closely related to okapi, but the two species have broad range of phenotypic differences including their visual capacities. Vision studies rank giraffe’s visual acuity higher than all other artiodactyls despite sharing similar vision ecological determinants with most of them. To what extent giraffe unique visual capacity and its difference with okapi is reflected by changes in their vision genes is not understood. Methods. The recent availability of giraffe and okapi genome provided opportunity to identify giraffe and okapi vision genes. Multiple strategies were employed to identify thirty-six candidate mammalian vision genes in giraffe and okapi genomes. Quantification of selection pressure was performed by a combination of branch-site test of positive selection and clade models of selection divergence through comparing giraffe and okapi vision genes and their corresponding orthologous sequences from other mammals obtained from public gene banks. Results. Signatures of selection was identified in key genes that could potentially underlie giraffe and okapi visual adaptations. Importantly, some genes that contribute to optical transparency of the eye and those that are critical in light signaling pathway were found to show signatures of adaptive evolution or selection divergence. Comparison between giraffe and other ruminants identifies significant selection divergence in CRYAA and OPN1LW in giraffe. Significant selection divergence was identified in SAG while positive selection was detected in LUM when okapi is compared with ruminants and other mammals. Sequence analysis of OPN1LW showed that at least one of the sites known to affect spectral sensitivity of the red pigment is uniquely divergent between giraffe and other ruminants. Discussion. By taking a systemic approach to gene function in vision, the results provide the first molecular clues associated with giraffe and okapi vision adaptation. At least some of the genes that exhibit signature of selection may reflect adaptive response to differences in giraffe and okapi habitat. Moreover, requirement for long distance vision associated with predation likely played an important role in the adaptive pressure on giraffe vision genes.

scholarly journals Multinucleotide mutations cause false inferences of lineage-specific positive selection

2017 ◽  
Author(s):  
Aarti Venkat ◽  
Matthew W. Hahn ◽  
Joseph W. Thornton
Keyword(s):  
Positive Selection ◽  
Adaptive Evolution ◽  
Alternative Model ◽  
Systematic Bias ◽  
Nucleotide Substitutions ◽  
Branch Site ◽  
Genome Wide ◽  
Sequence Patterns ◽  
Site Test ◽  
Mutational Processes

ABSTRACTPhylogenetic tests of adaptive evolution, which infer positive selection from an excess of nonsynonymous changes, assume that nucleotide substitutions occur singly and independently. But recent research has shown that multiple errors at adjacent sites often occur in single events during DNA replication. These multinucleotide mutations (MNMs) are overwhelmingly likely to be nonsynonymous. We therefore evaluated whether phylogenetic tests of adaptive evolution, such as the widely used branch-site test, might misinterpret sequence patterns produced by MNMs as false support for positive selection. We explored two genome-wide datasets comprising thousands of coding alignments – one from mammals and one from flies – and found that codons with multiple differences (CMDs) account for virtually all the support for lineage-specific positive selection inferred by the branch-site test. Simulations under genome-wide, empirically derived conditions without positive selection show that realistic rates of MNMs cause a strong and systematic bias in the branch-site and related tests; the bias is sufficient to produce false positive inferences approximately as often as the branch-site test infers positive selection from the empirical data. Our analysis indicates that genes may often be inferred to be under positive selection simply because they stochastically accumulated one or a few MNMs. Because these tests do not reliably distinguish sequence patterns produced by authentic positive selection from those caused by neutral fixation of MNMs, many published inferences of adaptive evolution using these techniques may therefore be artifacts of model violation caused by unincorporated neutral mutational processes. We develop an alternative model that incorporates MNMs and may be helpful in reducing this bias.

Critical Evaluation of Impedance Phlebography for the Diagnosis of Deep Vein Thrombosis

1974 ◽  
Vol 31 (02) ◽  
pp. 273-278
Author(s):  
Kenneth K Wu ◽  
John C Hoak ◽  
Robert W Barnes ◽  
Stuart L Frankel
Keyword(s):  
Deep Vein Thrombosis ◽  
False Positive ◽  
False Negative ◽  
Critical Evaluation ◽  
Original Method ◽  
Vein Thrombosis ◽  
Negative Results ◽  
False Negative Results ◽  
Deep Vein ◽  
Positive Results

SummaryIn order to evaluate its daily variability and reliability, impedance phlebography was performed daily or on alternate days on 61 patients with deep vein thrombosis, of whom 47 also had 125I-fibrinogen uptake tests and 22 had radiographic venography. The results showed that impedance phlebography was highly variable and poorly reliable. False positive results were noted in 8 limbs (18%) and false negative results in 3 limbs (7%). Despite its being simple, rapid and noninvasive, its clinical usefulness is doubtful when performed according to the original method.

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