scholarly journals Amylasecopy number analysis in several mammalian lineages reveals convergent adaptive bursts shaped by diet

2018 ◽  
Author(s):  
Petar Pajic ◽  
Pavlos Pavlidis ◽  
Kirsten Dean ◽  
Lubov Neznanova ◽  
Erin Daugherity ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Copy Number ◽  
Mammalian Species ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Adaptive Mechanism ◽  
Amylase Gene ◽  
Present Evidence ◽  
Copy Number Amplification

AbstractThe amylase gene (AMY), which codes for a starch-digesting enzyme in animals, underwent several gene copy number gains in humans1, dogs2, and mice3, presumably along with increased starch consumption during the evolution of these species. Here we present evidence for additionalAMYcopy number expansions in several mammalian species, most of which also consume starch-rich diets. We also show that these independentAMYcopy number gains are often accompanied by a gain in enzymatic activity of amylase in saliva. We used multi-species coalescent modeling to provide further evidence that these recurrentAMYgene copy number expansions were adaptive. Our findings underscore the overall importance of gene copy number amplification as a flexible and fast adaptive mechanism in evolution that can independently occur in different branches of the phylogeny.

scholarly journals Independent amylase gene copy number bursts correlate with dietary preferences in mammals

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Petar Pajic ◽  
Pavlos Pavlidis ◽  
Kirsten Dean ◽  
Lubov Neznanova ◽  
Rose-Anne Romano ◽  
...  
Keyword(s):  
Copy Number ◽  
Mammalian Species ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Gene Duplications ◽  
Amylase Gene ◽  
Evolutionary Mechanism ◽  
Dietary Preferences ◽  
Copy Number Amplification

The amylase gene (AMY), which codes for a starch-digesting enzyme in animals, underwent several gene copy number gains in humans (Perry et al., 2007), dogs (Axelsson et al., 2013), and mice (Schibler et al., 1982), possibly along with increased starch consumption during the evolution of these species. Here, we present comprehensive evidence for AMY copy number expansions that independently occurred in several mammalian species which consume diets rich in starch. We also provide correlative evidence that AMY gene duplications may be an essential first step for amylase to be expressed in saliva. Our findings underscore the overall importance of gene copy number amplification as a flexible and fast evolutionary mechanism that can independently occur in different branches of the phylogeny.

scholarly journals Emergence of a Viral RNA Polymerase Variant during Gene Copy Number Amplification Promotes Rapid Evolution of Vaccinia Virus

2016 ◽  
Vol 91 (4) ◽  
Author(s):  
Kelsey R. Cone ◽  
Zev N. Kronenberg ◽  
Mark Yandell ◽  
Nels C. Elde
Keyword(s):  
Rna Polymerase ◽  
Vaccinia Virus ◽  
Copy Number ◽  
Point Mutations ◽  
Gene Copy Number ◽  
Viral Rna ◽  
Gene Copy ◽  
Trade Offs ◽  
Number Variation ◽  
Copy Number Amplification

ABSTRACT Viruses are under relentless selective pressure from host immune defenses. To study how poxviruses adapt to innate immune detection pathways, we performed serial vaccinia virus infections in primary human cells. Independent courses of experimental evolution with a recombinant strain lacking E3L revealed several high-frequency point mutations in conserved poxvirus genes, suggesting important roles for essential poxvirus proteins in innate immune subversion. Two distinct mutations were identified in the viral RNA polymerase gene A24R, which seem to act through different mechanisms to increase virus replication. Specifically, a Leu18Phe substitution encoded within A24R conferred fitness trade-offs, including increased activation of the antiviral factor protein kinase R (PKR). Intriguingly, this A24R variant underwent a drastic selective sweep during passaging, despite enhanced PKR activity. We showed that the sweep of this variant could be accelerated by the presence of copy number variation (CNV) at the K3L locus, which in multiple copies strongly reduced PKR activation. Therefore, adaptive cases of CNV can facilitate the accumulation of point mutations separate from the expanded locus. This study reveals how rapid bouts of gene copy number amplification during accrual of distant point mutations can potently facilitate poxvirus adaptation to host defenses. IMPORTANCE Viruses can evolve quickly to defeat host immune functions. For poxviruses, little is known about how multiple adaptive mutations emerge in populations at the same time. In this study, we uncovered a means of vaccinia virus adaptation involving the accumulation of distinct genetic variants within a single population. We identified adaptive point mutations in the viral RNA polymerase gene A24R and, surprisingly, found that one of these mutations activates the nucleic acid sensing factor PKR. We also found that gene copy number variation (CNV) can provide dual benefits to evolving virus populations, including evidence that CNV facilitates the accumulation of a point mutation distant from the expanded locus. Our data suggest that transient CNV can accelerate the fixation of mutations conferring modest benefits, or even fitness trade-offs, and highlight how structural variation might aid poxvirus adaptation through both direct and indirect actions.

scholarly journals Pretreatment Prevotella-to-Bacteroides ratio and salivary amylase gene copy number as prognostic markers for dietary weight loss

2020 ◽  
Vol 111 (5) ◽  
pp. 1079-1086 ◽  
Author(s):  
Mads F Hjorth ◽  
Lars Christensen ◽  
Thomas M Larsen ◽  
Henrik M Roager ◽  
Lukasz Krych ◽  
...  
Keyword(s):  
Weight Loss ◽  
Weight Change ◽  
Copy Number ◽  
Gene Copy Number ◽  
Diet Group ◽  
Gene Copy ◽  
Whole Grain ◽  
Amylase Gene ◽  
Salivary Amylase ◽  
To Receive

ABSTRACT Background The inconsistent link observed between salivary amylase gene copy number (AMY1 CN) and weight management is likely modified by diet and microbiome. Objective Based on analysis of a previously published study, we investigated the hypothesis that interaction between diet, Prevotella-to-Bacteriodes ratio (P/B ratio), and AMY1 CN influence weight change. Methods Sixty-two people with increased waist circumference were randomly assigned to receive an ad libitum New Nordic Diet (NND) high in dietary fiber, whole grain, intrinsic sugars, and starch or an Average Danish (Western) Diet (ADD) for 26 weeks. All foods were provided free of charge. Before subjects were randomly assigned to receive the NND or ADD diet, blood and fecal samples were collected, from which AMY1 CN and P/B ratio, respectively, were determined. Body weight change was described by using linear mixed models, including biomarker [log10(P/B ratio) and/or AMY1 CN] diet-group interactions. Results Baseline means ± SDs of log10(P/B ratio) and AMY1 CN were −2.1 ± 1.8 and 6.6 ± 2.4, respectively. Baseline P/B ratio predicted a 0.99-kg/unit (95% CI: 0.40, 1.57; n = 54; P < 0.001) higher weight loss for those subjects on the NND compared with those on the ADD diet, whereas AMY1 CN was not found to predict weight loss differences between the NND and ADD groups [0.05 kg/CN (95% CI: −0.40, 0.51; n = 54; P = 0.83)]. However, among subjects with low AMY1 CN (<6.5 copies), baseline P/B ratio predicted a 2.12-kg/unit (95% CI: 1.37, 2.88; n = 30; P < 0.001) higher weight loss for the NND group than the ADD group. No such differences in weight loss were found among subjects in both groups with high AMY1 CN [−0.17 kg/unit (95% CI: −1.01, 0.66; n = 24; P = 0.68)]. Conclusions The combined use of low AMY1 CN and pretreatment P/B ratio for weight loss prediction led to highly individualized weight loss results with the introduction of more fiber, whole grain, intrinsic sugars, and starch in the diet. These preliminary observations suggest that more undigested starch reaches the colon in individuals with low AMY1 CN, and that the fate of this starch depends on the gut microbiota composition. This trial was registered at clinicaltrials.gov as NCT01195610.

scholarly journals Directed gene copy number amplification inPichia pastorisby vector integration into the ribosomal DNA locus

2009 ◽  
Vol 9 (8) ◽  
pp. 1260-1270 ◽  
Author(s):  
Hans Marx ◽  
Astrid Mecklenbräuker ◽  
Brigitte Gasser ◽  
Michael Sauer ◽  
Diethard Mattanovich
Keyword(s):  
Ribosomal Dna ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Vector Integration ◽  
Copy Number Amplification

scholarly journals Human amylase gene copy number variation as a determinant of metabolic state

2018 ◽  
Vol 13 (4) ◽  
pp. 193-205 ◽  
Author(s):  
Patrick J.D. Elder ◽  
David B. Ramsden ◽  
David Burnett ◽  
Martin O. Weickert ◽  
Thomas M. Barber
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Amylase Gene ◽  
Metabolic State ◽  
Gene Copy Number Variation ◽  
Number Variation

scholarly journals Diet and the evolution of human amylase gene copy number variation

2007 ◽  
Vol 39 (10) ◽  
pp. 1256-1260 ◽  
Author(s):  
George H Perry ◽  
Nathaniel J Dominy ◽  
Katrina G Claw ◽  
Arthur S Lee ◽  
Heike Fiegler ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Amylase Gene ◽  
Gene Copy Number Variation ◽  
Number Variation

scholarly journals Accelerated selection of a viral RNA polymerase variant during gene copy number amplification promotes rapid evolution of vaccinia virus

2016 ◽  
Author(s):  
Kelsey R. Cone ◽  
Zev N. Kronenberg ◽  
Mark Yandell ◽  
Nels C. Elde
Keyword(s):  
Rna Polymerase ◽  
Vaccinia Virus ◽  
Copy Number ◽  
Point Mutations ◽  
Gene Copy Number ◽  
Viral Rna ◽  
Gene Copy ◽  
Number Variation ◽  
Fitness Tradeoffs ◽  
Copy Number Amplification

AbstractViruses are under relentless selective pressure from host immune defenses. To study how poxviruses adapt to innate immune detection pathways, we performed serial infections of vaccinia virus in primary human cells. Independent courses of experimental evolution with a recombinant strain lacking E3L revealed several high frequency point mutations in conserved poxvirus genes, suggesting important roles for essential poxvirus proteins in innate immune subversion. Two distinct mutations were identified in the viral RNA polymerase gene A24R, which seem to act through different mechanisms to increase virus replication. Specifically, a Leu18Phe substitution in A24R conferred fitness tradeoffs, including increased activation of the antiviral factor Protein kinase R (PKR). Intriguingly, this A24R variant underwent a drastic selective sweep during passaging, despite enhanced PKR activity. We show that the sweep of this variant can be accelerated by the presence of copy number variation (CNV) at the K3L locus, which with multiple copies strongly reduces PKR activation. Therefore, adaptive cases of CNV can also facilitate the accumulation of point mutations separate from the expanded locus. This study reveals how rapid bouts of gene copy number amplification during accrual of distant point mutations can potently facilitate poxvirus adaptation to host defenses.ImportanceViruses can quickly evolve to defeat host immune functions. For poxviruses, little is known about how multiple adaptive mutations might concurrently emerge in populations. In this study, we uncovered a means of vaccinia virus adaptation involving the accumulation of distinct genetic variants within a single population. We identified adaptive point mutations in the viral RNA polymerase gene A24R, and show that these mutations can affect the activation of host nucleic acid sensing pathways through different mechanisms. We also found that structural variants within viral genomes in the form of gene copy number variation (CNV) provide dual benefits to evolving populations, including evidence that CNV facilitates the accumulation of a point mutation distant from the expanded locus. Our data suggest that transient CNV can accommodate the accumulation of mutations conferring modest benefits, or even fitness tradeoffs, and highlight how structural variation might aid poxvirus adaptation through both direct and indirect action.

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