scholarly journals Evolution of subgenomic RNA shapes dengue virus adaptation and epidemiological fitness

2018 ◽  
Author(s):  
Esteban Finol ◽  
Eng Eong Ooi
Keyword(s):  
Dengue Virus ◽  
Positive Selection ◽  
Protein Interactions ◽  
Untranslated Region ◽  
Sequence Divergence ◽  
Purifying Selection ◽  
Viral Fitness ◽  
List Type ◽  
Nucleotide Substitutions ◽  
Genetic Changes

AbstractGenetic changes in the dengue virus (DENV) genome affects viral fitness both clinically and epidemiologically. Even in the 3’ untranslated region (3’UTR), mutations could impact the formation of subgenomic flaviviral RNA (sfRNA) and the specificity of sfRNA in inhibiting host proteins necessary for successful viral replication. Indeed, we have recently shown that mutations in the 3’UTR of DENV2 affected its ability to inhibit TRIM25 E3 ligase activity to reduce interferon (IFN) expression, which potentially contributed to the emergence of a new viral clade during the 1994 dengue epidemic in Puerto Rico. However, whether differences in 3’UTRs shaped DENV evolution on a larger scale remains incompletely understood. Herein, we combined RNA phylogeny with phylogenetics to gain insights on sfRNA evolution. We found that sfRNA structures are under purifying selection and highly conserved despite sequence divergence. Interestingly, only the second flaviviral Nuclease-resistant RNA (fNR2) structure of DENV-2 has undergone strong positive selection. Epidemiological reports also suggest that nucleotide substitutions in fNR2 may drive DENV-2 epidemiological fitness, possibly through sfRNA-protein interactions. Collectively, our findings indicate that 3’UTRs are important determinants of DENV fitness in human-mosquito cycles.HighlightsDengue viruses (DENV) preserve RNA elements in their 3’ untranslated region (UTR).Site-specific quantification of natural selection revealed positive selection on DENV2 sfRNA.Flaviviral nuclease-resistant RNA (fNR) structures in DENV 3’UTRs contribute to DENV speciation.A highly evolving fNR structure appears to increase DENV-2 epidemiological fitness.

scholarly journals Crossing fitness valleys via double substitutions within codons

BMC Biology ◽  
2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Frida Belinky ◽  
Itamar Sela ◽  
Igor B. Rogozin ◽  
Eugene V. Koonin
Keyword(s):  
Amino Acid ◽  
Positive Selection ◽  
Fitness Landscape ◽  
Purifying Selection ◽  
Second Step ◽  
Nucleotide Substitutions ◽  
Protein Coding ◽  
Synonymous Substitutions ◽  
Ancestral States ◽  
Double Substitution

Abstract Background Single nucleotide substitutions in protein-coding genes can be divided into synonymous (S), with little fitness effect, and non-synonymous (N) ones that alter amino acids and thus generally have a greater effect. Most of the N substitutions are affected by purifying selection that eliminates them from evolving populations. However, additional mutations of nearby bases potentially could alleviate the deleterious effect of single substitutions, making them subject to positive selection. To elucidate the effects of selection on double substitutions in all codons, it is critical to differentiate selection from mutational biases. Results We addressed the evolutionary regimes of within-codon double substitutions in 37 groups of closely related prokaryotic genomes from diverse phyla by comparing the fractions of double substitutions within codons to those of the equivalent double S substitutions in adjacent codons. Under the assumption that substitutions occur one at a time, all within-codon double substitutions can be represented as “ancestral-intermediate-final” sequences (where “intermediate” refers to the first single substitution and “final” refers to the second substitution) and can be partitioned into four classes: (1) SS, S intermediate–S final; (2) SN, S intermediate–N final; (3) NS, N intermediate–S final; and (4) NN, N intermediate–N final. We found that the selective pressure on the second substitution markedly differs among these classes of double substitutions. Analogous to single S (synonymous) substitutions, SS double substitutions evolve neutrally, whereas analogous to single N (non-synonymous) substitutions, SN double substitutions are subject to purifying selection. In contrast, NS show positive selection on the second step because the original amino acid is recovered. The NN double substitutions are heterogeneous and can be subject to either purifying or positive selection, or evolve neutrally, depending on the amino acid similarity between the final or intermediate and the ancestral states. Conclusions The results of the present, comprehensive analysis of the evolutionary landscape of within-codon double substitutions reaffirm the largely conservative regime of protein evolution. However, the second step of a double substitution can be subject to positive selection when the first step is deleterious. Such positive selection can result in frequent crossing of valleys on the fitness landscape.

scholarly journals HD-AGPs as Speciation Genes: Positive Selection on a Proline-Rich Domain in Non-Hybridizing Species of Petunia, Solanum, and Nicotiana

Plants ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 211 ◽  
Author(s):  
Tara D. Callaway ◽  
Anu Singh-Cundy
Keyword(s):  
Positive Selection ◽  
Seed Set ◽  
Sequence Divergence ◽  
Ecological Factors ◽  
Purifying Selection ◽  
Rich Region ◽  
Rich Domain ◽  
Species Pairs ◽  
Specific Proteins ◽  
Petunia Integrifolia

Transmitting tissue-specific proteins (TTS proteins) are abundant in the extracellular matrix of Nicotiana pistils, and vital for optimal pollen tube growth and seed set. We have identified orthologs from several species in the Solanaceae, including Petunia axillaris axillaris and Petunia integrifolia. We refer to TTS proteins and their orthologs as histidine domain-arabinogalactan proteins (HD-APGs). HD-AGPs have distinctive domains, including a small histidine-rich region and a C-terminal PAC domain. Pairwise comparisons between HD-AGPs of 15 species belonging to Petunia, Nicotiana, and Solanum show that the his-domain and PAC domain are under purifying selection. In contrast, a proline-rich domain (HV2) is conserved among cross-hybridizing species, but variant in species-pairs that are reproductively isolated by post-pollination pre-fertilization reproductive barriers. In particular, variation in a tetrapeptide motif (XKPP) is systematically correlated with the presence of an interspecific reproductive barrier. Ka/Ks ratios are not informative at the infrageneric level, but the ratios reveal a clear signature of positive selection on two hypervariable domains (HV1 and HV2) when HD-AGPs from five solanaceous genera are compared. We propose that sequence divergence in the hypervariable domains of HD-AGPs reinforces sympatric speciation in incipient species that may have first diverged as a consequence of pollinator preferences or other ecological factors.

scholarly journals Positive selection and intrinsic disorder are associated with multifunctional C4(AC4) proteins and geminivirus diversification

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Carl Michael Deom ◽  
Marin Talbot Brewer ◽  
Paul M. Severns
Keyword(s):  
Positive Selection ◽  
Purifying Selection ◽  
Intrinsic Disorder ◽  
Functional Variation ◽  
Nucleotide Substitutions ◽  
Protein Diversity ◽  
Synonymous Mutations ◽  
Intrinsically Disordered ◽  
Associated Proteins ◽  
Host Jumping

AbstractViruses within the Geminiviridae family cause extensive agricultural losses. Members of four genera of geminiviruses contain a C4 gene (AC4 in geminiviruses with bipartite genomes). C4(AC4) genes are entirely overprinted on the C1(AC1) genes, which encode the replication-associated proteins. The C4(AC4) proteins exhibit diverse functions that may be important for geminivirus diversification. In this study, the influence of natural selection on the evolutionary diversity of 211 C4(AC4) genes relative to the C1(AC1) sequences they overlap was determined from isolates of the Begomovirus and Curtovirus genera. The ratio of nonsynonymous (dN) to synonymous (dS) nucleotide substitutions indicated that C4(AC4) genes are under positive selection, while the overlapped C1(AC1) sequences are under purifying selection. Ninety-one of 200 Begomovirus C4(AC4) genes encode elongated proteins with the extended regions being under neutral selection. C4(AC4) genes from begomoviruses isolated from tomato from native versus exotic regions were under similar levels of positive selection. Analysis of protein structure suggests that C4(AC4) proteins are entirely intrinsically disordered. Our data suggest that non-synonymous mutations and mutations that increase the length of C4(AC4) drive protein diversity that is intrinsically disordered, which could explain C4/AC4 functional variation and contribute to both geminivirus diversification and host jumping.

scholarly journals Crossing fitness valleys via double substitutions within codons

2019 ◽  
Author(s):  
Frida Belinky ◽  
Itamar Sela ◽  
Igor B. Rogozin ◽  
Eugene V. Koonin
Keyword(s):  
Amino Acid ◽  
Positive Selection ◽  
Deleterious Effect ◽  
Fitness Landscape ◽  
Purifying Selection ◽  
Nucleotide Substitutions ◽  
Fitness Effect ◽  
Single Nucleotide ◽  
Protein Coding ◽  
Ancestral States

AbstractSingle nucleotide substitutions in protein-coding genes can be divided into synonymous (S), with little fitness effect, and non-synonymous (N) ones that alter amino acids and thus generally have a greater effect. Most of the N substitutions are affected by purifying selection that eliminates them from evolving populations. However, additional mutations of nearby bases can modulate the deleterious effect of single substitutions and thus might be subject to positive selection. To elucidate the effects of selection on double substitutions in all codons, it is critical to differentiate selection from mutational biases. We approached this problem by comparing the fractions of double substitutions within codons to those of the equivalent double S substitutions in adjacent codons. Under the assumption that substitutions occur one at a time, all within-codon double substitutions can be represented as “ancestral-intermediate-final” sequences and can be partitioned into 4 classes: 1) SS: S intermediate – S final, 2) SN: S intermediate – N final, 3) NS: N intermediate – S final, 4) NN: N intermediate – N final. We found that the selective pressure on the second substitution markedly differs among these classes of double substitutions. Analogous to single S substitutions, SS evolve neutrally whereas, analogous to single N substitutions, SN are subject to purifying selection. In contrast, NS show positive selection on the second step because the original amino acid is recovered. The NN double substitutions are heterogeneous and can be subject to either purifying or positive selection, or evolve neutrally, depending on the amino acid similarity between the final or intermediate and the ancestral states. The general trend is that the second mutation compensates for the deleterious effect of the first one, resulting in frequent crossing of valleys on the fitness landscape.

scholarly journals Universal patterns of selection in cancer and somatic tissues

2017 ◽  
Author(s):  
Iñigo Martincorena ◽  
Keiran M. Raine ◽  
Moritz Gerstung ◽  
Kevin J. Dawson ◽  
Kerstin Haase ◽  
...  
Keyword(s):  
Positive Selection ◽  
Negative Selection ◽  
Clonal Selection ◽  
Purifying Selection ◽  
Driver Mutations ◽  
Base Substitution ◽  
List Type ◽  
Cancer Genes ◽  
Cancer Evolution ◽  
Mutation Burden

ABSTRACTCancer develops as a result of somatic mutation and clonal selection, but quantitative measures of selection in cancer evolution are lacking. We applied methods from evolutionary genomics to 7,664 human cancers across 29 tumor types. Unlike species evolution, positive selection outweighs negative selection during cancer development. On average, <1 coding base substitution/tumor is lost through negative selection, with purifying selection only detected for truncating mutations in essential genes in haploid regions. This allows exome-wide enumeration of all driver mutations, including outside known cancer genes. On average, tumors carry ∼4 coding substitutions under positive selection, ranging from <1/tumor in thyroid and testicular cancers to >10/tumor in endometrial and colorectal cancers. Half of driver substitutions occur in yet-to-be-discovered cancer genes. With increasing mutation burden, numbers of driver mutations increase, but not linearly. We identify novel cancer genes and show that genes vary extensively in what proportion of mutations are drivers versus passengers.HIGHLIGHTSUnlike the germline, somatic cells evolve predominantly by positive selectionNearly all (∼99%) coding mutations are tolerated and escape negative selectionFirst exome-wide estimates of the total number of driver coding mutations per tumor1-10 coding driver mutations per tumor; half occurring outside known cancer genes

scholarly journals Protein Coding Gene Nucleotide Substitution Pattern in the Apicomplexan ProtozoaCryptosporidium parvumandCryptosporidium hominis

2008 ◽  
Vol 2008 ◽  
pp. 1-6 ◽  
Author(s):  
Guangtao Ge ◽  
Lenore Cowen ◽  
Xiaochuan Feng ◽  
Giovanni Widmer
Keyword(s):  
Positive Selection ◽  
Purifying Selection ◽  
High Ratio ◽  
Genome Comparison ◽  
Nucleotide Substitutions ◽  
Substitution Pattern ◽  
Protein Coding ◽  
Genome Wide ◽  
The Impact ◽  
Selection Of

Cryptosporidium parvumandC. hominisare related protozoan pathogens which infect the intestinal epithelium of humans and other vertebrates. To explore the evolution of these parasites, and identify genes under positive selection, we performed a pairwise whole-genome comparison between all orthologous protein coding genes inC. parvumandC. hominis. Genome-wide calculation of the ratio of nonsynonymous versus synonymous nucleotide substitutions (dN/dS) was performed to detect the impact of positive and purifying selection. Of 2465 pairs of orthologous genes, a total of 27 (1.1%) showed a high ratio of nonsynonymous substitutions, consistent with positive selection. A majority of these genes were annotated as hypothetical proteins. In addition, proteins with transmembrane and signal peptide domains are significantly more frequent in the highdN/dSgroup.

scholarly journals Dengue virus strain 2 capsid protein switches the annealing pathway and reduces intrinsic dynamics of the conserved 5’ untranslated region

RNA Biology ◽  
2021 ◽  
pp. 1-14
Author(s):  
Xin Ee Yong ◽  
Palur Venkata Raghuvamsi ◽  
Ganesh S. Anand ◽  
Thorsten Wohland ◽  
Kamal K. Sharma
Keyword(s):  
Dengue Virus ◽  
Capsid Protein ◽  
Virus Strain ◽  
Untranslated Region

Sequence variation and evolution of nuclear DNA in man and the primates

1981 ◽  
Vol 292 (1057) ◽  
pp. 133-142 ◽  
Keyword(s):  
Dna Sequence ◽  
Sequence Variation ◽  
Nuclear Dna ◽  
Sequence Divergence ◽  
Gene Arrangement ◽  
Human Populations ◽  
Genetic Changes ◽  
Detailed Structural Analysis ◽  
Dna Sequence Variation ◽  
History Of

Recent advances in nucleic acid technology have facilitated the detection and detailed structural analysis of a wide variety of genes in higher organisms, including those in man. This in turn has opened the way to an examination of the evolution of structural genes and their surrounding and intervening sequences. In a study of the evolution of haemoglobin genes and neighbouring sequences in man and the primates, we have investigated gene arrangement and DNA sequence divergence both within and between species ranging from Old World monkeys to man. This analysis is beginning to reveal the evolutionary constraints that have acted on this region of the genome during primate evolution. Furthermore, DNA sequence variation, both within and between species, provides, in principle, a novel and powerful method for determining inter-specific phylogenetic distances and also for analysing the structure of present-day human populations. Application of this new branch of molecular biology to other areas of the human genome should prove important in unravelling the history of genetic changes that have occurred during the evolution of man.

scholarly journals Genetic Diversity and Potential Vectors and Reservoirs of Cucurbit aphid-borne yellows virus in Southeastern Spain

2013 ◽  
Vol 103 (11) ◽  
pp. 1188-1197 ◽  
Author(s):  
Mona A. Kassem ◽  
Miguel Juarez ◽  
Pedro Gómez ◽  
Carmen M. Mengual ◽  
Raquel N. Sempere ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Aphis Gossypii ◽  
Purifying Selection ◽  
Aphid Species ◽  
Open Reading Frames ◽  
Weed Species ◽  
Nucleotide Substitutions ◽  
Multiple Introductions ◽  
Spatial And Temporal Scales ◽  
Southeastern Spain

The genetic variability of a Cucurbit aphid-borne yellows virus (CABYV) (genus Polerovirus, family Luteoviridae) population was evaluated by determining the nucleotide sequences of two genomic regions of CABYV isolates collected in open-field melon and squash crops during three consecutive years in Murcia (southeastern Spain). A phylogenetic analysis showed the existence of two major clades. The sequences did not cluster according to host, year, or locality of collection, and nucleotide similarities among isolates were 97 to 100 and 94 to 97% within and between clades, respectively. The ratio of nonsynonymous to synonymous nucleotide substitutions reflected that all open reading frames have been under purifying selection. Estimates of the population's genetic diversity were of the same magnitude as those previously reported for other plant virus populations sampled at larger spatial and temporal scales, suggesting either the presence of CABYV in the surveyed area long before it was first described, multiple introductions, or a particularly rapid diversification. We also determined the full-length sequences of three isolates, identifying the occurrence and location of recombination events along the CABYV genome. Furthermore, our field surveys indicated that Aphis gossypii was the major vector species of CABYV and the most abundant aphid species colonizing melon fields in the Murcia (Spain) region. Our surveys also suggested the importance of the weed species Ecballium elaterium as an alternative host and potential virus reservoir.

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