scholarly journals Detecting positive selection within genomes: the problem of biased gene conversion

2010 ◽  
Vol 365 (1552) ◽  
pp. 2571-2580 ◽  
Author(s):  
Abhirami Ratnakumar ◽  
Sylvain Mousset ◽  
Sylvain Glémin ◽  
Jonas Berglund ◽  
Nicolas Galtier ◽  
...  
Keyword(s):  
Positive Selection ◽  
Gene Conversion ◽  
Evolutionary Genetics ◽  
Synonymous Substitution ◽  
Nucleotide Substitutions ◽  
Accelerated Evolution ◽  
A Genome ◽  
Biased Gene Conversion ◽  
Synonymous Substitution Rates ◽  
Wide Scale

The identification of loci influenced by positive selection is a major goal of evolutionary genetics. A popular approach is to perform scans of alignments on a genome-wide scale in order to find regions evolving at accelerated rates on a particular branch of a phylogenetic tree. However, positive selection is not the only process that can lead to accelerated evolution. Notably, GC-biased gene conversion (gBGC) is a recombination-associated process that results in the biased fixation of G and C nucleotides. This process can potentially generate bursts of nucleotide substitutions within hotspots of meiotic recombination. Here, we analyse the results of a scan for positive selection on genes on branches across the primate phylogeny. We show that genes identified as targets of positive selection have a significant tendency to exhibit the genomic signature of gBGC. Using a maximum-likelihood framework, we estimate that more than 20 per cent of cases of significantly elevated non-synonymous to synonymous substitution rates ratio ( d N / d S ), particularly in shorter branches, could be due to gBGC. We demonstrate that in some cases, gBGC can lead to very high d N / d S (more than 2). Our results indicate that gBGC significantly affects the evolution of coding sequences in primates, often leading to patterns of evolution that can be mistaken for positive selection.

Accelerated Evolution of Fetuin-A (FETUA, also AHSG) is Driven by Positive Darwinian Selection, not GC-Biased Gene Conversion

Gene ◽  
2010 ◽  
Vol 463 (1-2) ◽  
pp. 49-55 ◽  
Author(s):  
Yvonne Döring ◽  
Ulrich Zechner ◽  
Christian Roos ◽  
David Rosenkranz ◽  
Hans Zischler ◽  
...  
Keyword(s):  
Gene Conversion ◽  
Positive Darwinian Selection ◽  
Darwinian Selection ◽  
Fetuin A ◽  
Accelerated Evolution ◽  
Biased Gene Conversion

scholarly journals Potent Antibody-Mediated Neutralization and Evolution of Antigenic Escape Variants of Simian Immunodeficiency Virus Strain SIVmac239 In Vivo

2008 ◽  
Vol 82 (19) ◽  
pp. 9739-9752 ◽  
Author(s):  
Shuji Sato ◽  
Eloisa Yuste ◽  
William A. Lauer ◽  
Eun Hyuk Chang ◽  
Jennifer S. Morgan ◽  
...  
Keyword(s):  
Amino Acid ◽  
Time Course ◽  
Neutralizing Antibody ◽  
Synonymous Substitution ◽  
Viral Envelope ◽  
Single Amino Acid ◽  
Nucleotide Substitutions ◽  
Recombinant Viruses ◽  
Synonymous Substitution Rates

ABSTRACT Here, we describe the evolution of antigenic escape variants in a rhesus macaque that developed unusually high neutralizing antibody titers to SIVmac239. By 42 weeks postinfection, 50% neutralization of SIVmac239 was achieved with plasma dilutions of 1:1,000. Testing of purified immunoglobulin confirmed that the neutralizing activity was antibody mediated. Despite the potency of the neutralizing antibody response, the animal displayed a typical viral load profile and progressed to terminal AIDS with a normal time course. Viral envelope sequences from week 16 and week 42 plasma contained an excess of nonsynonymous substitutions, predominantly in V1 and V4, including individual sites with ratios of nonsynonymous to synonymous substitution rates (dN/dS) highly suggestive of strong positive selection. Recombinant viruses encoding envelope sequences isolated from these time points remained resistant to neutralization by all longitudinal plasma samples, revealing the failure of the animal to mount secondary responses to the escaped variants. Substitutions at two sites with significant dN/dS values, one in V1 and one in V4, were independently sufficient to confer nearly complete resistance to neutralization. Substitutions at three additional sites, one in V4 and two in gp41, conferred moderate to high levels of resistance when tested individually. All the amino acid changes leading to escape resulted from single nucleotide substitutions. The observation that antigenic escape resulted from individual, single amino acid replacements at sites well separated in current structural models of Env indicates that the virus can utilize multiple independent pathways to rapidly achieve similar levels of resistance.

scholarly journals Detection of subgenome bias using an anchored syntenic approach in Eleusine coracana (finger millet)

2020 ◽  
Author(s):  
Nathan Daniel Hall ◽  
Jinesh D Patel ◽  
Joseph Scott McElroy ◽  
Leslie Richard Goertzen
Keyword(s):  
Finger Millet ◽  
Draft Genome ◽  
Synonymous Substitution ◽  
Eleusine Coracana ◽  
Eastern Africa ◽  
Syntenic Block ◽  
Individual Gene ◽  
A Genome ◽  
Synonymous Substitution Rates

Abstract Background: Finger millet (Eleusine coracana 2n=4x=36 ) is a hardy, nutraceutical, climate change tolerant, orphan crop that is consumed throughout eastern Africa and India. Its genome has been sequenced multiple times, but A and B subgenomes could not be separated because no published genome for E. indica existed. The classification of A and B subgenomes is important for understanding the evolution of this crop and provide a means to improve current and future breeding programs. Results: We produced subgenome calls for 704 syntenic blocks and inferred A or B subgenomic identity for 59,377 genes 81% of the annotated genes. Phylogenetic analysis of a super matrix containing 455 genes shows high support for A and B divergence within the Eleusine genus. Synonymous substitution rates between A and B genes support A and B calls. The repetitive content on highly supported B contigs is higher than that on similar A contigs. Analysis of syntenic singletons showed evidence of biased fractionation showed a pattern of A genome dominance, with 61% A , 37% B and 1% unassigned, and was further supported by the pattern of loss observed among cyto-nuclear interacting genes. Examination of expression within the circadian rhythm pathway suggests A subgenomic preference. Conclusion: The evidence of individual gene calls within each syntenic block, provides a powerful tool for inference for subgenome classification. Our results show the utility of a draft genome in resolving A and B subgenomes calls, primarily it allows for the proper polarization of A and B syntenic blocks. There have been multiple calls for the use of phylogenetic inference in subgenome classification, our use of synteny is a practical application in a system that has only one parental genome available.

scholarly journals Detection of subgenome bias using an anchored syntenic approach in Eleusine coracana (finger millet)

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Nathan D. Hall ◽  
Jinesh D. Patel ◽  
J. Scott McElroy ◽  
Leslie R. Goertzen
Keyword(s):  
Finger Millet ◽  
Draft Genome ◽  
Synonymous Substitution ◽  
Eleusine Coracana ◽  
Eastern Africa ◽  
Syntenic Block ◽  
Individual Gene ◽  
A Genome ◽  
Synonymous Substitution Rates

AbstractBackgroundFinger millet (Eleusine coracana2n = 4x = 36) is a hardy, nutraceutical, climate change tolerant, orphan crop that is consumed throughout eastern Africa and India. Its genome has been sequenced multiple times, but A and B subgenomes could not be separated because no published genome forE. indicaexisted. The classification of A and B subgenomes is important for understanding the evolution of this crop and provide a means to improve current and future breeding programs.ResultsWe produced subgenome calls for 704 syntenic blocks and inferred A or B subgenomic identity for 59,377 genes 81% of the annotated genes. Phylogenetic analysis of a super matrix containing 455 genes shows high support for A and B divergence within theEleusinegenus. Synonymous substitution rates between A and B genes support A and B calls. The repetitive content on highly supported B contigs is higher than that on similar A contigs. Analysis of syntenic singletons showed evidence of biased fractionation showed a pattern of A genome dominance, with 61% A, 37% B and 1% unassigned, and was further supported by the pattern of loss observed among cyto-nuclear interacting genes.ConclusionThe evidence of individual gene calls within each syntenic block, provides a powerful tool for inference for subgenome classification. Our results show the utility of a draft genome in resolving A and B subgenomes calls, primarily it allows for the proper polarization of A and B syntenic blocks. There have been multiple calls for the use of phylogenetic inference in subgenome classification, our use of synteny is a practical application in a system that has only one parental genome available.

scholarly journals Detection of subgenome bias using an anchored syntenic approach in Eleusine coracana (finger millet)

2021 ◽  
Author(s):  
Nathan Daniel Hall ◽  
Jinesh D Patel ◽  
Joseph Scott McElroy ◽  
Leslie Richard Goertzen
Keyword(s):  
Finger Millet ◽  
Draft Genome ◽  
Synonymous Substitution ◽  
Eleusine Coracana ◽  
Eastern Africa ◽  
Syntenic Block ◽  
Individual Gene ◽  
A Genome ◽  
Synonymous Substitution Rates

Abstract Background: Finger millet (Eleusine coracana 2n=4x=36 ) is a hardy, nutraceutical, climate change tolerant, orphan crop that is consumed throughout eastern Africa and India. Its genome has been sequenced multiple times, but A and B subgenomes could not be separated because no published genome for E. indica existed. The classification of A and B subgenomes is important for understanding the evolution of this crop and provide a means to improve current and future breeding programs. Results: We produced subgenome calls for 704 syntenic blocks and inferred A or B subgenomic identity for 59,377 genes 81% of the annotated genes. Phylogenetic analysis of a super matrix containing 455 genes shows high support for A and B divergence within the Eleusine genus. Synonymous substitution rates between A and B genes support A and B calls. The repetitive content on highly supported B contigs is higher than that on similar A contigs. Analysis of syntenic singletons showed evidence of biased fractionation showed a pattern of A genome dominance, with 61% A , 37% B and 1% unassigned, and was further supported by the pattern of loss observed among cyto-nuclear interacting genes. Examination of transcript counts within the Circadian Rhythm Pathway suggests a possible A subgenomic preference. Conclusion: The evidence of individual gene calls within each syntenic block, provides a powerful tool for inference for subgenome classification. Our results show the utility of a draft genome in resolving A and B subgenomes calls, primarily it allows for the proper polarization of A and B syntenic blocks. There have been multiple calls for the use of phylogenetic inference in subgenome classification, our use of synteny is a practical application in a system that has only one parental genome available.

scholarly journals Genealogical Evidence for Positive Selection in the nef Gene of HIV-1

Genetics ◽  
1999 ◽  
Vol 153 (3) ◽  
pp. 1077-1089
Author(s):  
Paolo M de A. Zanotto ◽  
Esper G Kallas ◽  
Robson F de Souza ◽  
Edward C Holmes
Keyword(s):  
Positive Selection ◽  
Gene Evolution ◽  
Synonymous Substitution ◽  
Good Evidence ◽  
Likelihood Method ◽  
Variable Intensity ◽  
Subtype B ◽  
Synonymous Substitution Rates ◽  
Hiv 1 ◽  
Positively Selected Sites

Abstract The pattern and process of evolution in the nef gene of HIV-1 was analyzed within and among patients. Using a maximum likelihood method that allows for variable intensity of selection pressure among codons, strong positive selection was detected in a hemophiliac patient over 30 mo of infection. By reconstructing the process of allele substitution in this patient using parsimony, the synapomorphic amino acid changes separating each time point were found to have high probabilities of being under positive selection, with selective coefficients of at least 3.6%. Positive selection was also detected among 39 nef sequences from HIV-1 subtype B. In contrast, multiple pairwise comparisons of nonsynonymous and synonymous substitution rates provided no good evidence for positive selection and sliding window analyses failed to detect most positively selected sites. These findings demonstrate that positive selection is an important determinant of nef gene evolution and that genealogy-based methods outperform pairwise methods in the detection of adaptive evolution. Mapping the locations of positively selected sites may also be of use in identifying targets of the immune response and hence aid vaccine design.

scholarly journals Detection of subgenome bias using an anchored syntenic approach in Eleusine coracana (finger millet)

2020 ◽  
Author(s):  
Nathan Daniel Hall ◽  
Jinesh D Patel ◽  
Joseph Scott McElroy ◽  
Leslie Richard Goertzen
Keyword(s):  
Finger Millet ◽  
Draft Genome ◽  
Synonymous Substitution ◽  
Eleusine Coracana ◽  
Eastern Africa ◽  
Syntenic Block ◽  
Individual Gene ◽  
A Genome ◽  
Synonymous Substitution Rates

Abstract Background: Finger millet (Eleusine coracana 2n=4x=36 ) is a hardy, nutraceutical, climate change tolerant, orphan crop that is consumed throughout eastern Africa and India. Its genome has been sequenced multiple times, but A and B subgenomes could not be separated because no published genome for E. indica existed. The classification of A and B subgenomes is important for understanding the evolution of this crop and provide a means to improve current and future breeding programs.Results: We produced subgenome calls for 704 syntenic blocks and inferred A or B subgenomic identity for 59,377 genes 81% of the annotated genes. Phylogenetic analysis of a super matrix containing 455 genes shows high support for A and B divergence within the Eleusine genus. Synonymous substitution rates between A and B genes supports A and B calls. The repetitive content on highly supported B contigs is higher than that on similar A contigs. Analysis of syntenic singletons showed evidence of biased fractionation showed a pattern of A genome dominance, with 61% A , 37% B and 1% unassigned, and was further supported by the pattern of loss observed among cyto-nuclear interacting genes. Examination of expression within the ciradian rhythm pathway suggests A subgenomic preference.Conclusion: The evidence of individual gene calls within each syntenic block, provides a powerful tool for inference for subgenome classification. Our results show the utility of a draft genome in resolving A and B subgenomes calls, primarily it allows for the proper polarization of A and B syntenic blocks. There have been multiple calls for the use of phylogenetic inference in subgenome classification, our use of synteny is a practical application in a system that has only one parental genome available.

scholarly journals Comparative Genomic Analyses Reveal a Specific Mutation Pattern Between Human Coronavirus SARS-CoV-2 and Bat-CoV RaTG13

2020 ◽  
Vol 11 ◽  
Author(s):  
Longxian Lv ◽  
Gaolei Li ◽  
Jinhui Chen ◽  
Xinle Liang ◽  
Yudong Li
Keyword(s):  
Relative Proportion ◽  
Synonymous Substitution ◽  
Comparative Genomic ◽  
Nucleotide Substitutions ◽  
Spike Gene ◽  
Synonymous Mutations ◽  
Global Pandemic ◽  
Genomic Analyses ◽  
Synonymous Substitution Rates ◽  
Mutation Pattern

BackgroundThe outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, rapidly grew into a global pandemic. How SARS-CoV-2 evolved remains unclear.MethodsWe performed a comprehensive analysis using the available genomes of SARS-CoV-2 and its closely related coronaviruses.ResultsThe ratio of nucleotide substitutions to amino acid substitutions of the spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-CoV RaTG13 was markedly higher than that between other coronaviruses (range, 1.29–4.81); the ratio of non-synonymous to synonymous substitution rates (dN/dS) between SARS-CoV-2 WIV04 and Bat-CoV RaTG13 was the lowest among all the performed comparisons, suggesting evolution under stringent selective pressure. Notably, the relative proportion of the T:C transition was markedly higher between SARS-CoV-2 WIV04 and Bat-CoV RaTG13 than between other compared coronaviruses. Codon usage is similar across these coronaviruses and is unlikely to explain the increased number of synonymous mutations. Moreover, some sites of the spike protein might be subjected to positive selection.ConclusionsOur results showed an increased proportion of synonymous substitutions and the T:C transition between SARS-CoV-2 and RaTG13. Further investigation of the mutation pattern mechanism would contribute to understanding viral pathogenicity and its adaptation to hosts.

scholarly journals Circumsporozoite protein genes of malaria parasites (Plasmodium spp.): evidence for positive selection on immunogenic regions.

Genetics ◽  
1991 ◽  
Vol 127 (2) ◽  
pp. 345-353 ◽  
Author(s):  
A L Hughes
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Positive Selection ◽  
Dna Sequences ◽  
Synonymous Substitution ◽  
T Cell Epitopes ◽  
Repeat Region ◽  
Nucleotide Substitutions ◽  
Malaria Parasites ◽  
Mhc Molecules

Abstract The circumsporozoite (CS) protein is a cell surface protein of the sporozoite, the stage of the life cycle of malaria parasites (Plasmodium spp.) that infects the vertebrate host. Analysis of DNA sequences supports the hypothesis that in Plasmodium falciparum, positive Darwinian selection favors diversity in the T-cell epitopes (peptides presented to T cells by host MHC molecules) of the CS protein. In gene regions encoding T cell epitopes of P. falciparum, the rate of nonsynonymous nucleotide substitution is significantly higher than that of synonymous substitution, whereas this is not true of other gene regions. Furthermore nonsynonymous nucleotide substitutions in these regions cause a change of amino acid residue charge significantly more frequently than expected by chance. By contrast, in Plasmodium cynomolgi, the same regions show no evidence of positive selection, and residue charge is conserved. The CS protein has a central repeat region, which is the target of host antibodies. In P. falciparum, the amino acid sequence of the repeat region is conserved within and between alleles. In P. cynomolgi, on the other hand, there is evidence that positive selection has favored evolution of two different repeat types within a given allele.

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