scholarly journals Unexpected diversity of CRISPR unveils some evolutionary patterns of repeated sequences in Mycobacterium tuberculosis

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Guislaine Refrégier ◽  
Christophe Sola ◽  
Christophe Guyeux
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Insertion Sequence ◽  
Recent Common Ancestor ◽  
Direct Repeats ◽  
Evolutionary Mechanisms ◽  
Evolutionary Patterns ◽  
Crispr Locus ◽  
Most Recent Common Ancestor ◽  
Low Diversity ◽  
Set Up

Abstract Background Diversity of the CRISPR locus of Mycobacterium tuberculosis complex has been studied since 1997 for molecular epidemiology purposes. By targeting solely the 43 spacers present in the two first sequenced genomes (H37Rv and BCG), it gave a biased idea of CRISPR diversity and ignored diversity in the neighbouring cas-genes. Results We set up tailored pipelines to explore the diversity of CRISPR-cas locus in Short Reads. We analyzed data from a representative set of 198 clinical isolates as evidenced by well-characterized SNPs. We found a relatively low diversity in terms of spacers: we recovered only the 68 spacers that had been described in 2000. We found no partial or global inversions in the sequences, letting always the Direct Variant Repeats (DVR) in the same order. In contrast, we found an unexpected diversity in the form of: SNPs in spacers and in Direct Repeats, duplications of various length, and insertions at various locations of the IS6110 insertion sequence, as well as blocks of DVR deletions. The diversity was in part specific to lineages. When reconstructing evolutionary steps of the locus, we found no evidence for SNP reversal. DVR deletions were linked to recombination between IS6110 insertions or between Direct Repeats. Conclusion This work definitively shows that CRISPR locus of M. tuberculosis did not evolve by classical CRISPR adaptation (incorporation of new spacers) since the last most recent common ancestor of virulent lineages. The evolutionary mechanisms that we discovered could be involved in bacterial adaptation but in a way that remains to be identified.

scholarly journals Unexpected diversity of CRISPR unveils some evolutionary patterns of repeated sequences in Mycobacterium tuberculosis

2019 ◽  
Author(s):  
Guislaine Refrégier ◽  
Christophe Sola ◽  
Christophe Guyeux
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Insertion Sequence ◽  
Recent Common Ancestor ◽  
Direct Repeats ◽  
Evolutionary Mechanisms ◽  
Evolutionary Patterns ◽  
Crispr Locus ◽  
Most Recent Common Ancestor ◽  
Low Diversity ◽  
Set Up

AbstractDiversity of the CRISPR locus of Mycobacterium tuberculosis complex has been studied since 1997 for molecular epidemiology purposes. By targeting solely the 43 spacers present in the two first sequenced genomes (H37Rv and BCG), it gave a biased idea of CRISPR diversity and ignored diversity in the neighbouring cas-genes.We set up tailored pipelines to explore the diversity of CRISPR-cas locus in Short Reads. We analyzed data from a representative set of 198 clinical isolates as evidenced by well-characterized SNPs.We found a relatively low diversity in terms of spacers: we recovered only the 68 spacers that had been described in 2000. We found no partial or global inversions in the sequences, letting always the Direct Variant Repeats (DVR) in the same order. In contrast, we found an unexpected diversity in the form of: SNPs in spacers and in Direct Repeats, duplications of various length, and insertions at various locations of the IS6110 insertion sequence, as well as blocks of DVR deletions. The diversity was in part specific to lineages. When reconstructing evolutionary steps of the locus, we found no evidence for SNP reversal. DVR deletions were linked to recombination between IS6110 insertions or between Direct Repeats.This work definitively shows that CRISPR locus of M. tuberculosis did not evolve by classical CRISPR adaptation (incorporation of new spacers) since the last most recent common ancestor of virulent lineages. The evolutionary mechanisms that we discovered could be involved in bacterial adaptation but in a way that remains to be identified.

scholarly journals CRISPRbuilder-TB: “CRISPR-builder for tuberculosis”. Exhaustive reconstruction of the CRISPR locus in mycobacterium tuberculosis complex using SRA

2021 ◽  
Vol 17 (3) ◽  
pp. e1008500
Author(s):  
Christophe Guyeux ◽  
Christophe Sola ◽  
Camille Noûs ◽  
Guislaine Refrégier
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bacterial Species ◽  
Direct Repeats ◽  
Crispr Locus ◽  
The Public ◽  
Whole Process ◽  
General Rules ◽  
Genetic Mechanisms ◽  
Set Up

Mycobacterium tuberculosis complex (MTC) CRISPR locus diversity has long been studied solely investigating the presence/absence of a known set of spacers. Unveiling the genetic mechanisms of its evolution requires a more exhaustive reconstruction in a large amount of representative strains. In this article, we point out and resolve, with a new pipeline, the problem of CRISPR reconstruction based directly on short read sequences in M. tuberculosis. We first show that the process we set up, that we coin as “CRISPRbuilder-TB” (https://github.com/cguyeux/CRISPRbuilder-TB), allows an efficient reconstruction of simulated or real CRISPRs, even when including complex evolutionary steps like the insertions of mobile elements. Compared to more generalist tools, the whole process is much more precise and robust, and requires only minimal manual investigation. Second, we show that more than 1/3 of the currently complete genomes available for this complex in the public databases contain largely erroneous CRISPR loci. Third, we highlight how both the classical experimental in vitro approach and the basic in silico spoligotyping provided by existing analytic tools miss a whole diversity of this locus in MTC, by not capturing duplications, spacer and direct repeats variants, and IS6110 insertion locations. This description is extended in a second article that describes MTC-CRISPR diversity and suggests general rules for its evolution. This work opens perspectives for an in-depth exploration of M. tuberculosis CRISPR loci diversity and of mechanisms involved in its evolution and its functionality, as well as its adaptation to other CRISPR locus-harboring bacterial species.

scholarly journals Population genomics of Mycobacterium tuberculosis in the Inuit

2015 ◽  
Vol 112 (44) ◽  
pp. 13609-13614 ◽  
Author(s):  
Robyn S. Lee ◽  
Nicolas Radomski ◽  
Jean-Francois Proulx ◽  
Ines Levade ◽  
B. Jesse Shapiro ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Mycobacterium Tuberculosis ◽  
Population Genomics ◽  
Purifying Selection ◽  
Synonymous Substitution ◽  
Nonsynonymous Snps ◽  
Recent Common Ancestor ◽  
Nucleotide Polymorphisms ◽  
Most Recent Common Ancestor ◽  
Bacterial Genetic

Nunavik, Québec suffers from epidemic tuberculosis (TB), with an incidence 50-fold higher than the Canadian average. Molecular studies in this region have documented limited bacterial genetic diversity among Mycobacterium tuberculosis isolates, consistent with a founder strain and/or ongoing spread. We have used whole-genome sequencing on 163 M. tuberculosis isolates from 11 geographically isolated villages to provide a high-resolution portrait of bacterial genetic diversity in this setting. All isolates were lineage 4 (Euro-American), with two sublineages present (major, n = 153; minor, n = 10). Among major sublineage isolates, there was a median of 46 pairwise single-nucleotide polymorphisms (SNPs), and the most recent common ancestor (MRCA) was in the early 20th century. Pairs of isolates within a village had significantly fewer SNPs than pairs from different villages (median: 6 vs. 47, P < 0.00005), indicating that most transmission occurs within villages. There was an excess of nonsynonymous SNPs after the diversification of M. tuberculosis within Nunavik: The ratio of nonsynonymous to synonymous substitution rates (dN/dS) was 0.534 before the MRCA but 0.777 subsequently (P = 0.010). Nonsynonymous SNPs were detected across all gene categories, arguing against positive selection and toward genetic drift with relaxation of purifying selection. Supporting the latter possibility, 28 genes were partially or completely deleted since the MRCA, including genes previously reported to be essential for M. tuberculosis growth. Our findings indicate that the epidemiologic success of M. tuberculosis in this region is more likely due to an environment conducive to TB transmission than a particularly well-adapted strain.

scholarly journals A closer look at pupil diversity and evolution in frogs and toads

2021 ◽  
Vol 288 (1957) ◽  
pp. 20211402
Author(s):  
Nadia G. Cervino ◽  
Agustín J. Elias-Costa ◽  
Martín O. Pereyra ◽  
Julián Faivovich
Keyword(s):  
Life Histories ◽  
Activity Patterns ◽  
Diel Activity ◽  
Recent Common Ancestor ◽  
Evolutionary Patterns ◽  
Most Recent Common Ancestor ◽  
Diel Activity Patterns ◽  
History Of ◽  
Ecological Versatility

The eyes of frogs and toads (Anura) are among their most fascinating features. Although several pupil shapes have been described, the diversity, evolution, and functional role of the pupil in anurans have received little attention. Studying photographs of more than 3200 species, we surveyed pupil diversity, described their morphological variation, tested correlation with adult habits and diel activity, and discuss major evolutionary patterns considering iris anatomy and visual ecology. Our results indicate that the pupil in anurans is a highly plastic structure, with seven main pupil shapes that evolved at least 116 times during the history of the group. We found no significant correlation between pupil shape, adult habits, and diel activity, with the exception of the circular pupil and aquatic habits. The vertical pupil arose at least in the most-recent common ancestor of Anura + Caudata, and this morphology is present in most early-diverging anuran clades. Subsequently, a horizontal pupil, a very uncommon shape in vertebrates, evolved in most neobatrachian frogs. This shape evolved into most other known pupil shapes, but it persisted in a large number of species with diverse life histories, habits, and diel activity patterns, demonstrating a remarkable functional and ecological versatility.

scholarly journals Genomic and Micro-Evolutionary Features of Mammalian 2 orthobornavirus (Variegated Squirrel Bornavirus 1, VSBV-1)

2021 ◽  
Vol 9 (6) ◽  
pp. 1141
Author(s):  
Dániel Cadar ◽  
Jonas Schmidt-Chanasit ◽  
Dennis Tappe
Keyword(s):  
Evolutionary Dynamics ◽  
Animal Husbandry ◽  
Purifying Selection ◽  
Recent Common Ancestor ◽  
Positive Pressure ◽  
Evolutionary Mechanisms ◽  
Time Resolved ◽  
Viral Pathogen ◽  
Most Recent Common Ancestor ◽  
Evolutionary Features

Mammalian 2 orthobornavirus (VSBV-1) is an emerging zoonotic pathogen discovered in several exotic squirrel species and associated with fatal human encephalitis. The dynamics of VSBV-1 spread and evolution in its presumed natural hosts are unknown. Here, we present the phylogeny, micro-evolution, cross-species transmission and spread of VSBV-1 at a temporal and spatial resolution within the limits of animal husbandry. The results showed that VSBV-1 can be classified into six distinct groups and that the most recent common ancestor of the known German strains emerged at least 20 years ago. We here demonstrate that the genetic diversity of the VSBV-1 groups is shaped primarily by in situ evolution and most of the amino acid changes are deleterious polymorphisms removed by purifying selection. Evidence of adaptive evolution has been found in the G and L genes which might have an influence on transmission fitness. Furthermore, there was also evidence for some form of adaptive changes in the glycoprotein which suggests that many sites might be subjected to positive pressure evolving under episodic directional selection, indicating past occurrence of positive selection. Host switching events were detected as dominant evolutionary mechanisms driving the virus-host associations. Virus spread by animal trade followed by subsequent local micro-evolution in zoos and holdings is responsible for diversifying strains. Time-resolved phylogeny indicated that Prevost’s squirrels might be the original squirrel species carrying and seeding the virus in Germany. This study provides the first insight into the ecology and micro-evolutionary dynamics of this novel viral pathogen in the captive exotic squirrel population under artificial ecological conditions (zoos and animal husbandry) and co-housing of different squirrel species.

scholarly journals On the contingent nature of satellite DNA evolution

2021 ◽  
Author(s):  
Juan Pedro M Camacho ◽  
Josefa Cabrero ◽  
Maria Dolores Lopez-Leon ◽  
Maria Martin-Pecina ◽  
Francisco Perfectti ◽  
...  
Keyword(s):  
Concerted Evolution ◽  
Satellite Dna ◽  
Common Ancestor ◽  
Locusta Migratoria ◽  
Recent Common Ancestor ◽  
Evolutionary Mechanisms ◽  
Consensus Sequences ◽  
Most Recent Common Ancestor ◽  
Dna Conformations ◽  
Library Hypothesis

Background: The full catalogue of satellite DNA (satDNA) within a same genome constitutes the satellitome. The Library Hypothesis predicts that satDNA in relative species reflects that in their common ancestor, but the evolutionary mechanisms and pathways of satDNA evolution have never been analyzed for full satellitomes. We compare here the satellitomes of two Oedipodine grasshoppers (Locusta migratoria and Oedaleus decorus) which shared their most recent common ancestor about 22.8 Ma ago. Results: We found that about one-third of their satDNA families (near 60 in every species) showed sequence homology, and were grouped into 12 orthologous superfamilies. The turnover rate of consensus sequences was extremely variable among the 20 orthologous family pairs analyzed in both species. The satDNAs shared by both species showed poor association with sequence signatures and motives frequently argued as functional, except for short inverted repeats allowing short dyad symmetries and non-B DNA conformations. Orthologous satDNAs frequently showed different FISH pattern at both intra- and interspecific levels. We defined indices of homogenization and degeneration, and quantified the level of incomplete library sorting between species. Conclusions: Our analyses revealed that satDNA degenerates through point mutation and rejuvenates through partial turnovers caused by massive tandem duplications (the so-called satDNA amplification). Remarkably, satDNA amplification increases homogenization, at intragenomic level, and diversification between species, thus constituting the basis for concerted evolution. We suggest a model of satDNA evolution by means of recursive cycles of amplification, degeneration, and rejuvenation, leading to mostly contingent evolutionary pathways where concerted evolution emerges promptly after lineages split.

Spread of Mycobacterium Tuberculosis Lineage 4 in Sichuan-chongqing Region of China Influenced by Maritime Silk Road and “huguang Filling Sichuan” 

2020 ◽  
Author(s):  
Wei Wu ◽  
Peng-kuan Liang ◽  
Hai-Bing Yuan ◽  
Yu-Ang Tian ◽  
Qun Sun
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Geographical Distribution ◽  
National Level ◽  
Silk Road ◽  
Human Migration ◽  
Recent Common Ancestor ◽  
13Th Century ◽  
Most Recent Common Ancestor ◽  
Maritime Silk Road ◽  
Other World

Abstract BackgroundThe spread of Mycobacterium tuberculosis complex (MTBC) was closely influenced by human migration. Lineage 4, a lineage of MTBC mainly being epidemic in Europe and America, was not the major one in China. Its proportion in Sichuan-Chongqing region, however, was significantly higher than that at the national level. Previous study by the most recent common ancestor calculation based on Bayes model suggested that lineage 4 epidemic in South China today probably entered China around the 13th century, and the most important human migration events associating with this region during and after this period of time included Maritime Silk Road and “Huguang filling Sichuan”. The purpose of this study was to explore whether the high proportion of lineage 4 in Sichuan-Chongqing region was impacted by these two events. MethodsThe genotyping data of 17,269 MTBC isolates, the proportion of targeted surname populations related to “Huguang filling Sichuan”, and the information of main ports’ location around Maritime Silk Road were collected. Interpolation analysis was used to estimate the geographical distribution of lineage 4 and its three sub-lineages (L4.2, L4.4, L4,5), as well as the targeted surname populations. And the correlation between the geographical distribution in the main ports on Maritime Silk Road and the regions with the proportion of L4.2 and L4.4 was analyzed.ResultsInterpolation and correlation analysis showed that lineage 4’s distribution in China could be mapped to the regions affected by “Huguang filling Sichuan”, while L4.2 and L4.4’s distributing in Asia, Europe, and Africa could be those by Maritime Silk Road, ConclusionsMaritime Silk Road and “Huguang Filling Sichuan” potentially posed an essential combined influence on the greater occurring of lineage 4 in Sichuan-Chongqing region. This study may contribute to the tracing and epidemiological investigation of tuberculosis and other world-wide infectious diseases.

scholarly journals Prisoner of War dynamics explains the time-dependent pattern of substitution rates in viruses

2021 ◽  
Author(s):  
Mahan Ghafari ◽  
Peter Simmonds ◽  
Oliver G Pybus ◽  
Aris Katzourakis
Keyword(s):  
Power Law ◽  
Mechanistic Model ◽  
Evolutionary Rates ◽  
Time Dependent ◽  
Recent Common Ancestor ◽  
Evolutionary Mechanisms ◽  
Substitution Rates ◽  
Most Recent Common Ancestor ◽  
Wide Range ◽  
Rate Decay

AbstractMolecular clock dating is widely used to estimate timescales of phylogenetic histories and to infer rates at which species evolve. One of the major challenges with inferring rates of molecular evolution is the observation of a strong correlation between estimated rates and the timeframe of their measurements. Recent empirical analysis of virus evolutionary rates suggest that a power-law rate decay best explains the time-dependent pattern of substitution rates and that the same pattern is observed regardless of virus type (e.g. groups I-VII in the Baltimore classification). However there exists no explanation for this trend based on molecular evolutionary mechanisms. We provide a simple predictive mechanistic model of the time-dependent rate phenomenon, incorporating saturation and host constraints on the evolution of some sites. Our model recapitulates the ubiquitous power-law rate decay with a slope of −0.65 (95% HPD: −0.72, −0.52) and can satisfactorily account for the variation in inferred molecular evolutionary rates over a wide range of timeframes. We show that once the saturation of sites starts - typically after hundreds of years in RNA viruses and thousands of years in DNA viruses - standard substitution models fail to correctly estimate divergence times among species, while our model successfully re-creates the observed pattern of rate decay. We apply our model to re-date the diversification of genotypes of hepatitis C virus (HCV) to 396,000 (95% HPD: 326,000 - 425,000) years before present, a time preceding the dispersal of modern humans out of Africa, and also showed that the most recent common ancestor of sarbecoviruses dates back to 23,500 (95% HPD: 21,100 - 25,300) years ago, nearly thirty times older than previous estimates. This not only creates a radical new perspective for our understanding the origins of HCV but also suggests a substantial revision of evolutionary timescales of other viruses can be similarly achieved.

scholarly journals Exhaustive reconstruction of the CRISPR locus in Mycobacterium tuberculosis complex using short reads

2019 ◽  
Author(s):  
Christophe Guyeux ◽  
Christophe Sola ◽  
Guislaine Refrégier
Keyword(s):  
Mycobacterium Tuberculosis ◽  
In Silico ◽  
Structural Characteristics ◽  
Computational Method ◽  
Direct Repeats ◽  
Crispr Locus ◽  
Short Read ◽  
General Rules ◽  
Genetic Mechanisms

AbstractSpoligotyping, a graphical partial display of the CRISPR locus that can be produced in vitro or in silico, is an important tool for analyzing the diversity of given Mycobacterium tuberculosis complex (MTC) isolates. As other CRISPR loci, this locus is made up of an alternation between direct repeats and spacers, and flanked by cas genes. Unveiling the genetic mechanisms of its evolution requires to have a fairly large amount of fully reconstructed loci among all MTC lineages.In this article, we point out and resolve the problem of CRISPR reconstruction based on short read sequences. We first show that more than 1/3 of the currently assembled genomes available for this complex contain a CRISPR locus erroneously reconstructed, and errors can be very significant. Second, we present a new computational method allowing this locus to be reconstructed extensively and reliably in silico using short read sequencing runs. Third, using this method, we describe new structural characteristics of CRISPR locus by lineages. We show how both the classical experimental in vitro approach and the basic in silico spoligotyping provided by existing analytic tools miss a whole diversity of this locus in MTC, by not capturing duplications, spacer and direct repeats variants, and IS6110 insertion locations. This description is extended in a second article that presents general rules for the evolution of the CRISPR locus in MTC.This work opens new perspectives for a larger exploration of CRISPR loci diversity and of mechanisms involved in its evolution and its functionality.

scholarly journals Allelic Genealogies in Sporophytic Self-Incompatibility Systems in Plants

Genetics ◽  
1998 ◽  
Vol 150 (3) ◽  
pp. 1187-1198 ◽  
Author(s):  
Mikkel H Schierup ◽  
Xavier Vekemans ◽  
Freddy B Christiansen
Keyword(s):  
Dominance Hierarchy ◽  
Common Ancestor ◽  
Recent Common Ancestor ◽  
Self Incompatibility ◽  
Most Recent Common Ancestor ◽  
Dominance Interactions ◽  
Turnover Process ◽  
Neutral Gene ◽  
Interspecific Comparisons ◽  
Coalescence Times

Abstract Expectations for the time scale and structure of allelic genealogies in finite populations are formed under three models of sporophytic self-incompatibility. The models differ in the dominance interactions among the alleles that determine the self-incompatibility phenotype: In the SSIcod model, alleles act codominantly in both pollen and style, in the SSIdom model, alleles form a dominance hierarchy, and in SSIdomcod, alleles are codominant in the style and show a dominance hierarchy in the pollen. Coalescence times of alleles rarely differ more than threefold from those under gametophytic self-incompatibility, and transspecific polymorphism is therefore expected to be equally common. The previously reported directional turnover process of alleles in the SSIdomcod model results in coalescence times lower and substitution rates higher than those in the other models. The SSIdom model assumes strong asymmetries in allelic action, and the most recessive extant allele is likely to be the most recent common ancestor. Despite these asymmetries, the expected shape of the allele genealogies does not deviate markedly from the shape of a neutral gene genealogy. The application of the results to sequence surveys of alleles, including interspecific comparisons, is discussed.

Sign in / Sign up

Export Citation Format

Share Document