Identification of Natural CRISPR Systems and Targets in the Human Microbiome

Münch, Philipp; Franzosa, Eric A.; Stecher, Bärbel; McHardy, Alice C.; Huttenhower, Curtis

doi:10.1016/j.chom.2020.10.010

Cited by 27 publications

(32 citation statements)

References 88 publications

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“…Despite recent studies suggesting that CRISPR-Cas abundance varies across natural environments, such as soil 14 and the human microbiome, 15 the ecological factors that drive variation in CRISPR-Cas prevalence across natural microbial communities remained unclear. 11 Furthermore, the extent of this variation across a much wider range of environments remained unexplored.…”

Section: Resultsmentioning

confidence: 99%

High viral abundance and low diversity are associated with increased CRISPR-Cas prevalence across microbial ecosystems

et al. 2022

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Summary CRISPR-Cas are adaptive immune systems that protect their hosts against viruses and other parasitic mobile genetic elements. 1 Although widely distributed among prokaryotic taxa, CRISPR-Cas systems are not ubiquitous. 2 , 3 , 4 Like most defense-system genes, CRISPR-Cas are frequently lost and gained, suggesting advantages are specific to particular environmental conditions. 5 Selection from viruses is assumed to drive the acquisition and maintenance of these immune systems in nature, and both theory 6 , 7 , 8 and experiments have identified phage density and diversity as key fitness determinants. 9 , 10 However, these approaches lack the biological complexity inherent in nature. Here, we exploit metagenomic data from 324 samples across diverse ecosystems to analyze CRISPR abundance in natural environments. For each metagenome, we quantified viral abundance and diversity to test whether these contribute to CRISPR-Cas abundance across ecosystems. We find a strong positive association between CRISPR-Cas abundance and viral abundance. In addition, when controlling for differences in viral abundance, CRISPR-Cas systems are more abundant when viral diversity is low, suggesting that such adaptive immune systems may offer limited protection when required to target a diverse viral community. CRISPR-Cas abundance also differed among environments, with environmental classification explaining roughly a quarter of the variation in CRISPR-Cas relative abundance. The relationships between CRISPR-Cas abundance, viral abundance, and viral diversity are broadly consistent across environments, providing robust evidence from natural ecosystems that supports predictions of when CRISPR is beneficial. These results indicate that viral abundance and diversity are major ecological factors that drive the selection and maintenance of CRISPR-Cas in microbial ecosystems.

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Section: Resultsmentioning

confidence: 99%

High viral abundance and low diversity are associated with increased CRISPR-Cas prevalence across microbial ecosystems

et al. 2022

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“…Despite recent studies suggesting that CRISPR-Cas abundance varies across natural environments, such as soil [15] and the human microbiome [16], the ecological factors that drive variation in CRISPR-Cas prevalence across natural microbial communities remained unclear [12]. Furthermore, the extent of this variation across a much wider range of environments remained unexplored.…”

Section: Discussionmentioning

confidence: 99%

“…A higher CRISPR likelihood score cut-off of 4.5 was used instead of the default score cut-off of 3 to reduce potential non-CRISPR arrays. CRISPRDetect [16] uses several CRISPR elements (e.g. repeats, spacers, cas genes, AT composition of flanking regions etc.)…”

Section: Methodsmentioning

confidence: 99%

“…Subsampled reads were then screened against this database using metaCRISPRDetect (https://github.com/ambarishbiswas/metaCRISPRDetect_1.0), which supports rapid identification of CRISPR arrays in short reads using user-provided reference repeat database as an extension of CRISPRDetect [16]. Arrays with a likelihood score > 3 were added to the existing CRISPR reference database.…”

Section: Methodsmentioning

confidence: 99%

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High viral abundance and low diversity are associated with increased CRISPR-Cas prevalence across microbial ecosystems

Meaden

Biswas

Arkhipova

et al. 2021

Preprint

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CRISPR-Cas are adaptive immune systems that protect their hosts against viruses and other parasitic mobile genetic elements. Consequently, selection from viruses and other genetic parasites is often assumed to drive the acquisition and maintenance of these immune systems in nature, but this remains untested. Here, we analyse the abundance of CRISPR arrays in natural environments using metagenomic datasets from 332 terrestrial, aquatic and host-associated ecosystems. For each metagenome we quantified viral abundance and levels of viral community diversity to test whether these variables can explain variation in CRISPR-Cas abundance across ecosystems. We find a strong positive correlation between CRISPR-Cas abundance and viral abundance. In addition, when controlling for differences in viral abundance, we found that the CRISPR-Cas systems are more abundant when viral diversity is low. We also found differences in relative CRISPR-Cas abundance among environments, with environmental classification explaining ∼24% of variation in CRISPR-Cas abundance. However, the correlations with viral abundance and diversity are broadly consistent across diverse natural environments. These results indicate that viral abundance and diversity are major ecological factors that drive the selection and maintenance of CRISPR-Cas in microbial ecosystems.Significance statementNumerous studies demonstrate that CRISPR-Cas immune systems can provide defence against bacteriophage and archaeal viruses, yet little is known about the ecological conditions where CRISPR-Cas immunity is favoured. Moreover, our knowledge is largely confined to laboratory studies and it is unknown if viruses are a key selective driver of CRISPR-Cas in nature. Using metagenomic data from diverse environments we find that both viral abundance and the abundance of CRISPR-Cas immune systems correlate positively across most environments. Furthermore, CRISPR-Cas systems are more prevalent when viral diversity is low. These results extend previous theoretical work by demonstrating that viruses are a key driver of selection of CRISPR-Cas immune systems across many natural ecosystems.

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“…Several studies were conducted from the description of systems in different ecological niches (e.g., [36]) to targeted search for new systems with editing potential (e.g., [37]). Human microbiome was not set aside here as well, being studied with different approaches for arrays' identification and analysis (e.g., [38,39]). In all these studies an emphasis was made on the natural CRISPR-Cas systems in healthy human microbiomes.…”

Section: Introductionmentioning

confidence: 99%

CRISPR-Cas Systems in Gut Microbiome of Children with Autism Spectrum Disorders

Zakharevich¹,

Nikitin²,

Kovtun³

et al. 2022

Preprint

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Human gut microbiome is associated with various diseases, including autism spectrum disorders (ASD). Variations of the taxonomical composition in the gut microbiome of children with ASD have been observed repeatedly. However, features and parameters of the CRISPR-Cas systems in the gut microbiome of children with ASD have not been investigated yet. Here we demonstrate such an analysis in comparison with the healthy microbiome. For the identification of CRISPR-Cas systems, we used a combination of the publicly available tools suited for completed genomes with subsequent filtrations. In all considered datasets, the microbiomes of children with ASD contained fewer arrays per Gb of assembly, than the control group, but the arrays included more spacers on average. These patterns were observed systematically in our datasets, although their statistical significance hardly matched the thresholds. CRISPR arrays from the microbiomes of children with ASD differed from the control group neither in the fractions of spacers with protospacers from known genomes, nor in the sets of known bacteriophages providing protospacers. The majority of bacterial protospacers of the gut microbiome systems for both children with ASD and the healthy ones was located in the prophage islands.

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Identification of Natural CRISPR Systems and Targets in the Human Microbiome

Cited by 27 publications

References 88 publications

High viral abundance and low diversity are associated with increased CRISPR-Cas prevalence across microbial ecosystems

High viral abundance and low diversity are associated with increased CRISPR-Cas prevalence across microbial ecosystems

High viral abundance and low diversity are associated with increased CRISPR-Cas prevalence across microbial ecosystems

CRISPR-Cas Systems in Gut Microbiome of Children with Autism Spectrum Disorders

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