Tracking strains predicts personal microbiomes and reveals recent adaptive evolution

Zhao, Shijie; Dai, Chengkai; Evans, Ethan D.; Lu, Ziyu; Alm, Eric J.

doi:10.1101/2020.09.14.296970

Cited by 6 publications

(3 citation statements)

References 30 publications

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“…As time progresses and purifying selection continuously operates, the d N /d S ratio decreases [14] [19] [22]. However, multiple studies have observed genome-wide values of d N /d S above 1 in these same microbial systems, with values substantially above 1 in key genes, which are simply unaccounted for in the purifying model [19] [20] [23] [24] [25].…”

Section: Introductionmentioning

confidence: 99%

Reversions mask the contribution of adaptive evolution in microbiomes

Torrillo,

Lieberman

2023

Preprint

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When examining bacterial genomes for evidence of past selection, the results obtained depend heavily on the mutational distance between chosen genomes. Even within a bacterial species, genomes separated by larger mutational distances exhibit stronger evidence of purifying selection as assessed by dN/dS, the normalized ratio of nonsynonymous to synonymous mutations. This dependence on mutational distance, and thus time, has been proposed to arise from the inefficiency of purifying selection at removing weakly deleterious mutations. Here, we revisit this assumption in light of abundant genomes from gut microbiomes and show that a model of weak purifying selection that fits the data leads to problematic mutation accumulation. We propose an alternative model to explain the timescale dependence of dN/dS, in which constantly changing environmental pressures select for revertants of previously adaptive mutations. Reversions that sweep within-host populations are nearly guaranteed in microbiomes due to large population sizes, short generation times, and variable environments. Using analytical and simulation approaches, we fit the adaptive reversion model to dN/dS decay curves and obtain estimates of local adaptation that are realistic in the context of bacterial genomes. These results argue for interpreting low values of dN/dS with caution, as they may emerge even when adaptive sweeps are frequent. This work reframes an old observation in bacterial evolution, illustrates the potential of mutation reversions to shape genomic landscapes over time, and highlights the need for additional research on bacterial genomic evolution on short time scales.

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Section: Introductionmentioning

confidence: 99%

Reversions mask the contribution of adaptive evolution in microbiomes

Torrillo,

Lieberman

2023

Preprint

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“…The gut of nearly every individual is colonized with organisms from the phyla Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria (Qin et al, 2010). Despite the universality of these four core phyla, the gut microbiome harbors extraordinary interpersonal complexity, particular at the strain level (Eckburg et al, 2005;Faith et al, 2020Faith et al, , 2013Olm et al, 2021;Schloss et al, 2014;Zhao et al, 2020). The proximity of gut bacteria to the host presents a unique challenge for the immune system, which must maintain tolerance to the resident microbiota while remaining poised to defend against infectious insults.…”

Section: Introductionmentioning

confidence: 99%

Defining Innate Immune Responses to the Human Gut Microbiota from Phylum to Strain

Spindler

Siu

Mogno

et al. 2021

Preprint

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SUMMARYThe functional potential of the gut microbiota remains largely uncharacterized. Efforts to understand how the immune system responds to commensal organisms have been hindered by the large number of strains that comprise the human gut microbiota. We develop a screening platform to measure innate immune responses towards 277 bacterial strains isolated from the human gut microbiota. We find that innate immune responses to gut derived bacteria are as strong as responses towards pathogenic bacteria, and vary from phylum to strain. Myeloid cells differentially rely upon TLR2 or TLR4 to sense particular taxa, an observation that predicts in vivo function. These innate immune responses can be modeled using combinations of up to 8 TLR agonists. Furthermore, the immunogenicity of strains is stable over time and following transplantation into new humans. Collectively, we demonstrate a powerful high-throughput approach to determine how commensal microorganisms shape innate immune phenotypes.

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“…Improving our fundamental understanding of these behaviors depends on detailed knowledge of the genes and pathways specific to particular microbes ( 22 ); however, elucidating this information can present considerable challenges where taxa are only known at the species level, obscuring strain-level differences. Individual microbes from the same strain from a single microbiome largely share the same genome ( 12 , 23 ); therefore, a substantial improvement in understanding would be provided by high-quality genomes resolved to the strain level from a broad range of microbial taxa within a given community.…”

mentioning

confidence: 99%

High-throughput, single-microbe genomics with strain resolution, applied to a human gut microbiome

Zheng

Zhao

Yin

et al. 2022

Science

Self Cite

140

105

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Characterizing complex microbial communities with single-cell resolution has been a long-standing goal of microbiology. We present Microbe-seq, a high-throughput method that yields the genomes of individual microbes from complex microbial communities. We encapsulate individual microbes in droplets with microfluidics and liberate their DNA, which we then amplify, tag with droplet-specific barcodes, and sequence. We explore the human gut microbiome, sequencing more than 20,000 microbial single-amplified genomes (SAGs) from a single human donor and coassembling genomes of almost 100 bacterial species, including several with multiple subspecies strains. We use these genomes to probe microbial interactions, reconstructing the horizontal gene transfer (HGT) network and observing HGT between 92 species pairs; we also identify a significant in vivo host-phage association between crAssphage and one strain of Bacteroides vulgatus . Microbe-seq contributes high-throughput culture-free capabilities to investigate genomic blueprints of complex microbial communities with single-microbe resolution.

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Tracking strains predicts personal microbiomes and reveals recent adaptive evolution

Cited by 6 publications

References 30 publications

Reversions mask the contribution of adaptive evolution in microbiomes

Reversions mask the contribution of adaptive evolution in microbiomes

Defining Innate Immune Responses to the Human Gut Microbiota from Phylum to Strain

High-throughput, single-microbe genomics with strain resolution, applied to a human gut microbiome

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