In a microbial community, associations between constituent members play an important role in determining the overall structure and function of the community. The human gut microbiome is believed to play an integral role in host health and disease. To understand the nature of bacterial associations at the species level in healthy human gut microbiomes, we analyzed previously published collections of whole-genome shotgun sequence data, totaling over 1.6 Tbp, generated from 606 fecal samples obtained from four different healthy human populations. Using a Random Forest Classifier, we identified 202 signature bacterial species that were prevalent in these populations and whose relative abundances could be used to accurately distinguish between the populations. Bacterial association networks were constructed with these signature species using an approach based on the graphical lasso. Network analysis revealed conserved bacterial associations across populations and a dominance of positive associations over negative associations, with this dominance being driven by associations between species that are closely related either taxonomically or functionally. Bacterial species that form network modules, and species that constitute hubs and bottlenecks, were also identified. Functional analysis using protein families suggests that much of the taxonomic variation across human populations does not foment substantial functional or structural differences.
Background Colorectal cancer is a leading cause of cancer-related deaths worldwide. The human gut microbiome has become an active area of research for understanding the initiation, progression, and treatment of colorectal cancer. Despite multiple studies having found significant alterations in the carriage of specific bacteria within the gut microbiome of colorectal cancer patients, no single bacterium has been unequivocally connected to all cases. Whether alterations in species carriages are the cause or outcome of cancer formation is still unclear, but what is clear is that focus should be placed on understanding changes to the bacterial community structure within the cancer-associated gut microbiome. Results By applying a novel set of analyses on 252 previously published whole-genome shotgun sequenced fecal samples from healthy and late-stage colorectal cancer subjects, we identify taxonomic, functional, and structural changes within the cancer-associated human gut microbiome. Bacterial association networks constructed from these data exhibited widespread differences in the underlying bacterial community structure between healthy and colorectal cancer associated gut microbiomes. Within the cancer-associated ecosystem, bacterial species were found to form associations with other species that are taxonomically and functionally dissimilar to themselves, as well as form modules functionally geared towards potential changes in the tumor-associated ecosystem. Bacterial community profiling of these samples revealed a significant increase in species diversity within the cancer-associated gut microbiome, and an elevated relative abundance of species classified as originating from the oral microbiome including, but not limited to, Fusobacterium nucleatum, Peptostreptococcus stomatis, Gemella morbillorum, and Parvimonas micra. Differential abundance analyses of community functional capabilities revealed an elevation in functions linked to virulence factors and peptide degradation, and a reduction in functions involved in amino-acid biosynthesis within the colorectal cancer gut microbiome. Conclusions We utilize whole-genome shotgun sequenced fecal samples provided from a large cohort of late-stage colorectal cancer and healthy subjects to identify a number of potentially important taxonomic, functional, and structural alterations occurring within the colorectal cancer associated gut microbiome. Our analyses indicate that the cancer-associated ecosystem influences bacterial partner selection in the native microbiota, and we highlight specific oral bacteria and their associations as potentially relevant towards aiding tumor progression.
DNA from the cultivated mushroom, Agaricus bisporus, was cloned into the bacteriophage lambda vector EMBL3 creating a partial genomic library. Ten random clones from the library were used to probe for restriction fragment length polymorphisms (RFLPs). Six of the ten probes detected polymorphisms and were used to demonstrate variation in wild and cultivated strains of the mushroom. These results suggest that RFLPs could form a basis for genetic finger-printing and subsequent strain protection in A. bisporus. In single spore progeny, RFLPs were used to demonstrate normal meiotic segregation and to differentiate between homokaryons and heterokaryons. RFLPs therefore have great potential in the development of the genetics and breeding of this commercially important species.
The prevalence of highly repetitive sequences within the human Y chromosome has led to its incomplete assembly and systematic omission from genomic analyses. Here, we present long-read de novo assemblies of 43 diverse Y-chromosomes, three contiguously assembled including two from deep-rooted African Y lineages. Examination of the full extent of genetic variation between Y chromosomes across 180,000 years of human evolution reveals its remarkable complexity and diversity in size and structure, in contrast with its low level of base substitution variation. The size of the Y chromosome assemblies vary extensively from 45.2 to 84.9 Mbp, with individual repeat arrays showing up to 6.7-fold difference in length across samples. Half of the male-specific euchromatic region is subject to large (up to 5.94 Mbp) inversions with a >2-fold higher recurrence rate compared to the rest of the human genome. The Y centromere, composed of 171 bp α-satellite monomer units, appears to have evolved from tandem arrays of a 36-mer ancestral higher order repeat (HOR), which has been predominantly replaced by a 34-mer HOR, and reveals a pattern of higher sequence variation towards the short-arm side. The Yq12 heterochromatic region is ubiquitously flanked by approximately 649 kbp and 472 kbp inversions that maintain the alternating arrays of DYZ1 and DYZ2 repeat units in between. While the sizes and the distribution of the DYZ1 and DYZ2 arrays vary considerably, primarily due to local expansions and contractions, the copy number ratio between the DYZ1 and DYZ2 monomer repeat units remains consistently close to 1:1. In addition, we have identified on average 65 kbp of novel sequence per Y chromosome. The availability of sequence-resolved Y chromosomes from multiple samples provides a basis for identifying new associations of specific traits with the Y chromosome and garnering novel evolutionary insights.
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