Biology subjects

Liachko, I.

Publications and source records attributed to Liachko, I..

4 recordsLinked to original sources

bioRxiv2018

Repeat elements organize 3D genome structure and mediate transcription in the filamentous fungus Epichloë festucae

Structural features of genomes, including the three-dimensional arrangement of DNA in the nucleus, are increasingly seen as key contributors to the regulation of gene expression. However, studies on how genome structure and nuclear organization influence transcription have so far been limited to a handful of model species. This narrow focus limits our ability to draw general conclusions about the ways in which three-dimensional structures are encoded, and to integrate information from three-dimensional data to address a broader gamut of biological questions. Here, we generate a complete and gapless genome sequence for the filamentous fungus, Epichloe festucae. Coupling it with RNAseq and HiC data, we investigate how the structure of the genome contributes to the suite of transcriptional changes that an Epichloe species needs to maintain symbiotic relationships with its grass host. Our results reveal a unique \"patchwork\" genome, in which repeat-rich blocks of DNA with discrete boundaries are interspersed by gene-rich sequences. In contrast to other species, the three-dimensional structure of the genome is anchored by these repeat blocks, which act to isolate transcription in neighbouring gene-rich regions. Genes that are differentially expressed in planta are enriched near the boundaries of these repeat-rich blocks, suggesting that their three-dimensional orientation partly encodes and regulates the symbiotic relationship formed by this organism.

genomics↗

bioRxiv2017

Hi-C deconvolution of a human gut microbiome yields high-quality draft genomes and reveals plasmid-genome interactions.

The assembly of high-quality genomes from mixed microbial samples is a long-standing challenge in genomics and metagenomics. Here, we describe the application of ProxiMeta, a Hi-C-based metagenomic deconvolution method, to deconvolve a human fecal metagenome. This method uses the intra-cellular proximity signal captured by Hi-C as a direct indicator of which sequences originated in the same cell, enabling culture-free de novo deconvolution of mixed genomes without any reliance on a priori information. We show that ProxiMeta deconvolution provides results of markedly high accuracy and sensitivity, yielding 50 near-complete microbial genomes (many of which are novel) from a single fecal sample, out of 252 total genome clusters. ProxiMeta outperforms traditional contig binning at high-quality genome reconstruction. ProxiMeta shows particularly good performance in constructing high-quality genomes for diverse but poorly-characterized members of the human gut. We further use ProxiMeta to reconstruct genome plasmid content and sharing of plasmids among genomes--tasks that traditional binning methods usually fail to accomplish. Our findings suggest that Hi-C-based deconvolution can be useful to a variety of applications in genomics and metagenomics.

genomics↗

bioRxiv2017

Identification of a novel interspecific hybrid yeast from a metagenomic open fermentation sample using Hi-C

Interspecific hybridization is a common mechanism enabling genetic diversification and adaptation; however, the detection of hybrid species has been quite difficult. The identification of microbial hybrids is made even more complicated, as most environmental microbes are resistant to culturing and must be studied in their native mixed communities. We have previously adapted the chromosome conformation capture method Hi-C to the assembly of genomes from mixed populations. Here, we show the methods application in assembling genomes directly from an uncultured, mixed population from a spontaneously inoculated beer sample. Our assembly method has enabled us to de-convolute 4 bacterial and 4 yeast genomes from this sample, including a putative yeast hybrid. Downstream isolation and analysis of this hybrid confirmed its genome to consist of Pichia membranifaciens and that of another related, but undescribed yeast. Our work shows that Hi-C-based metagenomic methods can overcome the limitation of traditional sequencing methods in studying complex mixtures of genomes.

genomics↗

bioRxiv2016

The dynamic three-dimensional organization of the diploid yeast genome

The budding yeast Saccharomyces cerevisiae is a long-standing model for the three-dimensional organization of eukaryotic genomes. Even in this well-studied model, it is unclear how homolog pairing in diploids and environment-induced gene relocalization influence overall genome organization. Here, we performed high-throughput chromosome conformation capture on diverged Saccharomyces hybrid diploids to obtain the first global view of chromosome conformation in diploid yeasts. After controlling for the Rabl-like orientation, we observe significant homolog proximity that increased in saturated culture conditions. Surprisingly, we observe a localized increase in homologous interactions between the HAS1 alleles specifically under galactose induction and saturated growth, mediated by association with nuclear pore complexes at the nuclear periphery. Together, these results reveal that the diploid yeast genome has a dynamic and complex 3D organization.

genomics↗