Biology subjects

Kristiansen, K.

Publications and source records attributed to Kristiansen, K..

8 recordsLinked to original sources

bioRxiv2018

The population history of northeastern Siberia since the Pleistocene

Far northeastern Siberia has been occupied by humans for more than 40 thousand years. Yet, owing to a scarcity of early archaeological sites and human remains, its population history and relationship to ancient and modern populations across Eurasia and the Americas are poorly understood. Here, we analyze 34 ancient genome sequences, including two from fragmented milk teeth found at the ~31.6 thousand-year-old (kya) Yana RHS site, the earliest and northernmost Pleistocene human remains found. These genomes reveal complex patterns of past population admixture and replacement events throughout northeastern Siberia, with evidence for at least three large-scale human migrations into the region. The first inhabitants, a previously unknown population of \"Ancient North Siberians\" (ANS), represented by Yana RHS, diverged ~38 kya from Western Eurasians, soon after the latter split from East Asians. Between 20 and 11 kya, the ANS population was largely replaced by peoples with ancestry related to present-day East Asians, giving rise to ancestral Native Americans and \"Ancient Paleosiberians\" (AP), represented by a 9.8 kya skeleton from Kolyma River. AP are closely related to the Siberian ancestors of Native Americans, and ancestral to contemporary communities such as Koryaks and Itelmen. Paleoclimatic modelling shows evidence for a refuge during the last glacial maximum (LGM) in southeastern Beringia, suggesting Beringia as a possible location for the admixture forming both ancestral Native Americans and AP. Between 11 and 4 kya, AP were in turn largely replaced by another group of peoples with ancestry from East Asia, the \"Neosiberians\" from which many contemporary Siberians derive. We detect gene flow events in both directions across the Bering Strait during this time, influencing the genetic composition of Inuit, as well as Na Dene-speaking Northern Native Americans, whose Siberian-related ancestry components is closely related to AP. Our analyses reveal that the population history of northeastern Siberia was highly dynamic throughout the Late Pleistocene and Holocene. The pattern observed in northeastern Siberia, with earlier, once widespread populations being replaced by distinct peoples, seems to have taken place across northern Eurasia, as far west as Scandinavia.

genomics↗

bioRxiv2018

MetaPGN: a pipeline for construction and graphical visualization of annotated pangenome networks

Pangenome analyses facilitate the interpretation of genetic diversity and evolutionary history of a taxon. However, there is an urgent and unmet need to develop new tools for advanced pangenome construction and visualization, especially for metagenomic data. Here we present an integrated pipeline, named MetaPGN, for construction and graphical visualization of pangenome network from either microbial genomes or metagenomes. Given either isolated genomes or metagenomic assemblies coupled with a reference genome of the targeted taxon, MetaPGN generates a pangenome in a topological network, consisting of genes (nodes) and gene-gene genomic adjacencies (edges) of which biological information can be easily updated and retrieved. MetaPGN also includes a self-developed Cytoscape plugin for layout of and interaction with the resulting pangenome network, providing an intuitive and interactive interface for full exploration of genetic diversity. We demonstrate the utility of MetaPGN by constructing Escherichia coli (E. coli) pangenome networks from five E. coli pathogenic strains and 760 human gut microbiomes respectively, revealing extensive genetic diversity of E. coli within both isolates and gut microbial populations. With the ability to extract and visualize gene contents and gene-gene physical adjacencies of a specific taxon from large-scale metagenomic data, MetaPGN provides advantages in expanding pangenome analysis to uncultured microbial taxa. MetaPGN is available at https://github.com/peng-ye/MetaPGN.

genomics↗

bioRxiv2018

Single-cell RNA-seq reveals distinct dynamic behavior of sex chromosomes during early human embryogenesis

AbstractO_ST_ABSBackgroundC_ST_ABSSeveral animal and human studies have demonstrated that sex affects kinetics and metabolism during early embryo development. However, the mechanism governing these differences at the molecular level is unknown, warranting a systematic profiling of gene expression in males and females during embryogenesis.\n\nFindingsWe performed comprehensive analyses of gene expression comparing male and female embryos using available single-cell RNA-sequencing data of 1607 individual cells from 99 human preimplantation embryos, covering development stages from 4-cell to late blastocyst (E2 to E7). Consistent chromosome-wide transcription of autosomes was observed, while sex chromosomes showed significant differences after embryonic genome activation (EGA). Differentially expressed genes (DE genes) in male and female embryos mainly involved in the cell cycle, protein translation and metabolism. The Y chromosome was initially activated by pioneer genes, RPS4Y1 and DDX3Y, while the two X chromosomes in female were widely activated after EGA. Expression of X-linked genes in female significantly declined at the late blastocyst stage, especially in trophectoderm cells, revealing a rapid process of dosage compensation.\n\nConclusionsWe observed imbalanced expression from sex chromosomes in male and female embryos during EGA, with dosage compensation occurring first in female trophectoderm cells. Studying the effect of sex differences during human embryogenesis, as well as understanding the mechanism of X chromosome inactivation and its correlation with early miscarriage, will provide a basis for advancing assisted reproductive technology (ART) and thereby improve the treatment of infertility and possibly enhance reproductive health.

developmental biology↗

bioRxiv2018

Comprehensive analysis of immune evasion in breast cancer by single-cell RNA-seq

The tumor microenvironment is composed of numerous cell types, including tumor, immune and stromal cells. Cancer cells interact with the tumor microenvironment to suppress anticancer immunity. In this study, we molecularly dissected the tumor microenvironment of breast cancer by single-cell RNA-seq. We profiled the breast cancer tumor microenvironment by analyzing the single-cell transcriptomes of 52,163 cells from the tumor tissues of 15 breast cancer patients. The tumor cells and immune cells from individual patients were analyzed simultaneously at the single-cell level. This study explores the diversity of the cell types in the tumor microenvironment and provides information on the mechanisms of escape from clearance by immune cells in breast cancer.\n\nOne Sentence SummaryLandscape of tumor cells and immune cells in breast cancer by single cell RNA-seq

cancer biology↗

bioRxiv2018

The draft genome sequence of mandrill (Mandrillus sphinx)

BackgroundMandrill (Mandrillus sphinx) is a primate species which belong to Old World monkey (Cercopithecidae) family. It is closely related to human, serving as model for some human diseases researches. However, genetic researches and genomic resources of mandrill were limited, especially comparing to other primate species.\n\nFindingsHere we sequenced 284 Gb data, providing 96-fold coverage (considering the estimate genome size of 2.9 Gb), to construct a reference genome for mandrill. The assembled draft genome was 2.79 Gb with contig N50 of 20.48 Kb and scaffold N50 of 3.56 Mb. We annotated the mandrill genome to find 43.83% repeat elements, as well as 21,906 protein coding genes. We found good quality of the draft genome and gene annotation by BUSCO analysis which revealed 98% coverage of the BUSCOs.\n\nConclusionsWe established the first draft genome sequence of mandrill, which is valuable resource for future evolutionary and human diseases studies.

genomics↗

bioRxiv2018

Single tube bead-based DNA co-barcoding for cost effective and accurate sequencing, haplotyping, and assembly

Obtaining accurate sequences from long DNA molecules is very important for genome assembly and other applications. Here we describe single tube long fragment read (stLFR), a technology that enables this a low cost. It is based on adding the same barcode sequence to sub-fragments of the original long DNA molecule (DNA co-barcoding). To achieve this efficiently, stLFR uses the surface of microbeads to create millions of miniaturized barcoding reactions in a single tube. Using a combinatorial process up to 3.6 billion unique barcode sequences were generated on beads, enabling practically non-redundant co-barcoding with 50 million barcodes per sample. Using stLFR, we demonstrate efficient unique co-barcoding of over 8 million 20-300 kb genomic DNA fragments. Analysis of the genome of the human genome NA12878 with stLFR demonstrated high quality variant calling and phasing into contigs up to N50 34 Mb. We also demonstrate detection of complex structural variants and complete diploid de novo assembly of NA12878. These analyses were all performed using single stLFR libraries and their construction did not significantly add to the time or cost of whole genome sequencing (WGS) library preparation. stLFR represents an easily automatable solution that enables high quality sequencing, phasing, SV detection, scaffolding, cost-effective diploid de novo genome assembly, and other long DNA sequencing applications.

genomics↗

bioRxiv2018

A catalog of microbial genes from the bovine rumen reveals the determinants of herbivory

BackgroundThe rumen microbiota provides essential services to its host and, through its role in ruminant production, contributes to human nutrition and food security. A thorough knowledge of the genetic potential of rumen microbes will provide opportunities for improving the sustainability of ruminant production systems. The availability of gene reference catalogs from gut microbiomes has advanced the understanding of the role of the microbiota in health and disease in humans and other mammals. In this work, we established a catalog of reference prokaryote genes from the bovine rumen.\n\nResultsUsing deep metagenome sequencing we identified 13,825,880 non-redundant prokaryote genes from the bovine rumen. Compared to human, pig and mouse gut metagenome catalogs, the rumen is larger and richer in functions and microbial species associated with the degradation of plant cell wall material and production of methane. Genes encoding enzymes catalyzing the breakdown of plant polysaccharides showed a particularly high richness that is otherwise impossible to infer from available genomes or shallow metagenomics sequencing. The catalog expands by several folds the dataset of carbohydrate-degrading enzymes described in the rumen. Using an independent dataset from a group of 77 cattle fed 4 common dietary regimes, we found that only <0.1% of genes were shared by all animals, which contrast with a large overlap for functions, i.e. 63% for KEGG functions. Different diets induced differences in the relative abundance rather than the presence or absence of genes explaining the great adaptability of cattle to rapidly adjust to dietary changes.\n\nConclusionsThese data bring new insights into functions, carbohydrate-degrading enzymes and microbes of the rumen that is complementing the available information on microbial genomes. The catalog is a significant biological resource enabling deeper understanding of phenotypes and biological processes and will be expanded as new data is made available.

microbiology↗

bioRxiv2017

The Beaker Phenomenon And The Genomic Transformation Of Northwest Europe

Bell Beaker pottery spread across western and central Europe beginning around 2750 BCE before disappearing between 2200-1800 BCE. The mechanism of its expansion is a topic of long-standing debate, with support for both cultural diffusion and human migration. We present new genome-wide ancient DNA data from 170 Neolithic, Copper Age and Bronze Age Europeans, including 100 Beaker-associated individuals. In contrast to the Corded Ware Complex, which has previously been identified as arriving in central Europe following migration from the east, we observe limited genetic affinity between Iberian and central European Beaker Complex-associated individuals, and thus exclude migration as a significant mechanism of spread between these two regions. However, human migration did have an important role in the further dissemination of the Beaker Complex, which we document most clearly in Britain using data from 80 newly reported individuals dating to 3900-1200 BCE. British Neolithic farmers were genetically similar to contemporary populations in continental Europe and in particular to Neolithic Iberians, suggesting that a portion of the farmer ancestry in Britain came from the Mediterranean rather than the Danubian route of farming expansion. Beginning with the Beaker period, and continuing through the Bronze Age, all British individuals harboured high proportions of Steppe ancestry and were genetically closely related to Beaker-associated individuals from the Lower Rhine area. We use these observations to show that the spread of the Beaker Complex to Britain was mediated by migration from the continent that replaced >90% of Britains Neolithic gene pool within a few hundred years, continuing the process that brought Steppe ancestry into central and northern Europe 400 years earlier.

genomics↗