Summary of Genomic Architecture Lectures PDF

Summary of lectures presentations and lecture recordings **Table of Contents** [[1. Basics: Genomic Diversity, Central Dogma, Eukaryotes vs Prokaryotes, de Winde 2]](#basics-genomic-diversity-central-dogma-eukaryotes-vs-prokaryotes-de-winde) [[2. Basics: Structure & Function of DNA & RNA, Verscho...

Summary of lectures presentations and lecture recordings **Table of Contents** [[1. Basics: Genomic Diversity, Central Dogma, Eukaryotes vs Prokaryotes, de Winde 2]](#basics-genomic-diversity-central-dogma-eukaryotes-vs-prokaryotes-de-winde) [[2. Basics: Structure & Function of DNA & RNA, Verschoor 5]](#basics-structure-function-of-dna-rna-verschoor) [[3. Phages: Lytic & Lysogenic cycle, Bacterial Defenses & Co-evolution, Mabrouk 8]](#phages-lytic-lysogenic-cycle-bacterial-defenses-co-evolution-mabrouk) [[4. Bacterial Symbionts: Genomic Size, Drift, HGT & Adaptive "Black Queen" Loss, Rozen 11]](#bacterial-symbionts-genomic-size-drift-hgt-adaptive-black-queen-loss-rozen) [[5. S. cervisiae: Domestication, Gene Duplication, Deletion Strains & Gene Expression, de Winde 14]](#s.-cervisiae-domestication-gene-duplication-deletion-strains-gene-expression-de-winde) [[6. A. niger: Backcrossing, Complementation, Isolation & (Bulk) Segregant Analysis, Ram 17]](#a.-niger-backcrossing-complementation-isolation-bulk-segregant-analysis-ram) [[7. Sequencing: Sanger ddNTP, Short read Illumina, Long Read PacBio & Nanopore, Vriesendorp] ](#sequencing-sanger-ddntp-short-read-illumina-long-read-pacbio-nanopore-vriesendorp) [[8. Genome Assembly Challenges & "-Seq -Omics": ChIP, ATAC, (sc, bulk, spatial) RNA, Vriesendorp 23]](#genome-assembly-challenges--seq--omics-chip-atac-sc-bulk-spatial-rna-vriesendorp) [[9. Lactobacili: Genomic Taxonomy (DNA-DNA, 16sRNA, A/CNI), Phylogeny & Orthogroups, van Noort 27]](#lactobacili-genomic-taxonomy-dna-dna-16srna-acni-phylogeny-orthogroups-van-noort) [[10. Microbiomes: Amplicons, Shotgun, MAGs & Functional Metagenomics, Barona Gómez 31]](#microbiomes-amplicons-shotgun-mags-functional-metagenomics-barona-g%C3%B3mez) [[11. Lichen Microbiome: Case Symbiont Metagenomics in Lichen, Daniel 34]](#lichen-microbiome-case-symbiont-metagenomics-in-lichen-daniel) [[12. Bacteria: MGEs (Plasmids, ICEs, IS/Transposons) & HGT Kusumawardhani 36]](#bacteria-mges-plasmids-ices-istransposons-hgt-kusumawardhani) [[13. Yeast: Genome Assembly, Annotation & Comparison SNPs/SNVs, GWAS, Seekles 38]](#yeast-genome-assembly-annotation-comparison-snpssnvs-gwas-seekles) [[14. B. oleracea: Analyzing Late vs Early Flowering with BSA & QTLs, Vos (Naturalis) 40]](#b.-oleracea-analyzing-late-vs-early-flowering-with-bsa-qtls-vos-naturalis) [[15. Pygmy Pigs & Triturus: Genome Complexity (Inbreeding & BLS, de Visser (Naturalis) 42]](#pygmy-pigs-triturus-genome-complexity-inbreeding-bls-de-visser-naturalis) [[16. Triturus: Chr1 BLS, Recombination Suppression & Supergenes , France (Naturalis) 43]](#triturus-chr1-bls-recombination-suppression-supergenes-france-naturalis) [[17. Humans: Paleosequencing & aDNA, Altena (LUMC) 46]](#humans-paleosequencing-adna-altena-lumc) [[18. Humans: Genetics, Genomics and Human Health, Voshol (GenomeScan) 48]](#humans-genetics-genomics-and-human-health-voshol-genomescan) [[19. Humans: Non-Invasive Prenatal Testing, Valk (GenomeScan) 50]](#humans-non-invasive-prenatal-testing-valk-genomescan) 1. Basics: Genomic Diversity, Central Dogma, Eukaryotes vs Prokaryotes, de Winde ================================================================================ **Abstract** This presentation delves into genome diversity, exploring the organization and complexity of genetic material across various life forms. It begins by defining genomic architecture, emphasizing the spatial and functional arrangement of elements like genes and regulatory regions. Key genetic processes, such as DNA replication, transcription, and translation, are covered under the central dogma of molecular biology. The presentation contrasts prokaryotic and eukaryotic genomes, highlighting differences in gene number, genome size, and noncoding DNA. Mechanisms like mutations, gene duplications, and horizontal gene transfer are discussed as drivers of genetic variation and evolution. Additionally, it explores the hybrid origin of eukaryotic genomes, tracing the bacterial ancestry of mitochondrial and chloroplast DNA. The role of model organisms in studying genome evolution is also examined, showcasing how genetic diversity fuels species evolution and adaptation. **Key Concepts** 1. - 1. - 2. - - - - - - 3. - - 4. - - - - - - - - 5. - - 6. - - - - - 7. - 8. - 2. Basics: Structure & Function of DNA & RNA, Verschoor ======================================================= **Abstract** This presentation explores the foundational principles of genomics, focusing on DNA as the molecular basis of life. It covers the chemical structure of DNA, the process of replication, and the central dogma of biology, which explains the flow of genetic information from DNA to RNA and proteins. Key differences between prokaryotic and eukaryotic transcription and translation are outlined, along with gene regulation mechanisms and the role of epigenetics in controlling gene expression. The importance of DNA in scientific research, including its application in technologies such as PCR, is highlighted. Through an understanding of these processes, the presentation emphasizes the relevance of genomics in modern biology and its impact on cell function, organism development, and genetic research. **Key Concepts** 1. 2. - - 3. **Prokaryotic vs. Eukaryotic Gene Expression:** 4. - - - - - 5. In **eukaryotes**, transcription takes place in the nucleus and involves more complex regulation: - - - - 6. 7. 8. 9. 3. Phages: Lytic & Lysogenic cycle, Bacterial Defenses & Co-evolution, Mabrouk ============================================================================== **Abstract** This presentation explores the genomic architecture and evolutionary dynamics of bacteriophages, the most abundant biological entities on Earth. Bacteriophages are viruses that infect bacteria, and play a pivotal role in shaping bacterial populations and ecosystems. The presentation highlights the diversity of phage genomes, phage-host interactions, and the mechanisms bacteria use to resist phage infections, such as restriction-modification systems, CRISPR, and biofilm production. Phage therapy\'s resurgence, especially in the context of antibiotic resistance, is also discussed. Additionally, the presentation delves into coevolution between phages and bacteria, the trade-offs in bacterial defense strategies, and novel bacterial escape mechanisms, such as cell wall deficiency, which may allow survival from phage infection. **Key Concepts** 1. 2. 3. - - ### 1. **Adsorption Blocking**: **preventi**ng **p**hage attachment to receptors or pili - - ### 2. **Uptake Blocking**: monopolize **the** host **by preventing** other DNA uptake or injection - - ### 3. **Restriction-Modification (R-M) Systems**: cleavage of unmethylated invasive phage DNA - - ### 4. **CRISPR-Cas Systems**: search & destroy by memorized phage DNA templates (spacers) - - - - - - - ### 5. **Abortive Infection (Abi)**: cell suicide - - - 4. - - - - 5. 6. 4. Bacterial Symbionts: Genomic Size, Drift, HGT & Adaptive "Black Queen" Loss, Rozen ===================================================================================== ### Abstract This presentation explores bacterial genome evolution with a focus on the dynamics of genome size, population size, horizontal gene transfer (HGT), and the concept of pangenomes. It examines the symbiosis between aphids and *Buchnera aphidicola*, highlighting how symbiont genomes experience significant gene loss due to restricted environments and small population sizes. Key evolutionary mechanisms such as genetic drift, natural selection, and Muller's ratchet are discussed to explain genome reduction in bacterial symbionts. The role of HGT in expanding genomes, particularly in species with large effective population sizes (Ne), is also explored, along with the implications for gene transfer across diverse environments. Additionally, the presentation introduces the concept of pangenomes, emphasizing the variability in gene content among bacterial species and how environmental factors influence the retention of transferred genes.  ### Key Concepts 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 5. *S. cervisiae*: Domestication, Gene Duplication, Deletion Strains & Gene Expression, de Winde ================================================================================================ **Abstract** This presentation explores the genomics of *Saccharomyces cerevisiae*, commonly known as baker's yeast. It begins with an introduction to yeast as a eukaryotic model organism, highlighting its genome, evolutionary background, and role in industrial biotechnology. The presentation delves into key concepts such as genome sequencing, gene duplication, and the functional significance of open reading frames (ORFs). Additionally, it discusses yeast's domestication and strain diversity, including deletion strains used in research. Antisense transcription and genome-wide RNA-seq analysis in yeast under stress conditions are presented, showcasing the complexity of gene expression regulation. **Key Concepts** 1. 2. - - - - - 3. 4. 5. 6. 7. 6. *A. niger*: Backcrossing, Complementation, Isolation & (Bulk) Segregant Analysis, Ram ======================================================================================== ### Abstract The presentation focuses on the genomic architecture of *Aspergillus niger*, an industrially important fungus used in enzyme and citric acid production. It details the application of genome sequencing and systems genetics to identify mutations responsible for certain phenotypes, particularly UV-induced mutants. Key methodologies such as **backcrossing**, **multiple mutants in one complementation group, segregation analysis, and bulk segregant analysis (BSA)** are employed to reduce non-relevant mutations and identify critical genetic changes. The study emphasizes classical genetics\' synergy with modern sequencing techniques, providing insights into mutation identification and genome organization. Additionally, the parasexual cycle of *A. niger* is highlighted as a tool for genetic crossing in the absence of a known sexual cycle. ### Key Concepts 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. - - - - - - **Key Terms**: - - - - 7. Sequencing: Sanger ddNTP, Short read Illumina, Long Read PacBio & Nanopore, Vriesendorp ========================================================================================== **Abstract**\ This presentation explores the advancements in DNA sequencing technologies from the first-generation Sanger method to next-generation and third-generation sequencing platforms. It highlights key innovations in sequencing techniques, including Illumina's high-throughput, real time sequencing-by-synthesis (requiring amplification), Pacific Biosciences' real-time single-molecule sequencing, and Oxford Nanopore's nanopore sensing. The evolution of sequencing has increased the scale and efficiency of DNA analysis, enabling extensive applications in genomics, structural studies, and base modification detection. Key aspects like read length, throughput, error rates, and amplification challenges are discussed, demonstrating how each platform serves different scientific needs.  **Key Concepts** **DNA Sequencing Generations**: 1. 2. - - - - - - 3\. **Second Generation (NGS):** The PacBio sequencing method, also known as **Single-Molecule, Real-Time (SMRT) sequencing**, works as follows: - - - - This method allows for **very long reads** and can be used for genome assemblies and structural studies. - 3. - 4. - 5. - 6. - 8. Genome Assembly Challenges & "*-Seq -Omics*": ChIP, ATAC, (sc, bulk, spatial) RNA, Vriesendorp ================================================================================================= ### Abstract This presentation covers the complex processes of genome assembly and functional genomics, emphasizing the challenges posed by sequencing technologies and the insights gained from gene expression analysis. Genome assembly faces technical issues, such as short read lengths and errors, making it difficult to reconstruct full chromosomes. Functional genomics explores how genes contribute to phenotypes through cellular mechanisms such as gene expression and chromatin structure. Key experimental techniques like ChIP-seq, ATAC-seq and RNA-seq are highlighted, which provide deep insights into gene expression, epigenetic regulation, and cellular diversity. The presentation also touches on cutting-edge technologies like single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics, which are revolutionizing developmental biology by uncovering heterogeneity at the single-cell level. ### Key Concepts The presentation outlines three major problems in genome assembly: 1. **Sequencing Limitations**: 2. **Technical Errors**: 3. **Genomic Architecture and Assembly**: 4. - - - - 5. - - - - 6. - - - - - 9. *Lactobacili*: Genomic Taxonomy (DNA-DNA, 16sRNA, A/CNI), Phylogeny & Orthogroups, van Noort =============================================================================================== ### Abstract This presentation delves into the genomic architecture and taxonomy of species, particularly focusing on Lactobacillus, a bacterial genus of significance in both human health and industry. Traditional methods of bacterial taxonomy, including DNA-DNA hybridization and 16S rRNA, are compared with newer genomic techniques such as Average Nucleotide Identity (ANI) and Core Nucleotide Identity (CNI). These methods enhance the accuracy of species classification by analyzing single-copy orthologous genes across genomes. The presentation explores key processes in molecular evolution, including gene duplication, divergence, and the orthology-paralogy relationship, while highlighting advancements in species taxonomy facilitated by genomics. Specific examples of genome-based taxonomy adjustments in Lactobacilli are provided, emphasizing the resolution of inconsistencies and identification of new species. ### Key Concepts 1. 2. - - - - 3. 4. 5. - - 6. 7. 8. 9. 10. - - - - - - - - 11. 12. - - - - 10. Microbiomes: Amplicons, Shotgun, MAGs & Functional Metagenomics, Barona Gómez ================================================================================= ### *The lecture recording was from 2023 with a slightly different presentation than in 2024* ### Abstract This presentation explores the role of metagenomics in microbiome research and its impact on modern microbiology. It covers the evolution of community genomics through amplicon-based and shotgun metagenomics techniques, expanding the tree of life, and elucidating microbial interactions via co-occurrence networks. The discussion highlights the use of metagenome-assembled genomes (MAGs) and single amplified genomes (SAGs) in resolving microbial community structure and function. Functional metagenomics is presented as a powerful approach for studying enzyme activity and natural product biosynthesis, with a case study on microbial lichen symbionts. The presentation underscores the significance of metagenomics in bridging microbial ecology and genomics across scales. ### Key Concepts 1. 2. - - - 3. - - 4. 5. - - - - - - 6. 7. 8. - - - - 9. 11. Lichen Microbiome: Case Symbiont Metagenomics in Lichen, Daniel =================================================================== ### Abstract Lichens are symbiotic organisms primarily composed of a fungal partner (lichen-forming fungi) and a photobiont (algal or cyanobacterial), with a diverse array of bacterial associates. Recent advances in metagenomics have revealed more complexity in these associations than previously thought, showing additional fungal species and varied bacterial communities within lichens. To explore these relationships, metagenomic sequencing across hundreds of lichen species was performed. Analyses included genome assembly, binning, and occurrence studies to identify core symbionts, bacterial functions, and their ecological roles. Using tools like CONCOCT and MetaBAT2, genomes were reconstructed, revealing high diversity and strain-level variations. The study highlights how sequencing depth impacts genome recovery, with some metagenomes yielding no high-quality fungal or photobiont genomes. The work underscores the importance of microbial diversity in lichen symbiosis and how bacteria may play essential, yet understudied, roles in lichen ecology and metabolism. ### Key Concepts: 1. - 2. - - 3. - 4. - 5. - - - 6. - - 12. Bacteria: MGEs (Plasmids, ICEs, IS/Transposons) & HGT Kusumawardhani ======================================================================== **Abstract** Mobile genetic elements (MGEs) play a crucial role in horizontal gene transfer (HGT) in bacteria, which significantly contributes to genetic diversity and evolution. These elements include conjugative plasmids, transposons, integrative and conjugative elements (ICEs), and bacteriophages. HGT processes such as transformation, conjugation, and transduction allow bacteria to acquire new genetic material, including virulence factors and antibiotic resistance genes. MGEs facilitate the mobility of these genes, impacting bacterial adaptability and genome plasticity. Understanding MGEs is essential for studying bacterial evolution, antimicrobial resistance, and their applications in genetic engineering and synthetic biology. Various methods, including metagenomic analysis and reporter constructs, are used to study MGEs, which are also leveraged as tools in bioengineering and biotechnology. **Key Concepts** 1. - - - **Mobile Genetic Elements (MGEs):** MGEs are vehicles of genetic material and include: 2. - - - 3. 4. 5. 6. 7. 13. Yeast: Genome Assembly, Annotation & Comparison SNPs/SNVs, GWAS, Seekles ============================================================================ ### Abstract This presentation provides a comprehensive overview of genome comparison techniques, focusing on the workflow from raw sequence reads to annotated genomes, and further into the analysis of genome variants. It introduces essential tools such as FastQC for quality control, SPAdes for genome assembly, and Augustus/Braker2 for genome annotation. Special attention is given to comparing genomes, with discussions on single nucleotide polymorphisms (SNPs), single nucleotide variants (SNVs), and larger genomic changes. Case studies, including a UV-mutant yeast strain and Penicillium roqueforti, illustrate practical applications. Techniques such as Bowtie2 for reference mapping and SnpEff for predicting the impact of mutations are also explained. The final steps include visualizing genomic data using IGV and interpreting SNVs with tools like PLINK, with methods of experimental validation highlighted. The presentation emphasizes the need for both computational and experimental approaches to confirm findings. ### Key Concepts 1. 2. - - - 3. 4. 5. 6. 7. 8. 9. 10. 14. *B. oleracea*: Analyzing Late vs Early Flowering with BSA & QTLs, Vos (Naturalis) ===================================================================================== **Abstract** The presentation explores the genomics behind quantitative traits, focusing on *Brassica oleracea*. Using flowering time as an example, it explains how quantitative traits---measurable phenotypes influenced by multiple genes and the environment---vary across populations. The research leverages Bulk Segregant Analysis (BSA) to study flowering time regulation in the Jersey Kale through crosses with the TO1000DH3 line. DNA sequencing of phenotypic bulks reveals quantitative trait loci (QTLs) linked to flowering time. The findings identify several significant QTLs, some involving paralogs. Enrichment analyses of gene ontology (GO) terms help refine these results, highlighting pathways contributing to the flowering process. Notably, genes like TSF, previously unlinked to flowering in *B. oleracea*, emerge as contributors. The study concludes that phenotyping and sequencing trait extremes can reveal underlying single nucleotide polymorphisms (SNPs), but refinements are necessary to filter relevant gene functions. **Key Concepts:** 1. 2. 3. 4. 5. 6. 7. 15. Pygmy Pigs & *Triturus:* Genome Complexity (Inbreeding & BLS, de Visser (Naturalis) ======================================================================================= ### Abstract This presentation explores the genomic architecture of complex eukaryotes, with a focus on two organisms: the critically endangered pygmy hog (*Porcula salvania*) and *Triturus* newts. The first part delves into the implications of inbreeding in the pygmy hog, including the loss of genetic diversity and the presence of regions of homozygosity (ROH), which highlights the challenges for conservation. The second part introduces the enigmatic genome of *Triturus* newts, emphasizing the \"balanced lethal system\" (BLS) and its reproductive consequences. This system reduces the survival rate of offspring due to lethal alleles on certain chromosomes. The lecture highlights how genomic architecture, rather than natural selection, may contribute to these unusual genetic phenomena. ### Key Concepts 1. - - 2. 3. - - 4. - 5. - 16. Triturus: Chr1 BLS, Recombination Suppression & Supergenes , France (Naturalis) =================================================================================== ### Abstract This presentation explores the concept of a balanced lethal system within the context of evolutionary biology, focusing on the Triturus species. A balanced lethal system arises when two alleles are required for survival, creating a genetic scenario where recombination could potentially disrupt the balance. The discussion emphasizes how recombination is suppressed on specific chromosomes, particularly chromosome 1, leading to the accumulation of deleterious mutations through mechanisms like Müller's ratchet. Furthermore, the presentation investigates the implications of supergenes---large non-recombining regions that behave as single genes---within this framework, and poses the question of whether such genetic structures could be remnants of historical sex chromosomes. ### Key Concepts 1. - - 2. - - - - - 3. - - 4. - - 5. 6. ### 1. **How Linkage Mapping Works**: - - - ### 2. **Importance of Linkage Mapping in the Context of *Triturus***: - - - - - ### 3. **Broader Implications**: - 7. - - 17. Humans: Paleosequencing & aDNA, Altena (LUMC) ================================================= ### *The lecture presentation was different from the Brightspace presentation* ### Abstract The presentation explores the field of ancient DNA (aDNA) research, focusing on its applications in understanding human evolution, ancestry, and disease. It discusses challenges like DNA degradation and contamination, as well as sampling techniques to mitigate these issues. The development of sequencing technologies such as shotgun sequencing and hybridization DNA capture is highlighted. The presentation covers the impact of aDNA on areas such as paleo-epidemiology, kinship, and social structures. Several case studies illustrate how ancient DNA contributes to our knowledge of human migration, genetic drift, and the co-evolution of humans with pathogens. The future of aDNA research promises further advancements in understanding human history and health. ### Key Concepts 1. - 2. - 3. - - - - 4. - - - 5. - - - 6. - 7. - 18. Humans: Genetics, Genomics and Human Health, Voshol (GenomeScan) ==================================================================== ### Abstract The presentation on \"Genomics and Human Health\" outlines the relationship between genetics, genomics, and health. Genetics focuses on the study of individual genes and their inheritance patterns, while genomics examines the entire genome and its interactions with environmental factors. A significant portion of global health issues, such as genetic disorders, stems from mutations in genes or chromosomes. Advances in genomics have facilitated key applications, including personalized cancer treatments, prenatal testing, and diagnostics for rare diseases. Genomic medicine is evolving to integrate multi-omics data, allowing a deeper understanding of disease mechanisms. Technological advances like Next-Generation Sequencing (NGS) and bioinformatics platforms like DRAGEN enhance the speed and accuracy of genetic testing. Understanding the patterns of inheritance---autosomal, X-linked, mitochondrial---is crucial for diagnosing monogenic, polygenic, and chromosomal disorders. The future of genomics lies in preventive medicine, pharmacogenomics, and improved ethnic diversity in genomic databases. ### Key Concepts 1. 2. 3. - - - - - 4. 5. - - - - 6. - - - - - - 7. 8. - - - - 19. Humans: Non-Invasive Prenatal Testing, Valk (GenomeScan) ============================================================ **Abstract** Non-Invasive Prenatal Testing (NIPT) has become a widely used method for detecting chromosomal abnormalities, such as trisomy 13 (Patau syndrome), trisomy 18 (Edwards syndrome), and trisomy 21 (Down syndrome), early in pregnancy. NIPT analyzes cell-free fetal DNA present in maternal blood to assess potential genetic anomalies, offering a non-invasive alternative to previous invasive techniques. With a high detection rate and low false positive rate, NIPT is more reliable than the older combined test, which involved ultrasound and blood analysis. This presentation covers the principles of NIPT, its practical application, data analysis methods, and the bioinformatics processes that ensure its accuracy. It also discusses methods to estimate fetal DNA fractions and how the technology has been implemented in clinical practice, particularly in Rotterdam. **Key Concepts** 1. - - 2. - - 3. - - 4. - - 5. - - -