Comparative Genomics and Endosymbiotic Theory

Comparative Genomics

• Shared Genes: Bacteria and Eukarya share 20% of genes, primarily for metabolic functions (like glycolysis). Archaea and Eukarya share 10% of genes, mostly for information processing (DNA replication).
• Unique Genes: 70% of eukaryotic genes are unique to Eukarya.
• Core Genome: All strains of a species share these genes.
• Flexible Genome: Genes not shared by all strains.
• Pan-Genome: All genes present in strains of a species.
• Applications: This approach can analyze both closely related and highly divergent organisms.

Endosymbiotic Theory

• Origin of Eukaryotic Cells: Eukaryotic cells arose from one prokaryotic cell engulfing another.
• Mitochondria: Derived from aerobic respiration-capable cells.
• Chloroplasts: Derived from oxygenic photosynthesis-capable cells.
• Evidence: Both mitochondria and chloroplasts possess outer and inner membranes, bacterial-like ribosomes, and circular chromosomes.

Serial Endosymbiosis

• Sequential Engulfment: Archaeal cells sequentially engulfed other cells to form mitochondria and chloroplasts.

Symbiogenesis

• Symbiosis First: Archaeal cells formed a symbiotic relationship with the ancestor of mitochondria before developing a nucleus.

LUCA (Last Universal Common Ancestor)

• The hypothesized ancestor of all living organisms.

Microbial Systematics

• Phylogeny: Evolutionary history of organisms, inferred from genetic relatedness.
• Phylogenetic Tree: Diagram displaying evolutionary relationships; branch length signifies relatedness.
• Classification: Grouping organisms into taxa.
• Nomenclature: Naming groups of organisms systematically.
• Molecular Clocks: Using molecules to track the timing of lineages branching apart. It requires similar function in the different organisms in order to work properly.

Species Definitions (Prokaryotes & Higher Organisms)

• Higher Organisms: A species is a group of interbreeding organisms reproductively isolated from other groups.
• Prokaryotes: A species is a collection of strains with shared stable phenotypic and genotypic traits, descended from a common ancestor.

Strain Criteria (Prokaryotes)

• 16S rRNA sequence similarity: 97%+ similarity indicates same species.
• DNA hybridization: >70% genomic sequence hybridization suggests same species.
• Average nucleotide identity (ANI): >95% similarity in orthologous genes implies same species.

Bacterial Names

• Consist of genus + species + strain

Taxon

• A set of microbes that share a predefined level of similarity.

Candidatus

• A new species described from genetic data but with no cultured strains. Must be documented and strains kept in culture collections, and the designated strain is the type strain of the species.

Microbial Ecology

• Population: Assemblage of similar organisms in a specific location.
• Community: Assemblage of populations in a specific location.
• Symbiosis: Prolonged, intimate association of different species.
• Commensalism: One organism benefits, the other is unaffected.
• Mutualism: Both species benefit.
• Parasitism: One species benefits at the expense of another.
• Obligate mutualists: Depend on each other for survival. (Ex. Rhizobium and legumes)

Rhizobia

• Bacteria that form nitrogen-fixing symbioses with plants.

Ectomycorrhizal

• Fungi that colonize within roots of principally forest trees.

Microbe-Insect Relationships

• Many insects have obligate mutualistic relationships with bacteria (vertical transmission). Some can also have relationships that are obligate based on whether it is the microbe being beneficial or not to the host (horizontal transmission).
• Primary symbionts: Mutualism is obligate for both.
• Secondary symbionts: Mutualism is obligate only for the microbe.

Human Microbiome

• All microbes in and on the human body.
• Primarily housed in areas outside the epidermal layers in a healthy host (not organs, etc)

Human GI Tract Microbiome

• Digestion and Nutrients: Site for food digestion and nutrient absorption.
• Mucous Membranes: Lined with mucous membranes.
• Mucin: Glycoprotein layer that inhibits microbial attachment.
• pH Variation: Stomach (very acidic), small intestine (transitional, increases to ~7), large intestine (relatively less acidic).
• Pathogen Colonization: Antibiotics can disrupt the balance, allowing pathogens to emerge. Fecal transplants can help restore normal microflora.
• Clostridium difficile: A gut pathogen typically kept in check by normal gut microbiome

Human Oral Cavity Microbiome

• Mucous Membranes: Lined with a mucous membrane.
• Defense Mechanisms: Saliva with antibacterial enzymes, mechanical flushing, and epithelial cell turnover.
• Dental Plaque: Multispecies biofilm on teeth. Fluoride strengthens calcium phosphate to prevent decalcification.

Human Skin Microbiome

• Acidic Environment: Acidic pH (4-6) due to fatty acids in sweat. Higher microbial density in moister regions.
• Sebum: Sebum further contributes to the acidity of the skin surface from secreted oil.

Pathogen, Infection, and Disease

• Pathogen: Microorganism causing disease.
• Infection: Pathogen growth in or on a host.
• Disease: Host tissue damage due to a pathogen.
• Infection Process: Adherence, invasion, spread.
• Virulence Factors: Traits contributing to pathogenicity.
• Exotoxins: Secreted proteins. Highly toxic and lethal.
• Endotoxins: Outer membrane lipids from Gram-negative bacteria; released upon lysis. Moderately toxic.

Immunology

• Innate Immunity: Broad-spectrum, rapid (hours). Phagocytes are major player.
• Adaptive Immunity: Specific, slow (days). Lymphocytes are major players.

Competitive Exclusion

• Microbiome's ability to outcompete invaders.

Physical and Chemical Barriers

• Physical Barriers: Skin tight junctions, mucociliary escalator, blood-brain barrier
• Chemical Barriers: Stomach acidity, skin secretions, defensins
• Physical and chemical barriers are essential for inhibiting infections.

Lymphatic System

• Lymph: Fluid-like blood, without red blood cells.
• Primary Organs: Thymus and bone marrow— sites where cells responsible for antibody production.
• Secondary Organs: Spleen, lymph nodes, MALT— filter and monitor for pathogens.
• MALT (Mucosa-Associated Lymphoid Tissue): Specialized for pathogens traversing mucous membranes, like M cells of the GI tract.
• Lymph Nodes: Filter lymph, promote interactions between immune cells and pathogens.

Immune System Cells

• Erythrocytes: Red blood cells— oxygen transport.
• Leukocytes: White blood cells— immune response.
• Plasma: Fluid component of blood, without clotting proteins.
• Serum: Plasma minus clotting proteins.
• Monocytes: Circulate in blood, differentiate into macrophages (phagocytes) and dendritic cells (antigen-presenting cells).
• Phagocytes: Ingest and destroy pathogens (Ex. neutrophils, macrophages, dendritic cells)
• Neutrophils: Major circulating phagocytes.
• Eosinophils: Minor phagocytes.
• Basophils and mast cells: Involved in inflammatory response, not phagocytic.

Phagocytosis

• Pathogen uptake and destruction.
• Inflammation, fever, cell death (by NK cells), interferon production are part of the process.
• Pathogens can avoid phagocytosis via various mechanisms like carotenoid production, capsules that are impenetrable, and leukocidins.

Pathogen Recognition

• PAMPs (Pathogen-Associated Molecular Patterns): Surface molecules on pathogens.
• PRRs (Pattern Recognition Receptors): On phagocytes, recognize PAMPs.

MHC-1 & Cellular Immunity Mechanisms

• MHC-1 (Major Histocompatibility Complex 1): Surface proteins on all nucleated cells.
• Virus-infected cells: Often repress MHC-1 genes.
• Cancer cells: Often do not express MHC-1.
• Natural Killer (NK) cells: Recognize and destroy cells lacking MHC-1 (virus-infected or cancer).
• Cytotoxic T cells or T-killer cells use perforin to lyse a cell and granzymes to destroy its contents.

Interferons

• Cytokines: Small soluble proteins affecting cell behavior.
• Viral Inhibition: Stimulate uninfected cells to produce antiviral proteins.

Adaptive Immunity

• Humoral: Antibody-mediated immunity (B cells).
• Cell-mediated: T cell-mediated immunity (T cells).

Antibodies

• B cell receptors (BCRs): Membrane-bound antibodies on B cells.
• T cell receptors (TCRs): Cell surface proteins on T cells bind to antigens.
• Serum: Blood plasma minus clotting proteins.
• Antiserum: Serum with specific antibodies.
• Cross-reactions: Antibodies binding to similar antigens.

Active vs. Passive Immunity

• Active: Long-lived immunity.
• Passive: Short-lived immunity (e.g., from mother to child).

Antibody Functions

• Neutralize toxins
• Block virus binding
• Mark pathogens for destruction by phagocytes or complement
• Complement: Proteins marking pathogens for destruction.

Antigens

• Substances triggering an immune response.
• Epitopes: Specific regions of an antigen recognized by immune system.

B Cell Activation

• B cell activation and antibody production to specific antigens depends on whether the antigen is T dependent or independent

T-Dependent vs. T-Independent Antigens

• T-dependent: Require T cell activation. Not easily recognized by a B-cell.
• T-independent: Activate B cells directly, often multivalent Antigens.

This quiz explores the concepts of comparative genomics, focusing on gene sharing among bacteria, archaea, and eukarya, as well as the endosymbiotic theory which explains the origin of eukaryotic cells. Understand the core and flexible genomes, pan-genomes, and the evidence supporting the evolution of mitochondria and chloroplasts. Test your knowledge on these foundational biological principles.