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BIOL4210 Lecture 1: Cell & Molecular Biology – Key Concepts

The Universal Features of Cells on Earth

  • BIOL4210 – Lecture 1: overview of cell & molecular biology and why cell biology is foundational in biology.
  • Videos are topic-broken, bite-sized (usually 10–20 minutes) to reinforce key topics and cover material not fully addressed in longer class sessions.
  • Central claim: cell biology is vitally important and arguably the most important subdiscipline in biology; early topics preview the course focus: structure of the cell, DNA, the central dogma, and enzymes.
  • Life on Earth spans a wide range of environments, including extremophiles and anhydrobiotic organisms that survive with minimal water.
    • Examples of extreme environments: desert plants (e.g., cacti), Pompeii worms at hydrothermal vents.
  • All life can be grouped into three domains based on evolutionary relationships: Bacteria (Eubacteria), Archaea, and Eukaryotes. These domains can be drawn as a tree derived from ribosomal RNA (rRNA) sequence comparisons.
    • Greater number of differences in rRNA sequences implies greater evolutionary distance.

The Three Domains of Life and the Tree of Life

  • Bacteria (Eubacteria): simple, single-celled organisms with no nucleus or membrane-bound organelles.
    • Examples: E. coli (gut bacterium) and cyanobacteria (photosynthesis-capable).
  • Archaea (Archaebacteria): superficially resemble bacteria but process information like eukaryotes; often extremophiles with diverse energy sources.
    • Notable species mentioned:
    • Haloferax volcanii: halophilic mesophile; hypersaline environments (e.g., Dead Sea); moderate temperatures.
    • Sulfobus: acidophile and thermophile; optimally oxidizes sulfur using sulfur as a final electron acceptor; thrives at pH 2–3.
    • Methanococcus: methane production; mesothermophilic or hyperthermophilic.
    • Note: the first eukaryotes are thought to have evolved when an anaerobic archaeon internalized an aerobic bacterium ~1.6 billion years ago.
  • Eukaryotes: membrane-bound organelles; genetic material in a nucleus; mitochondria; chloroplasts in some
    • Examples include unicellular flagellate protozoa (e.g., Trypanosoma), Paramecium, and Dictyostelium (slime mold) which bridges single-celled eukaryotes and multicellular organisms.
  • Emphasis (not a taxonomy course): the diagram illustrates diversity and the core point that all life is cellular (Cell Theory).

Cell Theory and Shared Cellular Features

  • Core assertion: all life is cellular; life begins as a single cell and all mature forms arise from cellular processes.
  • All cells share foundational features and biochemical processes, with some organismal differences.
  • Common cellular features highlighted in the lecture:
    • Plasma membrane bounds the cell and regulates entry/exit of nutrients and wastes; membrane contains receptors for stimuli and mediates interactions with other cells and the extracellular matrix.
    • DNA as hereditary information stored in a universal chemical language; nearly all cells use the same genetic code.
    • Transcription: copying DNA to RNA to make temporary RNA transcripts.
    • Translation: reading RNA to synthesize proteins; molecular machinery for transcription and translation is often similar across diverse species (prokaryotes and eukaryotes).

DNA, RNA, and the Central Dogma

  • DNA structure basics:
    • Nucleotides: A, G, C, T; sugar-phosphate backbone forms the DNA strand.
    • Base-pairing rules: A\;\text{pairs with}\;T\quad\text{and}\quad G\;\text{pairs with}\;C
    • Double helix: two strands with sugar-phosphate backbones on the outside and bases paired in the center; strands can be separated for reading (transcription) or replication.
  • Central dogma recap:
    • DNA is transcribed to RNA, which is translated to proteins.
    • All cells use transcription and translation to produce proteins; the basic language (codons) is conserved across many organisms.
  • RNA as an intermediate:
    • RNA is a temporary information carrier; DNA is a stable archive.
    • DNA is copied and maintained with repair mechanisms; RNA copies can be turned on/off as needed.
  • Discussing genome-wide equivalence:
    • The same genetic code is read by a similar translational machinery across diverse life forms; recombinant proteins can be produced by expressing human cDNA in bacteria.
    • However, there are grammatical differences (e.g., introns in eukaryotes; prokaryotes generally lack introns).
  • Intron vs exon concept:
    • Eukaryotes contain introns and exons; prokaryotes generally lack introns.

The Genetic Code, Transcription, and Translation Mastery

  • The genetic code is largely universal across life; codons map to amino acids in a conserved manner.
  • The same codons can specify amino acids in different species, enabling cross-species gene function (e.g., human genes rescuing yeast, fly, or mouse mutants).
  • RNA intermediates are used to translate DNA into proteins via the transcription-translation pipeline.
  • Distinctions between transcription and translation: transcription copies DNA into RNA; translation uses RNA as a template to synthesize proteins.

Enzymes and Biological Catalysis

  • Enzymes are proteins that catalyze chemical reactions, enabling metabolism, replication, and growth.
  • Enzymes can drive anabolic (building) or catabolic (breaking) reactions; they speed up reactions by lowering activation energy.
  • Lysozyme: classic enzyme example; structure solved by X-ray crystallography (1960s); natural antibiotic found in egg white, saliva, tears, and secretions.
    • Mechanism: 3D fold creates an active site; substrates must fit the site and form weak non-covalent interactions with active-site residues.
    • Substrate example: polysaccharide chains in bacterial cell walls; lysozyme hydrolyzes these chains, causing bacterial cell lysis due to internal pressure.
  • Why enzymes matter: catalysis is fundamental to life; life can be viewed as autocatalytic (self-replicating) because polynucleotides (DNA/RNA) encode proteins (including enzymes) that drive synthesis of more nucleotides and more proteins, enabling growth and replication.

Genes, Genomes, and Regulation

  • What is a gene? Various definitions; for this course:
    • A gene is a region of DNA that codes for a distinct RNA molecule, which may be translated to produce a protein; some genes code for RNAs that are not translated (e.g., rRNA, tRNA).
  • The genome is the entire genetic information content of an organism (all DNA).
    • For humans: 3.2\times 10^{9}\text{ base pairs}, containing roughly 3.0\times 10^{4}\text{ genes}.
  • Gene expression and regulation:
    • Not all genes are on all the time; gene expression can be upregulated or downregulated in response to stimuli.
    • In multicellular organisms, a single genome can give rise to many cell types (cell phenotypes) due to differential gene expression.
    • Genes have coding regions (exons) and regulatory regions that control transcription; regulatory elements can respond to transcription factors and co-regulators.
    • Genes can form simple or complex circuits; some genes regulate other genes, enabling feedback and regulatory networks (topic to be explored in future sessions).
  • Minimal genome concept:
    • A minimal set of around 3\times 10^{2} genes appears sufficient for a viable cell.
    • A core of about 60 genes is shared by all living species (universal core).
    • Most species have more genes than this minimal set; typical bacterial/archaeal genomes contain roughly between 10^{3} and 6\times 10^{3} genes, with eukaryotes having many more.
  • Gene duplication and the birth of gene families:
    • Gene duplication creates copies of existing genes; duplicates can evolve new or similar functions.
    • Gene families are sets of genes related by sequence and derived from a common ancestral gene.
    • A large cross-species study (50 bacteria, 13 archaea, 3 eukaryotes) identified about 4873 protein-coding gene families; among these, about 264 are ancient and conserved across life, with only about 60 truly ubiquitous across all life forms.
    • Of the ubiquitous families, many are tied to fundamental cellular processes (e.g., translation) with explicit counts such as 63 translation-related families and 43 related to amino acid transport/metabolism in the cited breakdown.

Genomes, Genome Size, and Gene Content

  • Genome size is the total number of base pairs in a haploid genome (one copy).
    • Ploidy (e.g., diploid in many sexually reproducing organisms) means somatic cells contain multiple copies of the genome.
    • Genome size is not simply the number of genes; it includes intergenic regions, regulatory DNA, and repetitive elements.
  • Prokaryotes tend to have small genomes; eukaryotes tend to have larger genomes, influenced by noncoding regions and transposable elements.
  • Examples and trends:
    • Escherichia coli: genome size ≈ 4.6\times 10^{6}\text{ bp}; about 4\,300\text{ genes}; roughly 11\% noncoding DNA.
    • Human genome: size ≈ 3.2\times 10^{9}\text{ bp} with about 3.0\times 10^{4}\text{ genes}; only about 2.0\times 10^{4} are protein-coding; approximately 98.5\% of the genome is noncoding.
    • Zebrafish: genome size is under half that of humans but contains more genes than humans (demonstrating that gene count is not strictly proportional to genome size).
    • Caenorhabditis elegans: genome ≈ 1.3\times 10^{8}\text{ bp} with about 21{,}000\text{ genes} (roughly two-thirds the human gene count).
  • Trends: genome size and gene content vary widely even among closely related organisms; larger genomes in eukaryotes are often due to expanded noncoding regions (regulatory DNA) and parasitic transposable elements.

Minimal Genome, Gene Families, and Genome Diversity

  • The idea of a minimal viable genome links to a core set of essential genes; additional genes expand capabilities, niche adaptation, and regulatory complexity.
  • Gene duplications create families that diversify function over evolutionary time; some gene families are ancient and conserved; others are lineage-specific.
  • Understanding genome size vs gene content helps explain why some organisms with fewer genes have large genomes due to noncoding DNA and repetitive elements.

Model Organisms in Biology

  • What is a model organism? Species frequently used to study basic biology and to address specific questions in a controlled, ethical manner.
    • Range from simple prokaryotes to multicellular vertebrates (e.g., mice).
    • Key reasons to use model organisms:
    • Genomes are often fully sequenced and gene functions can be studied in a tractable context.
    • They are genetically manipulable (e.g., tools like CRISPR/Cas9).
    • They are easy to propagate and breed in lab settings.
    • Rationale for cross-species studies: highly conserved genes and pathways allow inference about human biology by studying orthologues in simpler organisms; some contexts (e.g., aging) are more practical in short-lived models like mice.
    • Ethical considerations: many questions cannot be ethically tested in humans; model systems provide ethical means to study fundamental biology and disease models.
  • Cell lines vs whole organisms:
    • Cell lines (primary cells or immortalized) are powerful for studying cellular processes in isolation but may not recapitulate in vivo tissue architecture and interactions.
    • Whole-organism models capture complex interactions, development, and systemic effects.
    • Cancer research often uses both approaches: cell lines for mechanistic studies and mouse models for tumor progression and therapy testing.

Classic Model Organisms: Strengths and Weaknesses

  • E. coli (bacteria):
    • Strengths: grows rapidly; easy to manipulate genetically; glycerol stocks allow easy storage; excellent for basic cellular processes and cloning.
    • Weaknesses: prokaryotic cell structure is quite different from human cells; limited direct relevance to human health/disease without additional context.
  • Saccharomyces cerevisiae (baker’s yeast):
    • Strengths: simple eukaryote with mitochondria; can reproduce vegetatively or sexually; small genome; sequence available since 1997; ~6,600 unique proteins; many human proteins have functional equivalents.
    • Contributions: valuable for studying cell cycle regulation, mitosis, and basic eukaryotic processes.
  • Arabidopsis thaliana (model plant):
    • Strengths: small, fast-growing; easily cultivated indoors; thousands of offspring in ~8–10 weeks; extensive genetic resources.
    • Key use: circadian clock and plant biology.
  • Caenorhabditis elegans (nematode):
    • Strengths: microscopic, transparent; defined somatic cell lineage (~959 cells); well-mapped development; useful for aging, reproduction, stress response, nervous system development; transparent fluorophore-based live imaging.
  • Drosophila melanogaster (fruit fly):
    • Strengths: long history in genetics (>80 years); polytene chromosomes enable genetic mapping; many mutant phenotypes named (e.g., hedgehog, swiss cheese, Wingless, tinman);
    • Weaknesses: sometimes simpler anatomy compared with vertebrates; not all genes have direct vertebrate equivalents.
    • Practical details: rapid generation time (~9 days from egg to adult).
  • Zebrafish (Danio rerio):
    • Strengths: transparent embryos for the first ~2 weeks; useful for developmental biology and embryology studies; compact genome (~half human/mouse genome size) and rapid generation (~3 months);
    • Genetic engineering is relatively straightforward with modern tools.
  • Xenopus species (frogs):
    • Xenopus tropicalis: small, diploid genome; easy genetic handling.
    • Xenopus laevis: larger genome, not strictly diploid due to genome duplication; good for embryology studies because embryos are large and develop outside the mother.
  • Mice (Mus musculus):
    • Strengths: predominant mammalian model; inbred strains provide genetic uniformity; high relevance to human biology and disease; well-developed genetic tools.
    • Caveats: differences between mice and humans require cautious translation; still widely used due to physiological similarity and practical advantages.

Choosing Model Systems: Practical Considerations

  • Researchers choose models to match questions:
    • Simple systems to dissect basic processes (e.g., E. coli, yeast).
    • Organismal context for development and physiology (e.g., zebrafish, Xenopus, mice).
  • Tools and capabilities that influence choice:
    • Fully sequenced genomes and genetic tractability (e.g., CRISPR/Cas9).
    • Ability to propagate and generate sufficient sample sizes in lab conditions.
  • Ethical considerations drive the use of non-human models and cell lines for many experiments.
  • Limitations of models:
    • In vitro cell lines cannot fully recapitulate in vivo tissue organization and interactions.
    • Differences between model organisms and humans mean findings require careful translation.

Connections to Foundational Principles and Real-World Relevance

  • The material ties back to foundational principles from earlier lectures: cell theory, universal genetic code, and the central dogma as the backbone of molecular biology.
  • Real-world relevance includes:
    • Understanding basic cellular processes informs medicine, biotechnology, and understanding disease mechanisms.
    • Model organisms enable genetic dissection of pathways relevant to aging, development, cancer, and metabolism.
    • Genome size and gene content concepts help explain evolutionary strategies across life and inform synthetic biology and minimal-genome research.

Notable Numerical Highlights and Quick Facts

  • Genome size and gene counts:
    • Human genome: 3.2\times 10^{9}\text{ base pairs}; ≈ 3.0\times 10^{4}\text{ genes}; ≈ 2.0\times 10^{4}\text{ protein-coding genes}; ≈ 98.5\% noncoding DNA.
    • Escherichia coli: 4.6\times 10^{6}\text{ bp}; ≈ 4\,300\text{ genes}; ≈ 11\% noncoding DNA.
    • C. elegans: 1.3\times 10^{8}\text{ bp}; ≈ 21{,}000\text{ genes}.
    • Mycobacterium genitalium: ~530\text{ genes} total; ~400\text{ essential}; ~43\text{ RNA genes}; ~339\text{ protein-coding}.
  • Core universal gene set:
    • A minimal core around 60 genes is shared by all living species.
    • A minimal viable genome is estimated to require about 3\times 10^{2} genes; a substantial number of species have far more genes due to duplication and expansion.
  • Genome size vs gene count examples illustrate that larger genome size does not always correlate with more protein-coding genes; noncoding DNA contributes substantially to genome size in eukaryotes.
  • Key historical notes:
    • Endosymbiotic theory: eukaryotic organelles (mitochondria, chloroplasts) originated from bacteria via endosymbiosis, with eukaryotes acquiring mitochondria from an aerobic bacterium about 1.6\text{ billion years ago}.
    • The genetic code’s universality is evidenced by cross-species expression (e.g., human genes rescuing non-human homologs).

Quick Reference: Key Terms

  • Cell Theory: all life is cellular; cells are the basic unit of life; all life arises from cell division.
  • Central Dogma: DNA -> RNA -> Protein via transcription and translation.
  • Genome: total genetic content of an organism.
  • Gene: DNA region encoding an RNA molecule (which may be translated to a protein).
  • Introns vs Exons: introns are noncoding sequences within genes in many eukaryotes; exons encode the final RNA sequence.
  • Gene Family: set of genes related by sequence due to duplication from a common ancestor.
  • Model Organism: species used to study biological processes to infer principles applicable to other organisms, including humans.
  • Autocatalysis: a self-reinforcing process where products (e.g., enzymes, nucleotides) promote their own synthesis and replication.
  • Endosymbiosis: evolutionary process in which one cell lives inside another and eventually becomes a functional organelle (mitochondria, chloroplasts).
  • Regulatory Regions: parts of a gene that interact with transcription factors to control gene expression.
  • Ploidy: number of genome copies per cell (e.g., diploid in many animals).
  • Noncoding DNA: portions of the genome not encoding proteins (regulatory elements, repeats, transposons).