Cell Biology: Genome Evolution, Cell Signaling, Intracellular Transport, and the Cytoskeleton

Comprehensive practice flashcards covering genome evolution, eukaryotic cell signaling cascades, intracellular compartments and vesicle transport, and cytoskeletal filament dynamics.

According to evolutionary biology, what general principle describes how evolution produces novel genes and genomes?

Evolution acts more as a tinkerer than an inventor, rearranging existing sequences and building on pre-existing themes rather than creating entirely new genes or genomes from scratch.

What are the six basic types of genetic change that drive genome evolution?

1. Mutation within a gene

2. Mutation within regulatory DNA

3. Gene duplication

4. Exon shuffling

5. Mobile genetic elements (transposons)

6. Horizontal gene transfer

Why can only mutations occurring in germ-line cells be passed on to sexually reproducing progeny?

Germ-line cells produce gametes (eggs and sperm) that form the next generation zygote, whereas somatic cells form the body of the individual organism and their mutations are not inherited (though they can cause diseases like cancer).

What are the estimated baseline point mutation rates in Escherichia coli versus humans?

$E.\,coli$ has a mutation rate of approximately three changes per $10^{10}$ nucleotide pairs each generation, whereas humans exhibit about one change per $10^{10}$ nucleotide pairs per generation.

What selective advantage did the lactase persistence mutation confer to early European populations?

Lactase-persistent individuals had a $6\%$ greater chance of surviving to reproductive age over a span of $3000$ years because milk provided a high-energy, uncontaminated food source available during winter.

How did lactase tolerance prevalence change in Central Europe between 1200 B.C. and today?

Genetic analysis of fallen warriors from a conflict around 1200 B.C. in Germany revealed that only about $12.5\%$ had lactase persistence, whereas today approximately $90\%$ of the population in that region can digest lactose.

How does gene duplication followed by divergence generate multigene families such as the globin genes?

Unequal crossing over duplicates an ancestral gene; while one copy maintains the original function, the second copy accumulates mutations without lethal consequences, allowing it to acquire novel functions or expression patterns.

On which chromosomes are the human $\alpha$-globin and $\beta$-globin gene clusters located?

The $\alpha$-globin gene cluster is located on chromosome $16$, and the $\beta$-globin gene cluster is located on chromosome $11$.

What is a pseudogene and what is its role in evolution?

A pseudogene (indicated by $\psi$) is an inactivated, nonfunctional, and non-expressed copy of a duplicated gene that can serve as raw evolutionary material for future potential functions.

What genetic mechanism led to the evolution of tetraploid species in the frog genus Xenopus?

Duplication of the entire genome occurred when cell division failed following genome replication in the germ line.

What genetic evolutionary process is illustrated in the creation of the modern tissue plasminogen activator (TPA) gene?

Exon shuffling, where distinct exons encoding specialized functional protein domains (such as EGF-like domains, fibronectin finger domains, and plasminogen kringle domains) are recombined through non-homologous recombination within introns.

In Barbara McClintock's maize experiments, how did the Ds (dissociation) element alter kernel color?

Insertion of the $Ds$ element into the $C$ allele broke the gene and caused colorless kernels; occasional excision of $Ds$ restored the functional $C$ allele during development, creating red sectors or spots.

How does the movement mechanism of Class 1 transposable elements (retrotransposons) differ from Class 2 transposable elements (DNA-only transposons)?

Class 1 retrotransposons transcribe their DNA into an RNA intermediate, which is then reverse transcribed into double-stranded DNA by reverse transcriptase before insertion (copy-and-paste); Class 2 transposons are excised as DNA and inserted directly without an RNA intermediate (cut-and-paste).

What are the two most abundant mobile genetic elements in the human genome, and what proportion of the genome do they comprise?

LINE-1 (or L1) elements comprise about $15\%$ of the genome, and Alu sequences comprise about $10\%$ of the genome.

How do Alu elements interact with the ADAR1 enzyme to protect human cells against autoimmunity?

ADAR1 contains a $Z\alpha$ domain that binds Z-DNA formed near Alu elements; it edits double-stranded RNAs produced by Alu repeats, preventing an overproduction of type 1 interferons that would otherwise trigger lupus or inflammatory neurodevelopmental disorders.

What is syncytin, and what is its evolutionary origin?

Syncytin is a placental protein expressed exclusively at the boundary between the placenta and the uterus to facilitate nutrient exchange; it originated from an integrated viral (retroviral) envelope gene.

What is horizontal gene transfer (HGT), and what fraction of the Escherichia coli genome was acquired by this process?

HGT is the transfer of genetic material between different individual organisms (often across species), such as via bacterial conjugation; $E.\,coli$ has acquired approximately one-fifth ($20\%$) of its genome through HGT.

What percentage of the human genome is highly conserved across diverse mammalian species, and what proportion of that conserved portion codes for proteins?

Approximately $4.5\%$ of the human genome is highly conserved in other mammals, and only about one-third ($\sim 1.5\%$ of the total genome) codes for proteins.

Why is the genome of the pufferfish Fugu rubripes only one-tenth the size of the human genome despite containing roughly the same number of genes?

The pufferfish lineage experienced far more extensive sequence loss than gain over evolutionary time, largely shedding repetitive DNA and drastically shortening introns while conserving essential exons.

What gene sequence is universally used to construct the comprehensive phylogenetic Tree of Life across all domains?

The gene encoding the RNA of the small ribosomal subunit (small subunit rRNA).

What are the key numerical statistics of the human genome regarding total size, protein-coding genes, and mean gene size?

• Total genome size: $3.2 \times 10^9$ nucleotide pairs
• Number of protein-coding genes: $\sim 21{,}000$
• Number of non-protein-coding genes: $\sim 9{,}000$
• Mean gene size: $27{,}000$ nucleotide pairs

What criteria are used by computer algorithms to identify potential protein-coding genes within unannotated genomic sequences?

They search for open reading frames (ORFs) consisting of at least $100$ codons that begin with an initiation codon (AUG) and terminate with a stop codon.

How much genetic material do modern European and Asian human populations share with Neanderthals?

Modern humans of European and Asian ancestry share approximately $2\text{--}4\%$ of their genomes with Neanderthals due to interbreeding in Eurasia.

What beneficial allele was introgressed from Denisovans into modern Tibetans?

A variant of the $EPAS1$ gene, which helps red blood cells use oxygen efficiently and enabled high-altitude adaptation $4000\,\text{m}$ above sea level.

What effect did the human-specific duplication of SRGAP2 into SRGAP2C have on brain development?

The truncated $SRGAP2C$ protein dimerizes with and blocks the ancestral $SRGAP2A$ protein, which slows synaptic maturation, increases dendritic spine and synaptic density in the cerebral cortex, and accelerates neuronal migration.

By what percentage do the nucleotide sequences of any two individual humans differ, and how many base-pair differences does this represent?

They differ by approximately $0.1\%$, which equates to roughly $3\text{ million}$ nucleotide differences per genome.

What are the defining genomic characteristics of Single Nucleotide Polymorphisms (SNPs) versus Copy Number Variations (CNVs)?

• SNPs: single base-pair variations present in at least $1\%$ of the population, covering $<1\%$ of the reference genome.

• CNVs: gains or losses of DNA segments ranging from $100\,\text{bp}$ to $3\,\text{Mb}$, covering roughly $29.74\%$ of the reference genome.

Which DNA variations are utilized in forensic DNA fingerprinting and paternity testing?

Short Tandem Repeats (STRs), which vary greatly in length and repeat count among individuals across $13$ standard genomic loci.

Who received the 2018 Nobel Prize in Chemistry for pioneering the directed evolution of enzymes?

Frances H. Arnold.

How did selective pressures alter the frequency of tuskless female elephants in Mozambique's Gorongosa National Park?

During the civil war (1977–1992), intense poaching for ivory caused the proportion of tuskless females to rise from $18\%$ before the war to $50\%$ three decades later; by 2021, when poaching pressure diminished, it fell to $33\%$.

What are the three general classes of cell-surface receptors shown in this diagram?

(A) Ion-channel-coupled receptors (B) G-protein-coupled receptors (GPCRs) (C) Enzyme-coupled receptors

How does dissolved nitric oxide (NO) gas regulate blood vessel diameter?

Endothelial cells release NO, which diffuses across cell membranes directly into adjacent smooth muscle cells, triggering them to relax and causing the blood vessel to dilate.

What distinct physiological outcomes does acetylcholine trigger when binding to different target tissues?

• Heart pacemaker cells: binds GPCRs to open $K^+$ channels, slowing the rate of firing.
• Skeletal muscle cells: binds ion-channel-coupled receptors, triggering rapid muscle contraction.
• Pancreatic cells: stimulates secretion of digestive enzymes.

What molecular mechanism activates a trimeric G protein upon ligand binding to a GPCR?

Ligand binding induces a conformational change in the GPCR, causing the $\alpha$ subunit of the G protein to release GDP and bind GTP, which triggers dissociation of the GTP-bound $\alpha$ subunit from the $\beta\gamma$ complex.

How does cholera toxin produce severe diarrhea at the biochemical level?

It chemically modifies the $\alpha$ subunit of a stimulatory G protein, keeping it locked in an active state that continuously stimulates adenylyl cyclase; the resulting excessive cAMP production causes continuous secretion of water and chloride ions into the gut.

What second messengers are generated by phospholipase C activation, and what are their respective functions?

• Inositol 1,4,5-trisphosphate ($IP_3$): diffuses to the ER membrane and binds to ligand-gated $Ca^{2+}$ release channels, releasing $Ca^{2+}$ into the cytosol.
• Diacylglycerol (DAG): remains embedded in the plasma membrane where, together with cytosolic $Ca^{2+}$, it recruits and activates protein kinase C (PKC).

In rod photoreceptor visual transduction, how much signal amplification occurs after a single rhodopsin molecule absorbs one photon of light?

• $500$ transducin G-protein molecules and $500$ cGMP phosphodiesterases are activated.
• $10^5$ cGMP molecules are hydrolyzed.
• $250$ cation channels close, blocking $10^6\text{--}10^7$ $Na^+$ ions per second from entering for $\sim 1\,\text{second}$.
• Membrane potential hyperpolarizes by $1\,\text{mV}$.

How do receptor tyrosine kinases (RTKs) activate the monomeric GTPase Ras?

Ligand binding causes RTKs to dimerize and autophosphorylate specific tyrosine residues on their cytosolic tails; an adaptor protein binds to a phosphotyrosine and recruits Ras-GEF, which stimulates Ras to exchange bound GDP for GTP.

How does the PI-3-kinase-Akt signaling pathway promote animal cell survival?

Akt phosphorylates the pro-apoptotic protein Bad; this phosphorylation inactivates Bad and causes it to release active Bcl2, which suppresses apoptosis and promotes survival.

What unusual receptor mechanism operates in plant ethylene signaling?

In the absence of ethylene, the unoccupied receptor activates an associated protein kinase that promotes the degradation of a transcription regulator; binding of ethylene inactivates the receptor and kinase, allowing the transcription regulator to stabilize and activate gene transcription.

What are the relative volumes of the three largest intracellular compartments in a typical liver hepatocyte?

1. Cytosol ($54\%$ of total cell volume)

2. Mitochondria ($22\%$ of total cell volume; $\sim 1700$ per cell)

3. Endoplasmic reticulum ($12\%$ of total cell volume)

What are the three distinct mechanisms by which eukaryotic cells transport proteins into membrane-enclosed organelles?

1. Transport through nuclear pores (for the nucleus; transported in folded form)

2. Transport across membranes via protein translocators (for mitochondria, chloroplasts, peroxisomes, and the ER; typically transported unfolded)

3. Transport by vesicles (for transport from the ER along the secretory and endocytic pathways)

Based on this reference table of signal sequences, what specific sequence retains proteins within the lumen of the endoplasmic reticulum?

-Lys-Asp-Glu-Leu-COO- (KDEL).

How does the Ran GTPase cycle maintain directional transport of proteins into the nucleus?

Ran-GEF is exclusively nuclear (producing high Ran-GTP in the nucleus), while Ran-GAP is exclusively cytosolic (triggering GTP hydrolysis to Ran-GDP in the cytosol); nuclear Ran-GTP binds to import receptors, prompting the release of cargo inside the nucleus.

How does the Signal Recognition Particle (SRP) direct a translating ribosome to the ER membrane?

The SRP binds to the ER signal sequence as it emerges from the ribosome and pauses translation; the SRP-ribosome complex then binds to an SRP receptor on the ER membrane and is transferred to a protein translocator.

What are the distinct functions of COPII-coated and COPI-coated vesicles?

• COPII-coated vesicles transport cargo forward (anterograde) from the rough ER to the Golgi cisterna.

• COPI-coated vesicles transport cargo backward (retrograde) from the Golgi cisterna to the ER.

How do Rab proteins and SNARE proteins ensure that transport vesicles dock and fuse with the correct target membrane?

Vesicle Rab proteins are recognized by specific tethering proteins on the cytosolic face of the target membrane (docking); subsequently, a v-SNARE on the vesicle pairs tightly with complementary t-SNAREs on the target membrane to catalyze membrane fusion.

What is the function of dynamin during clathrin-coated vesicle formation?

Dynamin is a GTP-binding protein that forms a ring around the invaginating neck of the coated pit and hydrolyzes GTP to pinch off the vesicle from the membrane.

How does the low pH ($\text{pH} \sim 5.0$) in endosomes and lysosomes facilitate intracellular transport and degradation?

The acidic pH causes endocytosed receptors (such as the LDL receptor) to release their bound cargo for degradation or processing, while providing the optimal acidic environment for hydrolytic enzymes.

What structural hierarchy defines the assembly of intermediate filaments from individual polypeptides?

Two monomeric $\alpha$-helical polypeptides wind together into a coiled-coil dimer; two dimers align in a staggered, antiparallel orientation to form a nonpolar tetramer; eight tetramers bundle laterally and add to the growing rope-like filament.

What cellular defect causes the premature aging disorder Hutchinson-Gilford progeria syndrome?

Defects or mutations in nuclear lamin A, an intermediate filament protein that forms the nuclear lamina meshwork underlying the inner nuclear membrane.

What is the nucleating center for microtubules in animal cells, and which specific protein complex initiates growth?

The centrosome serves as the microtubule-organizing center (MTOC), where $\gamma$-tubulin ring complexes nucleate microtubule growth at their minus ends.

What biochemical event causes dynamic instability in growing microtubules?

When GTP-tubulin dimer addition outpaces GTP hydrolysis, a stable 'GTP cap' forms and the microtubule grows; if GTP hydrolysis catches up and the cap is lost, GDP-tubulin protofilaments peel apart rapidly, causing shrinkage (catastrophe).

How does the motor protein kinesin couple ATP hydrolysis to unidirectional movement along microtubules?

ATP hydrolysis in head 1 loosens its attachment to the microtubule, while ADP release and ATP binding in head 2 changes its neck-linker conformation to propel head 1 forward toward the plus end.

What is the structural basis for the bending movement of eukaryotic cilia and flagella?

A '9 + 2' axoneme arrangement where outer doublet microtubules are interconnected by flexible protein links; when ciliary dynein tries to slide adjacent doublets past each other, the linking proteins convert sliding into bending.

How does the anti-cancer drug Taxol inhibit cancer cell division?

Taxol binds tightly to microtubules and prevents their depolymerization (stabilizing them), which prevents proper mitotic spindle assembly and blocks the cell cycle at the metaphase/anaphase transition checkpoint.

What are the mechanisms of action of the actin-disrupting drugs cytochalasin, latrunculin, and phalloidin?

• Cytochalasin: caps actin filament plus ends, blocking polymerization and triggering minus-end depolymerization.
• Latrunculin: binds free actin monomers, preventing their polymerization.
• Phalloidin: binds tightly along actin filaments, locking them and preventing depolymerization.

Identify the four distinct structural arrangements of actin filaments shown in these cellular diagrams (A through D).

(A) Microvilli (rigid bundles) (B) Stress fibers / contractile bundles (C) Lamellipodia and filopodia at the leading edge of a crawling cell (D) Contractile ring during cell division (cytokinesis)

How does a rise in cytosolic Ca2+ trigger skeletal muscle contraction at the sarcomere?

$Ca^{2+}$ binds to the troponin complex, inducing a conformational change that moves tropomyosin away from the myosin-binding sites on the actin filament, enabling myosin II heads to bind and crawl along actin.