The Making of the Fittest: The Birth and Death of Genes (Video Transcript)

The Birth and Death of Genes

• Notothenioids (Antarctic notothenioids) evolved anti-freeze proteins allowing survival in near-freezing waters; icefish later evolved without red blood cells/hemoglobin.

• Notable timeline: Drake Passage opened ~34 million years ago, cooling surrounding waters and driving antifreeze evolution; icefish lineage diverged in this context.

• Mechanism highlighted: inventing something new from old genetic material via gene duplication and mutation.

• Key example: antifreeze proteins formed when an ancestral gene was duplicated; one copy remained, the other acquired mutations to yield a new function.

• In icefish, a second major change occurred: elimination of red blood cells and hemoglobin, enabling survival in extremely cold water despite loss of hemoglobin.

• Conclusion: evolution often proceeds by both invention (new functions) and loss (gene deaths); DNA records these changes over deep time.

Antifreeze Genes, Duplication, and Pseudogenes

• Gene duplication creates raw material for novelty; duplicated copies can diverge and acquire new functions (neofunctionalization).

• Some duplicated genes become nonfunctional (pseudogenization); others partition original functions (subfunctionalization).

• Notothenioids provide a classic example of invention from old code:

  • Notothenioid antifreeze genes arose from a duplicated gene that mutated to a new function.

  • Icefish globin genes show a different fate: a mutation wrecked the red blood cell gene; the gene became nonfunctional and remained as a fossilized remnant in DNA.

• Pseudogenes can persist and influence regulation (e.g., endo-siRNAs; regulatory roles) and can originate via duplication or retrotransposition (processed pseudogenes).

• De novo gene formation from noncoding DNA also contributes new genes; some are male-germline biased or X-linked.

• Mechanisms of new gene origination include duplication, transposable element domestication, lateral gene transfer, gene fusion/fission, and de novo origination.

• Practical takeaway: genomes are dynamic; gene birth and gene death shape adaptation and speciation.

Mechanisms of Gene Origination and Fates

• Gene duplication: whole-genome, segmental, tandem; retroposition; transposable elements can contribute to new genes.

• Transposable Element (TE) domestication: TE proteins co-opted for host functions (immune systems, sensing, etc.).

• Lateral (horizontal) gene transfer: gene movement between species; common in bacteria, occurs between organelles and nuclear genomes.

• Gene fusion/fission: creation of new genes via combining or splitting transcripts.

• De novo origination: entirely new genes from noncoding DNA.

• Fates of duplicates: nonfunctionalization (pseudogene); neofunctionalization (new function); subfunctionalization (partition of original function); maintenance of both for increased dosage or regulatory versatility.

• Implication: gene duplication and loss drive genome evolution and can contribute to speciation and adaptation.

Gas Exchange and Diffusion: Principles to Practice

• Gas exchange relies on diffusion; rate governed by Fick’s law: Q= rac{D A}{L}(P1-P2) where

  • Q = rate of gas transfer, D = diffusion coefficient, A = surface area, L = diffusion distance, P1-P2 = partial pressure gradient.

• Media differences:

  • Air: high O2 partial pressure, low density; O2 concentration ~210 ml/L; low viscosity.

  • Water: lower O2 concentration (~7 ml/L at 20°C), high density and viscosity; diffusion is harder, so large surface areas are needed.

• Notable gas exchange structures:

  • Gills (bony fish): water flows unidirectionally; lamellae maximize surface area and minimize diffusion distance; lamellae facilitate countercurrent exchange.

  • Lungs (mammals): alveolar surface area; ventilation (breathing) increases P1 (air on surface) and perfusion (blood flow) maintains P2 gradient.

• Exchange efficiency: countercurrent flow maintains a gradient along the entire exchange surface, enabling more complete O2 extraction than concurrent flow.

• Oxygen transport and loading/unloading:

  • Hemoglobin (Hb) binds O2 in lungs and releases in tissues; Hb-O2 affinity shifts with pH, CO2, temperature (Bohr effect).

  • Oxygen dissociation curve: left shift = higher affinity (more saturation at given PO2); right shift = lower affinity.

• Hemoglobin and notothenioids:

  • Icefish lack hemoglobin or have greatly reduced Hb; compensation via cutaneous O2 uptake and special circulatory adaptations.

Oxygen Transport, Hb Affinity, and the Bohr Effect

• Oxygen dissociation curve basics:

  • Higher Hb-O2 affinity (left shift) when CO2 is low, pH high, and temperature is low.

  • Lower Hb-O2 affinity (right shift) when CO2 is high, pH is low (acidic), and temperature is high.

• Bohr effect: in tissues producing CO2 (lower pH), Hb releases more O2; in lungs (higher pH), Hb binds O2 more readily.

• Clinical/physiological relevance: variations in PO2, pH, temperature adjust oxygen delivery to tissues depending on metabolic demand.

Temperature Regulation and Homeostasis

• Endotherms vs. Ectotherms:

  • Endotherms maintain relatively constant body temperature via metabolic heat production (mammals, birds).

  • Ectotherms rely on external environmental heat sources; body temperature tracks surroundings.

• Metabolic rate differences:

  • Endotherms maintain higher baseline metabolic rates; in cold environments, metabolic heat production rises in endotherms but falls in ectotherms.

• Thermoregulation mechanisms:

  • Countercurrent heat exchange networks reduce heat loss in limbs.

  • Behavioral strategies (sun/shade shuttling) regulate body temperature.

  • Brown fat in infants generates heat without shivering.

• Homeostasis and feedback:

  • Negative feedback returns a system toward a set point (e.g., thermoregulation).

  • Positive feedback reinforces a process (e.g., blood clotting).

  • Examples: hypothalamic control of body temperature; fever as a regulatory response.

The Surface Area to Volume Constraint and Size-Related Adaptations

• SA/V principle: higher surface-area-to-volume ratio in small or thin objects supports more efficient exchange with the environment; larger/thicker objects have lower SA/V, limiting diffusion.

• Evolutionary responses:

  • Small cells or flat/expanded surfaces (flat leaves vs. cactus spines) adjust exchange surfaces.

  • Larger organisms rely on specialized organs (gills, lungs, circulatory systems) to enhance effective surface area and maintain homeostasis.

• Core idea: diffusion limits drive the evolution of organism shape, structure, and internal transport systems.

Evolution of Genes and Genomes

• Core concepts:

  • Genes can be born and die; genomes are dynamic.

  • Mechanisms generating new genes: gene duplication, TE domestication, lateral gene transfer, gene fusion/fission, and de novo origination.

  • Duplications can lead to neofunctionalization, subfunctionalization, or pseudogenization; both copies can be retained for dosage or regulatory reasons.

• Notable examples:

  • Antifreeze proteins in Antarctic icefish arose via duplicated gene that mutated to a new function.

  • Arctic cod antifreeze proteins formed de novo from noncoding DNA; Antarctic icefish antifreeze proteins arose from a duplicated gene (not identical paths).

  • Pseudogenes can persist and regulate genes via RNA-based mechanisms (endo-siRNAs, microRNAs) and can originate from processed or nonprocessed copies.

• Molecular clock and selection:

  • Molecular clock hypothesis: DNA/protein sequences evolve at relatively constant rates; genetic differences approximate time since divergence when calibrated with fossils or known events.

  • Signatures of selection in DNA sequences use ratios of nonsynonymous (N) to synonymous (S) substitutions (N/S):

  • N/S = 1: neutral

  • N/S > 1: positive selection

  • N/S < 1: purifying (negative) selection

The Molecular Clock and Phylogeny

• Molecular clock applications:

  • Date divergence times between species using neutral regions; requires calibration.

  • HIV-1 evolution studies have dated origins and divergence times using clock-like behavior.

• Phylogeny basics:

  • Phylogenetic trees depict evolutionary relationships; nodes indicate speciation events; roots denote common ancestors.

  • Clades (monophyletic groups) are groups consisting of a common ancestor and all its descendants.

• Ancestral vs derived traits:

  • Ancestral: present in a common ancestor.

  • Derived: trait differs from the ancestor in a descendant.

• Homologous vs analogous traits:

  • Homologous: shared ancestry; used to infer relationships.

  • Analogous (convergent): similar features due to similar selection pressures, not common ancestry.

• Species concepts:

  • Morphological (phenotypic similarity)

  • Lineage/Phylogenetic (branch-based)

  • Biological (interbreeding and reproductive isolation)

  • No single concept fits all organisms; use context-appropriate concept (e.g., fossils -> morphological; bacteria -> lineage/New genes; sexually reproducing animals -> biological).

• Speciation concepts:

  • Allopatric: geographic isolation drives divergence; vicariance vs dispersal.

  • Sympatric: divergence with gene flow occurring in the same area; often via polyploidy or strong disruptive selection.

  • Prezygotic barriers (habitat, temporal, behavioral, mechanical, gametic).

  • Postzygotic barriers (hybrid inviability, infertility, breakdown).

• Polyploidy and speciation:

  • Autopolyploidy: same species doubles chromosome number, often leading to instant reproductive isolation.

  • Allopolyploidy: hybridization between species followed by chromosome doubling.

Population Genetics: Drift, Bottlenecks, Founder Effect, and Gene Flow

• Genetic drift: random fluctuations in allele frequencies due to sampling error; stronger in small populations and can reduce genetic variation.

• Bottleneck effect: severe reduction in population size causes loss of genetic diversity and shifts allele frequencies.

• Founder effect: new population established by a small subset of individuals, leading to different allele frequencies from the source population.

• Gene flow (migration): transfer of alleles between populations; tends to homogenize populations and can counter local adaptation.

• Practical examples:

  • Capybaras: higher nonsynonymous substitution rates in some comparisons may reflect drift in large populations; caveats include generation time differences.

  • Amish founder effect: increased homozygosity for recessive alleles (e.g., Ellis-van Creveld syndrome).

• Implications: drift, bottlenecks, founder effects, and gene flow shape genetic variation and can influence adaptation and speciation trajectories.

Skin Color: UV Radiation, Folate, and Vitamin D Trade-Offs

• Skin color is polygenic, with estimates of multiple genes (6 primary genes, potentially up to ~169 genes).

• Selective pressures vary with latitude due to UV radiation:

  • High UV: selection for darker skin to protect folate; darker pigmentation reduces folate destruction.

  • Low UV: selection for lighter skin to enhance vitamin D production.

• The folate–vitamin D trade-off helps explain geographic variation in skin color and supports positive/negative selection dynamics on pigmentation alleles.

Quick Reference Equations and Concepts

• Fick’s law of diffusion (gas exchange): Q= rac{DA}{L}(P1-P2)

• Oxygen affinity shifts (Bohr effect): more CO2 or lower pH lowers Hb-O2 affinity; higher pH and lower CO2 raise Hb-O2 affinity.

• Molecular clock concept: genetic differences ∝ time since divergence; requires calibration with independent data.

• N/S substitutions as a test for selection: ext{N/S}= rac{ ext{nonsynonymous substitutions}}{ ext{synonymous substitutions}}

  • N/S > 1 indicates positive selection; N/S < 1 indicates purifying selection.

• Gene fate after duplication: nonfunctionalization (pseudogene), neofunctionalization (new function), subfunctionalization (partitioning function), maintenance (dosage/duplication).

Exam-ready Takeaways

• Evolution uses both invention (new functions) and loss (gene death); not all changes are optimal, but they are workable in changing habitats.

• Antifreeze proteins in Notothenioids illustrate rapid adaptation via gene duplication and modification; icefish show an extreme case of gene loss (hemoglobin).

• Diffusion and surface area constraints shape how organisms exchange gases; countercurrent exchange maximizes gas transfer efficiency.

• Temperature regulation involves both physiological (endothermy) and behavioral strategies; feedback mechanisms (negative/positive) govern homeostasis.

• Species concepts are context-dependent; understand strengths/limits of morphological, lineage, and biological concepts for different data types.

• Populations evolve under drift, gene flow, and selection; bottlenecks and founder effects can reshape genetic variation and influence adaptation.

• Skin color variation reflects polygenic inheritance and latitude-dependent selective pressures balancing vitamin D and folate needs.