Welcome to Curiosity Minisodes—where we tackle high-order questions from high-yield topics in 10 minutes or less.

Today, we’re digging into biological classification.

Hosted by Michael McNeil.

Our cover art for this episode is based on the watercolor illustration "Last Universal Common Ancestor" by David Goodsell. RCSB Protein Data Bank. doi: 10.2210/rcsb_pdb/goodsell-gallery-035

Follow Curiosity on Instagram (www.instagram.com/newwaytowonder) and YouTube (youtube.com/@curiosityeducation) and share your thoughts and burning science questions with our host by emailing contact@mdmcneil.com.

Why does taxonomy matter—and what can it teach us about our place among life on Earth? In Part 1 of our two-part exploration of eukaryotic cells, we unpack the history of classification, from Aristotle to Linnaeus to us, and take a closer look at how emergence supports the intricacy and complexity of our experience of life.

Hosted by Michael McNeil. Special thanks to T. Aleman, A. Graulau, J. Ishimwe, and J. Reid.

Our cover art for this episode is based on the prints of the biologist Ernst Haeckel.

Follow Curiosity on Instagram (www.instagram.com/newwaytowonder) and YouTube (youtube.com/@curiosityeducation) and share your thoughts and burning science questions with our host by emailing contact@mdmcneil.com.

0:00 - Part 0: Introduction

1:50 - Part 1: Biological Emergence

7:07 - Part 2: History of Biological Classification

25:13 - Part 3: Eukaryotic Taxonomy

Earth is home to an estimated 10 million forms of life, but we can't see most of them with our own eyes. In today's episode, we'll take a peek behind the curtain. We'll explore the bizarre structures, lethal defenses, and fascinating mating habits of bacteria. And we'll finally get introduced to archaea, the newest, oddest, and least understood members of the family tree.

0:00 - Part 0: Introduction

5:56 - Part 1: General Prokaryotic Features

• Prokaryotes vs. Eukaryotes
• Morphological Diversity
• Cell Wall Characteristics
• Cell Membranes, Lipopolysaccharide, and Lipid A

26:02 - Part 2: Gram Staining

• The Gram Stain Protocol
• Gram Staining Insights

34:23 - Part 3: Additional Prokaryotic Structures

• Capsules and Tonicity
• Endospores
• Fimbriae
• Pili
• Non-Flagellar Locomotive Structures
• Flagella and Taxis

51:30 - Part 4: Prokaryotic Growth and Metabolism Considerations

• Autotrophs, Heterotrophs, Chemotrophs, and Phototrophs
• Aerobes vs Anaerobes

53:32 - Part 5: Prokaryotic Reproduction and Gene Exchange

• Binary Fission
• Transduction
• Transformation
• Conjugation

1:04:34 - Part 6: Bacteria vs Archaea

• The First Archaebacteria
• Difficulties in Studying Archaea

References + Further Reading

- Bardy, S. L., Ng, S. Y. M., & Jarrell, K. F. (2003). Prokaryotic motility structures. Microbiology, 149(2), 295-304. https://doi.org/10.1099/mic.0.25948-0

- Casson, H. N. (1911). The history of the telephone. A. C. McClurg.

- Clark, M. A., Douglas, M., & Choi, J. (2018). Biology 2e. OpenStax.

- Fagan, R. P. & Fairweather, N. F. (2014). Biogenesis and functions of bacterial S-layers. Nature Reviews Microbiology, 12, 211-222. https://doi.org/10.1038/nrmicro3213

- Gao, S. ... & Wang, Y. (2024). Bacterial capsules: Occurrence, mechanism and function. NPJ Biofilms and Microbiomes, 10(21). https://doi.org/10.1038/s41522-024-00497-6

- Hersh, D. S. ... & Kim, A. J. (2016). Evolving drug delivery strategies to overcome the blood brain barrier. Current Pharmaceutical Design, 22(9), 1177-1193. http://dx.doi.org/10.2174/1381612822666151221150733

- Lambert, P. A. (2002). Cellular impermeability and uptake of biocides and antibiotics in Gram-positive bacteria and mycobacteria. Journal of Applied Microbiology, 92(s1), 46S-54S. https://doi.org/10.1046/j.1365-2672.92.5s1.7.x

- Mole, B. (2015). Bacteria staining method has long been misexplained. Science News. https://www.sciencenews.org/article/bacteria-staining-method-has-long-been-misexplained

- Nath, D. (2008). The prokaryotic cytoskeleton. Nature Reviews Molecular Cell Biology, 9(Suppl 1), s19. https://doi.org/10.1038/nrm2582

- National Geographic Society. (2023). Feb 1, 1884 CE: First publication of the Oxford English Dictionary. https://education.nationalgeographic.org/resource/first-publication-oxford-english-dictionary/

- Pallin, D. J., & Wright, J. (2022). MCAT: Biology review (3rd ed.). The Princeton Review.

- Pöhl, S. ... & Thanbichler, M. (2024). An outer membrane porin-lipoprotein complex modulates elongasome movement to establish cell curvature in Rhodospirillum rubrum. Nature Communications, 15(7616). https://doi.org/10.1038/s41467-024-51790-z

- Richard, S. (2020). How Helicobacter stays helical. Fred Hutch Cancer Center. https://www.fredhutch.org/en/news/center-news/2020/01/salama-helicobacter-pylori-shape.html

- Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V., & Orr, R. B. (2021). Campbell: Biology (12th ed.). Pearson.

- Woese, C. R. & Fox, G. E. (1977). Phylogenetic structure of the prokaryotic domain: The primary kingdoms. Proceedings of the National Academy of Sciences, 74(11), 5088-5090. https://doi.org/10.1073/pnas.74.11.5088

Correction

- At 34:49, Michael misspoke. Capsules connect to peptidoglycan in Gram-positive bacteria and to the outer cell membrane in Gram-negative bacteria, not the other way around.

Special Thanks

- University of Wisconsin-Madison

- U.S. National Park System

- T. Aleman, J. Ishimwe, J. Wilson, and A. Graulau

What is life? What makes something alive? And how do viruses fit into those criteria?

In this episode, we'll explore the structure, diversity, and behavior of viruses. We'll also discuss the pathology of subviral particles like prions and viroids.

0:00 - Part 0: Introduction

2:29 - Part 1: The History of Viral Discovery

• Viral Size
• Adolf Mayer and the Tobacco Mosaic Virus
• Dmitri Ivanovsky and the Filter Experiment
• Martinus Beijerinck and the 'Contagium Vivum Fluidum'

8:40 - Part 2: Viral Structure

• Basic Virion Structure
• Structural Diversity
• Bacteriophage Structure

13:00 - Part 3: Bacteriophages

• Attachment and Penetration
• The Lytic Cycle
• Regulation of Infection Sequence
• The Lysogenic Cycle
• Lysogenic Conversion

28:06 - Part 4: Bacterial Defenses

• Bacterial Capsules
• Binding Failure
• Superinfection Exclusion
• Abortive Infection
• Restriction Enzymes
• The CRISPR/Cas9 System

37:44 - Part 5: Animal Viruses

• Variations in the Lytic Approach
• Variations in Lysogenic Terminology

42:38 - Part 6: Animal Virus Classification

• The ICTV System
• Baltimore Classification
• Retroviruses

53:26 - Part 7: Prions

• Protein Infections
• Transmissible Spongiform Encephalopathies

57:57 - Part 8: Viroids

• Viroid Structure
• Viroid Pathology

References + Further Reading

- Abedon, S. T. (2012). Bacterial ‘immunity’ against bacteriophages. Bacteriophage, 2(1), 50-54. https://doi.org/10.4161/bact.18609

- Bucher, M. J. & Czyż, D. M. (2024). Phage against the machine: The SIE-ence of superinfection exclusion. Viruses, 16(9), 1348. https://doi.org/10.3390/v16091348

- Cheng, C. & Kirkpatrick, M. (2021). Molecular evolution and the decline of purifying selection with age. Nature Communications, 12(2657). https://doi.org/10.1038/s41467-021-22981-9

- Clark, M. A., Douglas, M., & Choi, J. (2018). Biology 2e. OpenStax.

- Dutchen, S. (2022). The good that viruses do. Harvard Medicine. https://magazine.hms.harvard.edu/articles/good-viruses-do

- Elena, S. F., Dopazo, J., Flores, R., Diener, T. O., & Moya, A. (1991). Phylogeny of viroids, viroidlike satellite RNAs, and the viroidlike domain of hepatitis delta virus RNA. Proceedings of the National Academy of Sciences, 88(13), 5631-5634. https://doi.org/10.1073/pnas.88.13.5631

- Feiner, R., Argov, T., Rabinovich, L., Sigal, N., Borovok, I., & Herskovits, A. A. (2015). A new perspective on lysogeny: Pro-phages as active regulatory switches of bacteria. Nature Reviews Microbiology, 13, 641-650. https://doi.org/10.1038/nrmicro3527

- Gostimskaya, I. (2022). CRISPR-Cas9: A history of the discovery and ethical considerations of its use in genome editing. Biochemistry (Moscow), 87, 777-788. https://doi.org/10.1134/S0006297922080090

- Lopatina, A., Tal, N., & Sorek, R. (2020). Abortive infection: Bacterial suicide as an antiviral immune strategy. Annual Review of Virology, 7(1), 371-384. https://doi.org/10.1146/annurev-virology-011620-040628

- Pallin, D. J., & Wright, J. (2022). MCAT: Biology review (3rd ed.). The Princeton Review.

- Prussin, A. J., Garcia, E. B., & Marr, L. C. (2016). Total virus and bacteria concentrations in indoor and outdoor air. Environmental Science & Technology Letters, 2(4), 84-88. https://doi.org/10.1021/acs.estlett.5b00050

- Rostøl, J. T. & Marraffini, L. (2019). (Ph)ighting phages: How bacteria resist their parasites. Cell Host & Microbe, 25(2), 184-194. https://doi.org/10.1016/j.chom.2019.01.009

- Scheckel, C. & Aguzzi, A. (2018). Prions, prionoids and protein misfolding disorders. Nature Reviews Genetics, 19, 405-418. https://doi.org/10.1038/s41576-018-0011-4

- Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V., & Orr, R. B. (2021). Campbell: Biology (12th ed.). Pearson.

Correction

- At 16:55, Michael misspoke. He said "lysosome" but meant to say "lysozyme." Both these structures carry out reactions that degrade cellular components, but bacteriophages specifically mobilize the lysozyme (in this context) to degrade the bacterial cell wall.

How do cells know when to turn some genes on or off? Or which genes to activate when their environments change?

In today's episode, we'll do a deep dive into the three levels of gene regulation, exploring how prokaryotes and eukaryotes modulate their DNA, RNA, and proteins in real time to meet real needs.

Part 1: DNA Regulation

- Chromatin and Histones

- Histone Acetylation and Deacetylation

- Histone Phosphorylation and Dephosphorylation

- Histone Methylation and Demethylation

- Ubiquitination and SUMOylation

- DNA Methylation

- Genomic Imprinting

- X Chromosome Inactivation

- Gene Dosage (Copy Number Variations and Aneuploidy)

Part 2: Prokaryotic RNA Regulation

- Inducible and Repressible Operons

- The Lac Operon

- The Trp Operon

Part 3: Eukaryotic RNA Regulation

- Transcription Factors and Enhancers

- RNA Translocation

- mRNA Surveillance

- RNA Interference, siRNAs, and miRNAs

Part 4: Protein Regulation

- Post-Translational Modifications

Correction: At 24:27, Michael incorrectly described the meaning of the term "CpG islands." "CpG" does stand for "cytosine-phosphodiester-guanine" or "cytosine-phosphate-guanine," but this refers to the bonds between cytosines and guanines in the backbone of these regions along the same strand, not the complementary base-pairing of cytosine and guanine on opposite strands. Recall that complementary base-pairing occurs via hydrogen bonds, not phosphodiester ones. CpG islands are notable for containing many cytosines and guanines in close proximity.

Correction: At 54:00, Michael misspoke. He said "decade" but should have said "century."

How do cells convert the instructions of messenger RNA into proteins? What are the famous "gene machines" actually made of? And what happened when a World War II soldier suddenly ended up with a disease no one could cure?

In today's episode, we'll answer all these questions⎯and so many more⎯as we explore the last stage of the Central Dogma: translation.

Part 1: tRNA Structure

• The RNA Tie Club
• The Adaptor Hypothesis and Transfer RNA (tRNA)
• The Five Components of tRNA
• The 2D and 3D Structures of tRNA

Part 2: The Wobble Hypothesis

• Protein-Coding (Sense) vs. Non-Protein-Coding (Nonsense) Codons
• The Start Codon
• The Stop Codons
• Traditional Codon-Anticodon Pairing
• Wobble Pairing

Part 3: Amino Acid Activation (tRNA Loading)

• Reaction Coupling
• Formation of Aminoacyl-AMP
• Pyrophosphate Hydrolysis
• Formation of Aminoacyl-tRNA
• Aminoacyl-tRNA Synthetases

Part 4: The Ribosome

• Ribosomal RNA (rRNA)
• Understanding Svedberg Units
• The 70S and 80S Ribosomes
• The Role of the Nucleolus
• RNA Polymerases I, II, and III
• The A, P, and E Sites

Part 5: Prokaryotic Translation

• Polyribosomes
• Polycistronic mRNA
• The Shine-Dalgarno (SD) Sequence
• Initiation: Initiation Factors, Initiator tRNA, Formylmethionine, and the Translation Initiation Complex
• Elongation: Elongation Factors and the 3-Part Cycle
• Termination: Release Factors and Dissociation

Part 6: Eukaryotic Translation

• Monocistronic mRNA
• The 5' Cap Binding Site
• The Kozak Sequence
• Basics of Initiation, Elongation, and Termination
• Cap-Dependent Translation
• Internal Ribosome Entry Sites (IRES) and Cap-Independent Translation
• Post-Translational Modifications

References

• Clark, M. A., Douglas, M., & Choi, J. (2018). Biology 2e. OpenStax.
• Pallin, D. J., & Wright, J. (2022). MCAT: Biology review (3rd ed.). The Princeton Review.
• Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V., & Orr, R. B. (2021). Campbell: Biology (12th ed.). Pearson.

Further Reading

• Bilbray, B. P. (2012). Antibiotic treatments over the past century. Congressional Record.
• Crick, F. (1955). On degenerate templates and the adaptor hypothesis: A note for the RNA Tie Club. NIH.
• Crick, F. (1958). On protein synthesis. Wellcome Collection.
• Dole, B. (2005). One soldier's story. HarperCollins Publishers.
• Ramakrishnan, V. (2018). Gene machine: The race to decipher the secrets of the ribosome. Basic Books.

How is DNA converted into RNA?

In this episode, we continue our conversation in molecular biology by focusing on the first stage of the Central Dogma: transcription. We explore this process in tremendous detail⎯from the unique proteins involved in initiation, elongation, and termination to the many ways transcription differs between prokaryotes and eukaryotes.

Part 1: Overview

- Transcription

- RNA vs. DNA

- Prokaryotic and Eukaryotic RNA Polymerases

Part 2: Initiation

- The Prokaryotic Promoter: the -35 Sequence and the Pribnow Box

- The Eukaryotic Promoter: the TATA Box

- Open and Closed Complexes

- The Preinitiation Complex

- Transcription Factors

Part 2: Elongation

- The Transcription Bubble

- The Template and Non-Template Strand

Part 3: Termination

- Prokaryotic Termination: Rho-Dependent and Rho-Independent

- Eukaryotic Termination and the Polyadenylation Signal Sequence

- Processivity

Part 4: Eukaryotic Post-Transcriptional Modification

- Introns, Exons, and Splicing

- Alternative Splicing

- The 5' Cap

- The Poly(A)-Tail

What does DNA do, exactly? And how does it do it?

In this episode, we see how DNA's structure informs its role as a storage molecule for genetic information. We review the major experiments and discoveries that informed our present understanding of basic molecular biology. We also explore the many roles of proteins in the cell and how DNA utilizes a special genetic code to relay the instructions for protein synthesis.

Part 1: Discovering the Role of DNA

- The Functions of Proteins

- The Griffith Experiment and Bacterial Transformation

- The Avery-MacLeod-McCarty Experiment

- The Hershey-Chase Experiment

- Basics of the Genetic Code

Part 2: The Central Dogma

- The Role of Messenger RNA

- Overview of the Central Dogma

- Caveats to the Central Dogma