13/08/24

MBIO 2100 Distinguishing features of living

organisms
• High degree of complexity and
Lehninger Principles of Biochemistry
organization.

• Extract, transform, and use energy

CELLS from the environment.

• Capacity for fairly precise self-

Text and figures from Lehninger 3rd – 7th editions
replication while allowing enough
change for evolution.
Barbara H. Zimmermann, Ph.D.

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Biochemical research:
All organisms are remarkably
alike at the chemical and
cellular levels.

In appearance and function, living

organisms differ greatly.

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The Molecular Hierarchy of Structure Cell: The Universal Building Block

• Living organisms are made of cells.

• Simplest living organisms are single-

celled.

• Larger organisms consist of many cells

with different functions.
– Humans contain ~ 1014 cells.

cellular chemical

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Cell: The Universal Building Block

• Most cells are 5 to 100 µm (1 µm What limits the sizes

= 1 x 10-6 m) in diameter. (RBC ~
8 µM) of cells?
• Smallest known cell are ~ 0.3 µm
(mycoplasma) in diameter.

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Lower size limit: Scaling of biosynthesis and metabolism with cell

size.
Determined by the number of Cadart C, Heald R.
molecules required by the cell. Mol Biol Cell. 2022 Aug 1;33(9):pe5. doi: 10.1091/mbc.E21-12-
0627. PMID: 35862496
Upper size limit:
Affected by: Cell size sensing- a one-dimensional solution for a
Accesibility of nutrients three-dimensional problem?
Rishal I, Fainzilber M.
- surface area/volume BMC Biol. 2019; 17:36 PMID: 31035993
- rate of diffusion of solutes The phenomenology of cell size control.
Cell division Schmoller KM.
Curr Opin Cell Biol. 2017;49:53-58.
PMID: 29232627 www.ncbi.nlm.nih.gov
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How does a virus put itself

“... there are physical constraints that limit together?
the ways in which the tool kit of available • Molecular recognition and
biomolecular components can be used to self-assembly.
solve … functional needs
• Geometry and placement of
(i.e., limits on diffusion, catalytic or gene
expression rates, binding specificity, etc.).” forces.
Mol Cell. 49:202-12. (2013)
PMID:23352241

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https://www.youtube.com/watch?v=X- The functions required by the cell determine the cells

8MP7g8XOE architecture.

Arthur J. Olson, Ph.D.

Department of Integrative Structural and Computational
Biology
Scripps Research
La Jolla, California

Demonstration of self-assembly
• Solid printed models of virus components
• Attractive forces between components - magnets Mechanical devices share Molecular devices share
• Kinetic energy - shaking core designs related to core designs related to
their function. their function.
(chairs) (DNA polymerases)
PMID: 23352241

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Classification example: Giant tubeworms

(SO3 2-) sulfide oxidation

The earliest cells according to

arose 3.5 x 109 years source of energy. wikipedia

ago. The earliest cells

were chemotrophs.
These cells were
anaerobic, because Use of light as an
the earth was devoid energy source
occurred after
of O2. evolution of light-
plants

harvesting
pigments.

humans

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Three Distinct Domains of Life Defined by: Three Distinct Domains of Life Defined by:
Cellular and Molecular Differences Cellular and Molecular Differences
BACTERIA Unicellular prokaryote
ARCHAE Unicellular prokaryote
EUKARYOTA Uni/Multicellular eukaryote

Towards a natural system of organisms: proposal for the

domains Archaea, Bacteria, and Eucarya.
Woese CR, Kandler O, Wheelis ML.
Proc Natl Acad Sci U S A. 1990;87:4576-9.
PMID: 2112744
LUCA

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Universal features of living cells.

Plasma membrane
What are universal • Defines periphery (periferia).

features of living cells? • Lipid bilayer held together by

hydrophobic interactions.
• Allows changes in cell shape/size.
• Contains proteins for
transport, signaling, catalysis.
• Impermeable to charged and
polar compounds.

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Universal features of living cells. Universal features of living cells.

Cytoplasm Cytoplasm
Enzymes - catalyze reactions
• aqueous solution
Coenzymes - small compounds essential for some enzyme
• complex composition reactions.

RNA molecules, ribosomes, polysomes - molecules

• gel-like consistency that encode cellular macromolecules, particles of RNA and
protein where protein synthesis occurs.

Metabolites - intermediates in biosynthesis and degradation.

Cytoplasm = the substance between a
cell's membrane (its outside layer) and Granules or droplets of stored fuels - starch, fat.
its nucleus (its core).
Organelles (nonbacterial cells) - membrane-bound
Cytosol = the fluid part of cytoplasm structures containing specialized metabolic machinery.

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Cytoplasm and Cytoskeleton Cytoskeleton maintains

cellular organization
• Cytoplasm is a highly viscous solution
where many reactions take place
• In eukaryotes, the cytoskeleton consists Actin
of microtubules, actin filaments, and Microtubules
intermediate filaments DNA
Bovine
– Cell shape endothelial
– Intracellular organization cells
– Intracellular transport paths
– Cellular movement

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The cytosol is very crowded

“…the cytoplasmic space is
more like a crowded party in a
house full of furniture than a
game of tag (jugar a la lleva) in
an empty field…”

E. coli The physical chemistry of cytoplasm and its influence on

cell function: an update.
bacterial cell Luby-Phelps K.
Mol Biol Cell. 2013;24:2593-6. PMID: 23989722

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Universal features of living cells.

Diffusion and Crowding inside the Cell - ETHZ &
ScienceVisuals/Visualbiotech Nucleus or Nucleoid
• Contains genetic material - DNA
https://www.youtube.com/watch?v=R-wAt7LFDMs and associated proteins.

This video shows the visualization of the simulated • DNA is present in highly
signal transduction process inside the cell. It focuses on compacted form. The densest and
individual molecules and molecular crowding as well as stiffest organelle in eukaryotic
the global view of the cell. The simulation model has cells (PMID:26895141).
been created by the BISON Group at the Swiss Federal
• Nucleus in eukaryotes is
Institute of Technology in Zurich (ETH).
surrounded by a membrane
The video first shows a simulation with 2% of all (= nuclear envelope)
the molecules present in a cell, followed by 100%
• Nucleoid (in prokaryotes) has
molecules present.
no membrane

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Evolution and structure of prokaryotes.

1. Eubacteria
• Well characterized.
ex: Escherichia coli.
• best studied prokaryote.
• inhabits the human intestinal tract
2. Archaebacteria
• Less well characterized.
ex: Methanococcus jannaschi.
• most inhabit extreme environments.
• ancestors of eukaryotic organisms.
http://dsc.discovery.com/.../yst_hotpool_520x420.jpg

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Universal features of bacteria. Universal features of bacteria.

Cell envelope Pili
• Found on the surface of some
• Structure depends on type of
eubacteria (including E. coli)
bacteria
• Play a role in cell adhesion
• Peptidoglycan
- Sugar polymers cross- linked Flagela
by amino acids • One or more found on the
- Provides shape & rigidity surface of motile bacteria
• Plasma membrane. • Thin rigid rods, attached to
- Transporter proteins & rotary motor
respiratory chain proteins

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Universal features of bacteria.

Amazing Flagellum
YouTube, Discovery Science, Dec 5, 2016 Nucleoid
https://www.google.com/search?sca_esv=09c6452bc1fe88ee&sca_upv=1&rlz=1C5C • Contains a single, long
HFA_enCO974CO977&q=bacterial+flagellum+motor&tbm=vid&source=lnms&fbs
=AEQNm0B8dVdIWR07uWWlg1TdKnNtA1cwMugrQsIKmAo5AEZHWRFlUeG circular, compact DNA
LxYlhagMfUatSvHu3MSamP9Qd2SfjyZyVIdPFrZFmdorP0BQX-
5QUvERZ7CgntLysKxPYR85LNkkQ-
molecule.
ODVQlzCBgHDwYGwBEtb1wyzIiqYOAGOFOhRLG73H-
MUdJY1ZFjTgiSsk2gQgTHDHU_Mnn5ewYy4nGfZAENFgsXyYdMtYQ&sa=X&
sqi=2&ved=2ahUKEwiB8Zb7o_KHAxVSbDABHXT0NB4Q0pQJegQIGRAB&biw Plasmids
=1336&bih=624&dpr=2#fpstate=ive&vld=cid:c947ff51,vid:MNR48hUd-Hw,st:0
• Smaller, circular DNA
Propulsa la bacteria 20 longitudes (bacterianas) por molecules
resistance to toxins and
Segundo.
antibiotics
Extrapolar a escala humana: 20 longitudes corporales
por segundo (1,8 m humano -> 36 metros/seg)

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How did eukaryotic cells evolved from Evolution of Eukaryotes through Endosymbiosis
prokaryotes ?
1. Cells acquired more DNA. Cells began to
store DNA in chromosomes (= complexes of
DNA and protein).
2. Cells became larger. Systems of intracellular
membranes developed.
3. Cells enveloped aerobic or photosynthetic
bacteria to form endosymbiotic associations
that became permanent.
• mitochondria evolved from aerobic bacteria.
• chloroplasts evolved from anaerobic bacteria.

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Data supporting the endosymbiotic theory

1. Mitochondria and chloroplasts are semiautonomous*.
What evidence supports DNA, ribosomes, and machinery to synthesize DNA.

this theory of the origin 1. Organelle DNA sequences are more similar to bacterial
sequences than eukaryotic sequences
of mitochondria and Mitochondrial: aerobic bacteria
Chloroplast: cyanobacteria

chloroplast organelles? 3. Replication of organelles is similar to bacterial cell

division (they contain circular DNAs and divide by fission).
*neither organelle contains all the genes it requires. Most
organelle genes are coded for by nuclear DNA, the proteins are
synthesized in the cytosol and then imported into the
organelle.

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Do bacteria have organelles? Do bacteria have organelles?

“Bacterial microcompartments
are functional analogues of the Enzymes
organized along
lipid-bound organelles of the inside of the
eukaryotes. They enclose chemical shell
reactions that benefit from being Protein shell
separated from the cytosol.” encapsulating
enzymes.
Bacterial microcompartments.
The shells of BMC-type microcompartment organelles in bacteria.
Kerfeld CA, Aussignargues C, Zarzycki J, Cai F, Sutter M.
Yeates TO, Jorda J, Bobik TA.
Nat Rev Microbiol. 2018;16:277-290. PMID: 29503457
J Mol Microbiol Biotechnol. 2013;23:290-9. PMID: 23920492

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Viruses Viruses
• Exist in 2 states.
• Supermolecular complexes that outside the host:
replicate themselves in appropriate nonliving particles, virions.
host cells. inside the host:
intracellular parasite, use the
cell’s machinery to replicate.
• Nucleic acid (DNA or RNA)
• Specific for their host cells.
surrounded by a protective shell
• Some integrate their genetic material into host
made of protein, or in some cases chromosome, which is replicated with host
membranes. DNA. Other cause host cell lysis.

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Examples of virus Examples of virus

Human immunodeficiency
Human polio virus (type 2) virus (HIV) shown escaping
–––––––––> from an infected T
lymphocyte of the immune
Vaccination programs system in an electron
micrograph. –––––––––>
have nearly eliminated
polio.
Pre-exposure prophylaxis (or PrEP) is when people at very high risk for HIV
take daily medicine to prevent HIV.
Coronavirus: 30 kb RNA Studies have shown that PrEP reduces the risk of getting HIV from sex by about 99% when
Polio virus: 7.5 kb RNA taken daily. Among people who inject drugs, PrEP reduces the risk of getting HIV by at least
74% when taken daily.
E. coli genome: 5 x 103 kb DNA tenofovir (AMP analog) and emtricitabine (cytidine analog, nucleoside)
Human genome: 3 x 106 kb DNA https://www.cdc.gov/hiv/basics/prep.html

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Examples of virus
WHAT’S NEW??? Huge viruses
that infect single
cell organisms Bacteriophage = a virus
Giant Viruses (2003) such as
Acanthamaebas that infects bacterial cells
and
Viruses that Bacteriophage sX174 à
Virophages (2008) are parasites
of Giant
The Expanding Family of Virophages. Viruses
Bekliz M, Colson P, La Scola B.
Viruses. 2016;8. pii: E317. PMID: 27886075

Virophages and Their Interactions with Giant Viruses and Host Cells.
Sobhy H
Proteomes. 2018;6. pii: E23. PMID: 29786634

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Do you think
bacteriophages
could be useful?

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Engineered
bacteriophages for
treatment of a patient
with a disseminated
drug-resistant
Mycobacterium
abscessus.
Dedrick et al.
Nat Med. 2019;
25:730-733. PMID:
31068712
https://seaphages.org/ Graham Hatfall
University of Pittsburgh
Bank of 15,000 phages
Many are from the SEA-PHAGES program
• 150 institutions
Cell. 2023 Jan 5;186(1):17-31. • Undergraduate research projects
doi: 10.1016/j.cell.2022.11.017 • Howard Hughes Medical Institute
https://www.genengnews.com/insights/set-phages-to-
PMID: 36608652 kill/?utm_medium=newsletter&utm_source=GEN+Daily+News+Highlights&utm_content=01&utm_campaign=GEN
+Daily+News+Highlights_20200120&oly_enc_id=1794I4328467J2F

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PMID: 31068712
• Two cystic fibrosis patients in UK
infected with drug resistant strains
of Mycobacterium abscessus.
• Researcher sent the M. abscessus
strains to the US to see if any
phages in the phage bank could kill the bacteria.
• They found lethal phages for the strains
• One patient died before they could do phage therapy.
• The second patient was treated intervenously for 6
months with a cocktail of 3 phages, and recovered

https://www.genengnews.com/insights/set-phages-to-
kill/?utm_medium=newsletter&utm_source=GEN+Daily+News+Highlights&utm_content=01&utm_campaign=GEN
+Daily+News+Highlights_20200120&oly_enc_id=1794I4328467J2F

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