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THE FRONTIERS OF LIFE
LECTURES IN PHYSIOLOGY AND DEVELOPMENT IN THE LIGHT OF
EVOLUTION
David Barrington, 2008
Most of what I want to teach in this fourth portion of BCOR 12 relates one way or
another to activity at cell membranes, especially as a frontier between the inside and
outside of cells, so we have both pursued course development with this mindset.
I will use the frontier theme throughout, with the frontiers including those 1) between
cells of the same organism, 2) between cells and the environment, and 3) between cells of
different individuals (mostly of the same species). In the lecture sequence, this whole
body of ideas is preceded by two introductory segments, the first on the origin of the
phsopholipid bilayer and the second on the origin or multicellularity. The origin of the
bilayer relates directly to the origin of life, which I find compelling in its relevance to
thinking about origins in general. The origin of multicellularity was required for
interactions between cells of the same organism to begin in the first place. These same
interactions relate to the contacts between cells of unrelated species (self and non-self).
The specialization that comes with multicellularity in turn implies a developmental
program, which provides me an avenue to the very exciting field of development and
evolution. Because evolution is my own research discipline, I will cast everything
possible in the context of evolutionary history. The role of the environment in shaping
evolutionary history allows me to bring ecological factors, which completes the progress
of this syllabus towards a fully integrated approach to biology.
I. The Membrane Frontier: the cell membrane
In this first part of my lecture, I review membrane structure in function as a way to
introduce the most critical frontier in biology. The structural and functional ideas that we
introduce here return again and again as we consider the diversity of topics related to the
physiology and development of animals and plants.
A. Membrane Structure
1. Amphiphilic phospholipids self assemble into envelopes that are barriers to polar
molecules.
2. The fatty acids give them their non-polar character; the phosphate and R groups
such as choline give them their polar character.
3. The membrane envelope is fluid – laterally but not flip-flop (tangentially but not
radially).
B. Membrane Proteins and their Functions
1. Proteins are positioned in the membrane by the location of their non-polar amino
acids.
2. The proteins are also fluid.
3. Membrane protein functions fall in six classes (our examples in parentheses):
a. Transport (channels and pumps)
b. enzymatic activity
c. signal transduction (tyrosine kinase)
d. cell-cell recognition
e. intercellular joining
f. attachment to the cytoskeleton and extracellular matrix (integrin)
4. The channels escort polar molecules, especially ions, across the non-polar interior
in the direction of lower concentration or favorable (unlike) net charge.
5. The pumps do the same, using ATP energy, when the gradient is unfavorable
(ATPase).
C. Membranes are self-assembling; they predate the origin of life. (Deamer, 1999)
1. Phospholipids self-assemble into bilayer envelopes in water.
2. So do fatty acids: the length of the fatty acid matters – and suggests that
phospholipids are of a set length that is ideal for bilayer stability
3. Meteorite contents reveal an array of soluble organic molecules: included in these
are fatty acids that self-organize into bilayer envelopes in water.
4. These envelopes are osmotically functional: they limit the flow of polar molecules
in and out.
II. Multicellularity
The overarching theme here is that cells living in colonies evidence cell specializations
and enzymes that are critical for the organisms that evolved from them.
A. Cyanobacteria are photosynthetic prokaryotes with a very long history in the fossil
record; evidence the stromatolites.
1. The earliest cyanobacteria are filaments of uniform cells.
2. However, with the advent of the oxygen-rich atmosphere, cyanobacteria evolved
specialized cells to cope with a problem: their nitrogen-fixing enzymes are permanently
rendered inactive by oxygen. These cells are oxygen-free nitrogen-reduction factories
called heterocysts. The rest of the cells in the colony do the photosynthesis.
B. Choanoflagellates
1. Choanoflagellates are colonial one-celled eukaryotes that secrete a communal stalk.
2. Current opinion is that they are ancestral to sponges and thus to metazoans.
3. The colonial cells have tyrosine kinase, a key signal receptor in the functioning of
metazoans.
4. Tyrosine kinase is a membrane-bround dimeric protein that functions in the binding of
small signal proteins and the transduction of this binding event into action inside the cell.
5. Inside the cell, tyrosine residues are phosphorylated, leads to the activation of proteins
that carry out cell functions. [The lin-3 gene we are studying in the C. elegans lab
constructs a small protein that interacts with a tyrosine kinase in the membrane of the
future vulva cells.]
C. Sponges
1. An introduction to sponges: filter feeders with flagellated cells (choanocytes) that
move water through porocytes into the large central cavity, in the process filtering food
from the water.
2. Sponges also have amoebocytes that can move about the animal, as well as other
specialized cells.
3. Sponges have recently been shown to have the integrin proteins that are critical to
integration of the metazoans, so sponge specialists argue that sponges are true metazoans.
4. Integrins are cell-membrane proteins that sense the extracellular environment and
signal to the cell to control differentiation, survival, and migration of cells.
5. The integrins are connected directly to fibronectin proteins, and indirectly through
these to the collagen and proteoglycan proteins. (Note, these are the three major kinds of
proteins in the extracellular matrix.)
6. The extracellular matrix is as important as the cell in understanding the animals as
organisms.
7. Sponges are known from the Late Proterozoic (Precambrian): the invention of integrins
and of cells integrated into true organisms happened long ago.
III. Distinguishing Self from Non-self: the Immune System
The approach in this section of the lecture is to address two difference human health
problems, allergies and AIDS, as examples of the function of the two fundamental
aspects of the immune system, the humoral and cell-mediated responses.
A. Allergies
1. Components of the blood and focus on the whie blood cell types:
Monocytes: phagocyte
Neutrophils: phagocyte
Basophils: histamine producers (dliation and increased permeability of capillaries)
Eosinophils: protection against large blood invaders like blood flukes
Lymphocytes ….
2. Focus on the lymphocytes, b (maturing in bone marrow) and t (maturing in the thymus)
3. Introduction to receptor proteins and their soluble counterparts, the antibodies. The
key point here is the specificity of the binding of the variable region of the
immunoglobulin with the epitope a specific peptide (or sometimes carbohydrate)
sequence of the antigen, called.
4. B-lymphocyte receptor proteins interact with antigens, yielding clones of antigenspecific memory B cells and plasma B cells.
5. The plasma B cells produce the antibodies, which are soluble receptors that bind to
these antigens (humoral means in solution, referring to these antibodies operating in
solution, indpendent of cells).
6. Thus memory (through setting aside some of the B cells as memory cells) and
specificity (through the precise match of antibody to antigen) are developed.
7. Allergies are the result of pollen-secific antibodies binding with mast cells, and pollen
binding to these bound antibodies (now receptors), leading to histamine release and
allergy symptoms.
B. HIV and AIDS 1 – the cell-mediated immune response
1. The interaction of cells via MHC proteins is central to the cell-mediated immune
response.
2. MHC-1 proteins, located on virtually all living animal cells, present peptides from the
cell interior, including antigens, for inspection by cytotoxic T cells.
3. MHC-2 proteins present the same fragments, but only from the interior of selected
white blood cells called antrigen-presenting cells, including T cells, macrophages, and
dendritic cells.
4. Receptors (similar to those on B cells) bind to the antigens; cytotox T cells kill the
infected cells presenting the antigens.
5. Helper T cells react to a bound antigen by cloning itself, yielding more helper T cells
and memory T cells with these receptors as well as cytotoxic T cells and plasma B cells
with the same specificity.
6. Cytokines are the small messenger proteins that T cells use to stimulate these cloning
events.
6. The first encounter with an antigen in the organism is up to dendritic cells, which are
macrophages specialized for working the body frontiers, hunting for invaders.
B. HIV and AIDS 2 – HIV’s attack on antigen-presenting cells
1. HIV is a retrovirus (lacks RNA, incorporates its RNA into the DNA of a host cell,
where its RNA is replicated).
2. HIV infection yields a typical immune response, with rapid increase in antibodies
specific to the virus as well as T cell concentration.
3. However, the continued attack on the antigen-presenting cells those with MHC-II
proteins (using the CD-4 link-stabilizing protein and cytokine receptors to gain entry to
the cell) eventually depletes the population of these cells, compromising the cellmediated immune system.
IV. Self and non-self involving Plants
Here, the theme is an exploration of various departures from the rejection of nonself cells by self cells as exemplified by the immune system. To keep things balanced,
we consider these departures mostly using plants, but end up with the origin of eukaryotic
cells – the most significant departure from rejecting non-self in the history of life.
A. Mycorrhizae
1. Mycorrhizae are symbiotic relationships between fungi and plant roots: there are two
types, ectomycorrhizae and endomycorrhizae.
2. Mycorrhizae are ancient (they are known from the most primitive land
plants),widespread (most mushrooms are producing spores for mycorrhisal fungi), and
specific (a mush room species usually has a specific host preference).
3. Mycorrhizae infect plant roots in the apoplast (which requires understanding the
difference between the apoplast and the symplast in the plant body.)
4. The symplast is the realm within the common membrane-bound cytoplasm of the plant,
interconnected through all cells by the plasmodesmata.
5. Mycorrhizal fungi, though they appear to enter into the interior or the cortex cells in
roots, in fact are always contained in the apoplast, though their hyphae (filaments)
penetrate and fill the inside of the apparent cell boundaries.
6. In contrast, a pathogenic fungus is immediately recognized as non-self by an immunelike interaction of receptor proteins with fungus antigens, yielding 1) cell-wall thickening
at the site of contact, 2) movement of the nucleus to the battle zone, and 3) in the event of
invasion, apoptosis (programmed cell death) of the cell.
B. Bacteria symbiotic with plants: Root Nodules and Stem Greenhouses
1. Root nodules resemble mycorrhizae in being symbiotic relationships, this time
between nitrogen-fixing bacteria and the roots of legume-family plants.
2. Interaction of the bacteria, originally in the soil, with the roots, leads to invasion of the
bacteria via root hairs and organization of a bacterial colony in a prominent nodule with
vascular tissue connecting to the vascular cylinder of the root.
3. Another nitrogen-fixing bacterium, this time a cyanobacterium, infects the stem cortex
of Gunnera, a tropical plant that lives in disturbed, nitrogen-poor habitats.
C. Parasitic Plants
1. Parasitic plants are common in the tropics – they provide no benefit to their host, but
they get both a physical niche and nutrition from their host.
2. Parasite seeds are stimulated to germinate by compounds in the host plant;
establishment of the haustorial (plant-plant) connection also requires sensing of host
compounds by the parasite.
3. The self-nonself response is not triggered in this interaction.
4. In one case, a parasitic plant has incorporated genes from the host through horizontal
transfer of genetic material from the mitochondria.
D. Origin of Eukaryotic Cell
1. Both mitochondria and chloroplasts are interpreted as engulfed but tolerated
prokaryotes living inside a host prokaryote.
2. The evidence: plastid membrane proteins are homologous to procaryote proteins, and
chromosome structure (one circle) and chemistry (no histones) are like prokaryotes
[plus several additional features]
3. Many plastid proteins are encoded in the nucleus, suggesting that there has been
horizontal transfer of genes from the plastids to the nucleus. Primitive plants and
animals have larger plastid genomes, suggesting the same history.
4. The advantage for the chloroplast ancestor may have been protection from the
oxidizing atmosphere – reminiscent of the logic for the evolution of heterocysts.
V. Development
A. totipotency:
1. The classic experiment was with carrots: isolated root cells could be cultured to
produce whole new plants.
2. Cell differentiation during development depends on selective expression of the whole
genome present in every cell.
3. Stem cells reveal the same insights: they can be nurtured to produce various
specialized cells depending on the environment provided to them.
B. blastula to gastrula: comparative analysis yields insights into the general nature of
development
1. general pattern: differential cell division at the vegetal pole leads to invagination of the
digestive tract: gastrulation ends with the primitive gut (archenteron) in place.
2. overall differences relate to the distribution of yolk (food resource) in the zygote and
hence the early embryo
3. three germ layers are evident at the end of gastrulation
a. ectoderm – the set of cells on the exterior of the animal
b. endoderm – the set of cells lining the archenteron
c. mesoderm – a third layer, lying in the interior between the other two
4. The germ layers have specific targets for their cell descendants in the mature organism.
C. the three fundamental processes:
1. They are:
–cell division (differential rates of division are critical, programmed cell death is
significant)
–cell differentiation (changes in integration and shape are critical; targeting cells with
signals is a critical part of the process)
–morphogenesis of tissues and organs (includes defining the individual’s polarities,
dividing the organism into segments, and – in animals -- migration of cells in tissue
origin)
2. The targeting of cell descendants governs cell differentation, best seen in C. elegans,
where the fate of every cell of the embryo is known.
3. For instance, signaling leads to dedication of one of four early embryo cells to yield all
the intestines from one of its daughters.
4. Similarly, the targeting of vulval precursor cells by anchors cells leads to formation of
the vulva – as seen in the lab on the lin-3 mutant.
5. Apoptosis ( programmed cell death) is significant in shaping the growing body of
worm or vertebrate. [not covered in detail this year]
6. Morphogenesis begins with definition of polarity in the egg by the mother – best
exemplified by work in Drosophila, the fruit fly.
7. Once polarity is established, a series of genes divide the embryo into segments.
D. Homeotic genes and the determination of appendage identity
1. The antennipedia mutant captures the whole idea of homeotic genes: a perfect leg is
programmed to develop, but too early in development, so it appears where an antenna
normal belongs.
2. Homeotic genes have a characteristic, highly conserved region of 180 nucleotides in
their DNA called a homeobox.
3. The homeobox codes for a homeodomain of 60 amino acids in the protein, which
assemble into three alpha helices.
4. These alpha helices are critical the gene function, which is interacting with DNA as a
transcription factor – that is they turn on other genes.
5. Homeotic genes come in families: members of the families determine events on
different segments – the members are called paralogs (that is they are paralogous with
one another).
6. The copies of the genes that control functions in equivalent segments can be compared
between species – these are orthologs (that is they are orthologous with one another.)
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Begin with totipotency and the dependent conclusion that development depends on
selective expression of the whole genome present in every cell.
Then begin comparison of developmental events with gastrulation, then early
organogenesis in the frog.
Review these events to outline the three fundamental processes:
a. cell division (differential rates of division are critical, programmed cell death is
significant – notably in digit differentiation see p 429)
b. cell differentiation (changes in integration and shape are critical; targeting cells
with signals goes here as a mechanism)
c. morphogenesis of tissues and organs (includes individual’s polarities,
segmentation, and cell migration in animals)
Cell changes
Shape
Integration
Position
Tissue change
Folding (neural crest)
Cavity origin=split (coelom)
Condensation
Then address the evolution of development and the dependent adult features.
OLD OUTLINE
Totipotency and stem cells
Animals: morphogenesis of the three germ layers--blastula and gastrula
Organogenesis: folds, splits, and condensations in germ layers
Cell processes: changes in shape, position, adhesion
Plants: permanently embryonic, modular, no cell migration
ORIGINAL TOPIC LIST
1) phospholipid bilayers: membrane proteins and messengers
11
2) multicellularity: origin in colonies with specialization: Nostoc and toxic oxygen
26: 512-526
27:538-540;
3) multicellularity (establishing self-self boundaries) leads to development with
differentiation: cell lineages and cell-to-cell messengers in elegans
21
4) multicellarity (i.e. self-self boundaries) leads to development with
differentiation: introducing organismal polarity
21
5) multicellarity (i.e. self-self boundaries) leads to development with
differentiation: segmentation (hence HBOX) and thus --21
6) evo-devo: consequently paralogy and orthology..
21: 431-432
7) evo-devo: molecular homology leads to a consideration of organismal
homology and variations on the theme of locomotion, beginning with
crab and lobster
33:656-665(arthropods)
449:1063-1074 (locomotion)
8) self-environment: plants — boundaries with the environment: stomates and root
hairs [OR SOMETHING EVOLUTIONARY]
36
9) self-environment: boundaries with the environment: alveolae (respiration with
swim bladder-lung history), small intestine (food absorption), including
vegetarian animal variations: foregut, hindgut, dinosaur
41 (animal nutrition)
10) self-environment: sensory systems intro(phylogeny and action potential)
32: invertebrate diversity
49: sensory systems
11) self-environment: sensory systems: synapse and ecology of plant toxins
32
12) self-environment: sensory systems: odor and navigation
32
13) spare lecture self-nonself: the first frontier showdown - origin of eukaryotes as
an invasion with détente
26: 523-525 (repeat of above)
14) self-nonself: root nodules and mycorrhizae as a more modern détente of the
same sort
37: 764-767
15) self-nonself: the immune system 43
16) self-nonself: the immune system
43
17) self-nonself boundaries: reproductive biology (sperm)
???
18) self-nonself boundaries: reproductive biology (pollen)
????
19) SPARE LECTURE
Relevant chapters in Campbell ed. 7
7 membrane structure and function
11 cell communication
21 evo devo
38 plant reproduction
39 plant signals
41 animal nutrition
42 circulation and gas exchange
43 immune system
45 animal reproduction
46 animal reproduction
47 animal development
48 nervous systems
49 sensory and motor mechanisms