Re: Human external and internal ecology

g:

>>From what I've found on the net "endosymbiosis" is widely accepted by
the scientific community. The one scientist most responsible or
targeted as such is microbiologist Lynn Margulis. Remember nothing in
science is a "fact" but if it stands up against other explanations and
there is evidence for it then it is a theory. You will find several
examples of scientific evidence here. Your mentioning the possibility
of mitochondria being a parasite is so incomplete I merely wanted to
point out what the majority of the scientific community thinks
regarding mitochondria. As one author states, "The SET states that the
evolution of eukaryotes from prokaryotes involved the symbiotic union
of several previously independent ancestors. According to the theory,
these ancestors included a host cell, an ancestor of mitochondria, an
ancestor of chloroplasts, and, more controversially, a prokaryote that
brought with it the structures that today provide cellular motion." It
is also apparently accepted by most scientists in this field. As
mentioned, although some of Margulis ideas remain controversial, there
is mounting evidence in support of the SET (Fausto-Sterling 1993). Some
of Margulis ideas are very controversial but the Serial Endosymbiosis
Theory doesn't appear to be one of them. Is there room for learning
more? Of course.

You wrote, "Also -- and this might strain the notion of beehive a bit,
since many of the little rascals running around in and on the human
body and ESSENTIAL to its health and survival are NOT "self" (i.e. do
not have the same RNA or DNA as the human host, but are just as (or
almost so) as *necessary to the health and the process of living of the
human host as those things in the external ecology, such as air, water,
food. To apparently prove your example of the "little rascals" of the
human body which are ESSENTIAL to its health and survival and don't
have the same RNA or DNA as the human host you sadistically and
sarcastically opine, "If one has perfectly healthy ears, except for
unsightly wax buildup that is visible to others, one can clean that wax
out with an antiseptic (especially a harsh one like rubbing alcohol)
and -- thus having disrupted the healthy
ecology of his outer and middle ear areas -- can soon find himself with
a hell of a bacterial or fungal ear infection. By the same token,
taking an oral antibiotic preparation can disrupt the ecology of the
digestive system and, here again, end up with a severe case of the
trots... or even the sprinters." Needless to say these bacteria and
viruses of the human body are not always essential to its health and
survival. However, there can be ways to minimize such "infections". For
example, only a very dysfunctional person would have a clump of dark
orange protruding from their ear(s). In many cases one would expect
another person to take care of their hygiene. I don't use rubbing
alcohol to clean my ears. Do you? I use cautiously Q-Tips or Debrox. As
far as taking oral antibiotics and getting the shits what the oral
antibiotics are fighting might be more severe for your health, yes? My
suggestion would be to control your diet, take Pepto Bismal, etc. If
all else fails (and especially if your elderly and something of an
invalid) Huggies should help. I don't consider your preface, "Also --
and this might strain the notion of beehive a bit, since many of the
little rascals running around in and on the human body and ESSENTIAL to
its health and survival are NOT "self" (i.e. do not have the same RNA
or DNA as the human host, but are just as (or almost so) as *necessary
to the health and the process of living of the human host as those
things in the external ecology, such as air, water, food" followed by
the mention of an ear infection and the shits from oral antibiotics
"coincidental".

g:
Will not go into advanced level in this introductory message, but wish
to point out simply this: That no study of human evolution (nor
biological evolution in general) is hitting on all its cylinders
without taking into consideration the little
fellow travelers that are and *indispensable part and parcel* of the
*system* that is the *human life process.*

Ragland:
Are we talking about mitochondria or pathological microorganisms?

g:
So, what say we give the little blighters a BIG HAND ! (Applause...
standing ovation...dying down gradually...)

Ragland:
The word "blighters" suggests pathological microorganisms. What do you
want to focus on? Mitochondria or pathological microorganisms? Despite
what you may think and feel, the two are not the same. Why would I give
a "big hand" to pathological microorganisms?

g:
Now, don't we feel better?

Ragland:
Only if you're a hater of yourself and human beings.

g:
Yes, sir. If we were deprived of certain ear-dwelling, gut-dwelling,
skin-dwelling, mouth and throat-dwelling, bladder-dwelling
microorganisms we
would not be able to hang around very long.

Ragland:
That is true. They provide a natural defense.

g:
An interesting question for discussion -- within this broader context
-- is
whether our batteries are "self" or hitchhikers. (Batteries? You
know...
mitochondria).

Ragland:
I think at various evolutionary stages they have been both.

g:
But then what is "self" itself? If we go far enough back in theory of
how
bio-evo changed until it got to where we are now (which is only an
interstitial stage between our earliest 'living' predecessor and what
our
progeny will be like another few hundred million years after today), we
get
back a time (in best known theories, at least) at which mitochondria
appear
to have been separate from whatever was to become us 'uns.

Ragland:
Well as much as a surprise as this may be at one time multicellular
organisms didn't exist. Before that unicellular organisms did. The term
"self" is an everchanging concept, not only in the abstract but
ultimately in the practical.

g:
Whether our ancestors ate mitochondria and the boogers would not die
(as
some of the bacteria in our gut do, today)... or whether the
mitochondria
infected our ancestors and were parasitic... such questions may never
be
conclusively answered.

Ragland:
I think the function of mitochondria is much more important than
shitting out live bacteria. I think it is misleading to state
mitochondria infected our ancestors and was parasitic as ultimately it
was advantageous to multicellular life.





Here is some information on Mitochondrion:


Prokaryotes gave rise to the first eukaryotic cells in a process known
as endosymbiosis. Symbiosis is an association between two or more
species, and endosymbiosis implies that one species was living inside
the other one, the host. The prokaryotes that gave rise to all
eukaryotes were probably from the domain Archaea because both
noticeable characteristics and DNA comparison suggest that these
monerans are more closely related to the eukaryotes.


The first step in developing eukaryotic cells, which did not involve
symbiosis, was membrane infolding. The plasma membrane folded inwards
to form a nuclear envelope around the nucleus, and may have also formed

the endoplasmic reticulum, attached to the nuclear envelope. Parts of
the endoplasmic reticulum may have branched to form the golgi apparatus

and other organelles of the endomembrane system.


However, the process of forming an eukaryotic cell was not complete.
All eukaryotes contain mitochondrion to convert potential energy to
chemical energy, and many contain chloroplasts that convert energy from

the sun to energy-rich sugar molecules that can be converted to
chemical energy in the form of adenosine triphosphate (ATP) by
chloroplasts.


Chloroplasts and mitochondrion evolved through a form of endosymbiosis.

According to one theory that is widely supported, mitochodrion evolved
from small heterotrophic prokaryotes that were engulfed by a larger
eukaryotic cells (where membrane infolding had occurred). The smaller
cell used cellular respiration to intake oxygen and convert organic
molecules to energy. These prokaryotic cells were too small to be
digestible, but continued to live inside the host cell. The prokaryotic

cells may have become dependent on the host cell for organic molecules
and inorganic compounds, and the host cell would have had an increased
output of ATP for cellular activities, and therefore would have been
more productive and more successful. Therefore, as the theory of
natural selection implies, these cells would have been more productive
because of the endosymbiotic relationship that they held, and could
have multiplied more, producing all eukaryotic cells, and eventually
leading to all eukaryotes.


Chloroplasts probably evolved in a manner similar to that of
mitochondrion. However, chloroplasts probably were ingested by only
some eukaryotic cells, and were ingested after the first mitochondrion.

This is why almost all eukaryotes have mitochondrion but only some have

chloroplasts. Certain eukaryotic cells ingested smaller prokaryotic
autotrophic cells. These cells were able to produce organic food
molecules for their host cells by fixing carbon, and the host cells
gave these prokaryotes inorganic compounds like CO2. Eventually, the
mitochondrion and chloroplasts became so interdependent that they
became organelles of the host cell.


There are many scientific discoveries that support the endosymbiotic
theory of evolution. For instance, mitochodrion and chloroplasts both
contain DNA, RNA, and ribosomes, all of which are similar to those of
prokaryotes. Also, mitochodrion and chloroplasts each have two
membranes, the outer one probably is a product of membrane infolding by

the host cell, but the inner one is probably the ancestral prokaryotes
plasma membrane. This is supported by the fact that enzymes and other
proteins in the inner membrane resemble their counterparts in
prokaryotes. Other similarities between these organelles and
prokaryotes include division by binary fission and DNA replication,
transcription and translation.






Evidence for endosymbiosis

Biologist Lynn Margulis first made the case for endosymbiosis in the
1960s, but for many years other biologists were skeptical. Although
Jeon watched his amoebae become infected with the x-bacteria and then
evolve to depend upon them, no one was around over a billion years ago
to observe the events of endosymbiosis. Why should we think that a
mitochondrion used to be a free-living organism in its own right? It
turns out that many lines of evidence support this idea. Most important
are the many striking similarities between prokaryotes (like bacteria)
and mitochondria:


Membranes - Mitochondria have their own cell membranes, just like a
prokaryotic cell does.

DNA - Each mitochondrion has its own circular DNA genome, like a
bacteria's genome, but much smaller. This DNA is passed from a
mitochondrion to its offspring and is separate from the "host" cell's
genome in the nucleus.


Reproduction - Mitochondria multiply by pinching in half - the same
process used by bacteria. Every new mitochondrion must be produced from
a parent mitochondrion in this way; if a cell's mitochondria are
removed, it can't build new ones from scratch.


When you look at it this way, mitochondria really resemble tiny
bacteria making their livings inside eukaryotic cells! Based on decades
of accumulated evidence, the scientific community supports Margulis's
ideas: endosymbiosis is the best explanation for the evolution of the
eukaryotic cell.

What's more, the evidence for endosymbiosis applies not only to
mitochondria, but to other cellular organelles as well. Chloroplasts
are like tiny green factories within plant cells that help convert
energy from sunlight into sugars, and they have many similarities to
mitochondria. The evidence suggests that these chloroplast organelles
were also once free-living bacteria.

The endosymbiotic event that generated mitochondria must have happened
early in the history of eukaryotes, because all eukaryotes have them.
Then, later, a similar event brought chloroplasts into some eukaryotic
cells, creating the lineage that led to plants.



Despite their many similarities, mitochondria (and chloroplasts) aren't
free-living bacteria anymore. The first eukaryotic cell evolved more
than a billion years ago. Since then, these organelles have become
completely dependent on their host cells. For example, many of the key
proteins needed by the mitochondrion are imported from the rest of the
cell. Sometime during their long-standing relationship, the genes that
code for these proteins were transferred from the mitochondrion to its
host's genome. Scientists consider this mixing of genomes to be the
irreversible step at which the two independent organisms become a
single individual.

The Serial Endosymbiosis Theory of Eukaryotic Evolution
by
Jeremy Mohn

(c) 1998


--------------------------------------------------------------------------------

The transition between eukaryotes, cells with nuclei, and prokaryotes,
cells which lack nuclei, is considered by many biologists to be the
most profound change in evolutionary history. In an attempt to describe
the way in which this gap was bridged, scientists have proposed the
serial endosymbiosis theory (SET). The term "endosymbiosis" specifies
the relationship between organisms which live one within another
(symbiont within host) in a mutually beneficial relationship. The SET
states that the evolution of eukaryotes from prokaryotes involved the
symbiotic union of several previously independent ancestors. According
to the theory, these ancestors included a host cell, an ancestor of
mitochondria, an ancestor of chloroplasts, and, more controversially, a
prokaryote that brought with it the structures that today provide
cellular motion.

The idea that the eukaryotic cell is actually a colony of microbes was
first suggested in the 1920s by American biologist Ivan Wallin
(Fausto-Sterling 1993). The originator of the modern version of the SET
is biologist Lynn Margulis. In 1981, Margulis published the first
edition of her book entitled Symbiosis in Cell Evolution in which she
proposed that eukaryotic cells originated as communities of interacting
entities that joined together in a specific order. With time, the
members of this union became the organelles of a single host (Margulis
1993). The organelle progenitors could have gained entry into a host
cell as undigested prey or as an internal parasite after which the
combination became mutually beneficial to both organisms. As the
organisms became more interdependent, an obligatory symbiosis evolved.

The SET postulates that the ancestors of mitochondria were free-living
bacteria, similar to today's Daptobacter and Bdellovibrio, that
developed the ability to efficiently respire oxygen (Margulis and Sagan
1987). The ancestors of chloroplasts, today's cyanobacteria, were
originally independent photosynthetic organisms. In addition, the
whiplike cilia that are common in eukaryotes but are not found in
prokaryotes are thought to have derived from still another group of
free-living bacteria, the modern spirochetes. According to the SET, the
original prokaryotic host cell was an archaebacterium, similar to
today's Thermoplasma, that could withstand high temperatures and
acidic conditions (Margulis and Sagan 1987). This host cell was neither
photosynthetic nor capable of effectively using oxygen.

Throughout her writings, Margulis contends that symbiosis is a major
driving force behind evolution. In her opinion, cooperation,
interaction, and mutual dependence among life forms allowed for
life's eventual global dominance. As a result, Darwin's notion of
evolution as the "survival of the fittest," a continual competition
among individuals and species, is incomplete. According to Margulis and
Sagan (1986), "Life did not take over the globe by combat, but by
networking." Rather than focus solely on the elimination of
competitors, Margulis' view of evolution downplays competition itself
on the basis of symbiotic relationships.

One early and important discovery in support of the SET occurred in the
laboratory of Kwang W. Jeon, a biologist at the University of
Tennessee. Jeon witnessed the establishment of an amoeba-bacteria
symbiosis in which new bacterial symbionts became integrated in the
host amoeba (Jeon 1991). In 1966, when the bacteria first infected the
amoebas, they were lethal to their hosts. However, as time progressed,
some of the infected amoebas survived and became dependent on their
newly acquired endosymbionts within a few years. Jeon was able to prove
this dependency by performing nuclei transplants between infected
amoebas and amoebas lacking the bacteria. If left alone, the hybrid
amoebas died in a matter of days. Yet if he reinfected these hybrids
with the once-lethal bacteria, the amoebas recovered and once again
began to grow (Margulis and Sagan 1987). This discovery served to
demonstrate that endosymbiosis could provide a major mechanism for
cellular evolution and explain the introduction of new species (Jeon
1991).

Although some of Margulis' ideas remain controversial, there is
mounting evidence in support of the SET (Fausto-Sterling 1993). The
bulk of this evidence serves to defend the notion of an endosymbiotic
origin of mitochondria and chloroplasts. The recognition that new
mitochondria and chloroplasts can arise only from preexisting
mitochondria and chloroplasts was one of the first clues. Scientists
found that mitochondria and chloroplasts cannot be formed in a cell
that lacks them because nuclear genes only code for some of the
proteins of which they are made. Also, both mitochondria and
chloroplasts have their own sets of genes that are more similar to
those of prokaryotes than those of eukaryotes. They both contain a
circular molecule of DNA, just like that found in prokaryotes. Finally,
both mitochondria and chloroplasts have their own protein-synthesizing
machinery. Their ribosomal structures and their ribosomal RNA (rRNA)
more closely resemble those of prokaryotes. These three lines of
evidence have been cited to firmly establish the theory of the origin
of mitochondria and chloroplasts through the process of endosymbiosis.

The least accepted and most questionable aspect of the SET is the
hypothesis that eukaryotic undulipodia originated from spirochete
bacteria (Margulis 1993). The term "undulipodia" is used to describe
the eukaryotic motility organelles, flagella and cilia. Undulipodia are
composed of microtubules in a specific configuration. Microtubules are
comprised of several closely related proteins called tubulins. These
structures are far larger and more complex than bacterial flagella,
which are made of flagellin proteins. The SET postulates that
undulipodia may be derived from bacteria through motility symbioses
(Bermudes, Margulis, and Tzertzinis 1987). This idea is referred to as
the exogenous hypothesis. The details of the argument are complex, but
the supporters of the SET point to several lines of circumstantial
evidence. Their argument emphasizes the biology of the organelles
themselves, their distribution, and the occurrence of related and
analogous structures. Opponents of this view, supporters of the
endogenous hypothesis, suggest that undulipodia originated internally
as an extension of the microtubules utilized in mitosis. This
hypothesis is also referred to as direct filiation, which is the
nonsymbiotic view of evolution that emphasizes the role of various
kinds of mutations in the evolutionary separation of eukaryotic cells
from prokaryotic cells.

The main controversy between the endogenous and exogenous hypotheses
for the origin of undulipodia rests upon a question of chronology.
Proponents of the endogenous hypothesis claim that microtubules
preceded the origin of undulipodia, which eventually arose
endogenously. In contrast, the exogenous hypothesis states that
motility symbioses gave rise to cells with undulipodia, and this
acquisition subsequently led to the internal structures involved in
mitosis (Bermudes, Margulis, and Tzertzinis1987). Although the
symbiotic origin of undulipodia is gaining support, the controversy is
yet to be solved. According to Bermudes and Margulis (1985), there is
insufficient evidence to prove either direct filiation or the symbiotic
hypothesis for the origin of undulipodia.

An important distinctive element of the SET is the overall chronology
of symbiotic acquisitions in the origin of the eukaryotic cell. In
order to fully understand the theory's implications for the
classification of all life forms, a brief summary of the current
interpretation of endosymbiotic events is necessary. According to the
theory, eukaryotes evolved when archaeal and eubacterial cells merged
in anaerobic symbiosis. The archaeal cell provided the cytoplasm while
the eubacterial cell (a spirochete) allowed for mobility and,
eventually, mitosis. Some of these anaerobic cells then incorporated
oxygen-respiring eubacteria (similar to Daptobacter or Bdellovibrio) to
become mitochondria-containing aerobes from which most protoctists,
animals, and fungi evolved. Finally, some of these aerobes went on to
incorporate photosynthesizing cyanobacteria to become
chloroplast-containing algae and plants. The divisions or domains
implied by this description (Archaea, (true)Bacteria, and Eukarya) are
consistent with the widely acknowledged classification system described
by Olsen, Woese, and Overbeek (1994).

Although the nucleus is the defining characteristic of the eukaryotic
cell, the origin of this organelle and its relation to symbiosis is
uncertain. Margulis tends to favor a process involving the combination
of direct filiation and symbiosis as the source of the nucleated cell.
She believes that some prokaryotic cells evolved primitive nuclei
through direct filiation but remained prokaryotic. Others evolved these
same structures but also acquired other symbiotic genes and
consequently became eukaryotes (Margulis 1993). Overall, the
traditional view of the origin of the nucleus states that the nuclear
genome originated through direct evolution from an archaebacterial
ancestor.

A 1996 paper by Golding and Gupta disputes the traditional view of the
origin of the nucleus and suggests an alternative called the chimeric
model. The term "chimeric" refers to an organism containing tissues
from at least two genetically distinct parents. The chimeric model
proposes that the first eukaryotic cell arose as the result of a
unusual fusion event between a Gram-negative eubacterium (host) without
a cell wall and an archaebacterium (symbiont) in which both parents
made major contributions to the cell's nuclear genome. The nucleus
appeared as the result of the folding in of the host's membrane
around the engulfed cell. Such fusion events are generally rejected by
supporters of the SET because of the inability of present-day bacteria
to envelope prey.

The chimeric model is based on genetic and biochemical evidence. One
piece of genetic evidence that supports the model is the fact that
prokaryotic cells are homogenomic (having genetic material from one
parent only), whereas eukaryotic cells are heterogenomic (having
genetic material from more than one parent). Biochemical evidence in
support of the chimeric model involved the phylogenetic, or
evolutionary, analysis of sequence data from proteins. This analysis
demonstrated a close relationship between Gram-negative bacteria and
eukaryotes on one hand and Gram-positive bacteria and archaebacteria on
the other (Golding and Gupta 1996). Even more protein sequence data
suggested a relationship between eukaryotes and archaebacteria. These
data imply that a symbiotic relationship between Gram-negative bacteria
and archaebacteria as the progenitors of the eukaryotic cell is
feasible. Overall, the sequence data support the chimeric model.

Recent research by Martin and Müller (1998) into the origin of the
mitochondrion has led to a new theory of endosymbiosis called the
"hydrogen hypothesis." In the current picture of the origin of the
eukaryotic cell, the mitochondrion was a "lucky accident" (Vogel 1998).
The ancestral host cell simply engulfed the mitochondrion ancestor, did
not fully ingest it, and an even more successful cell resulted.
According to the hydrogen hypothesis, however, the first eukaryotic
cell did not form simply by accident. Instead, it was the result of a
purposeful union between an archaebacterial host cell, a methanogen
that consumed hydrogen and carbon dioxide to produce methane, and a
future mitochondrion symbiont that made hydrogen and carbon dioxide as
waste products of anaerobic metabolism. Thus, although the symbiont was
probably capable of aerobic respiration, the symbiosis began as a
result of the products of anaerobic metabolism. The host's dependence
upon hydrogen produced by the symbiont is identified as the selective
principle that consolidated the common ancestor of eukaryotic cells
(Martin and Müller 1998).

The hydrogen hypothesis has some important implications that contradict
the current view of the relationship between eukaryotes and
archaebacteria. In the current view, the eukaryotes branched off from
the archaebacteria long before the archaebacteria had divided into
their present-day groups. The hydrogen hypothesis implies that the
first eukaryotes appeared much later in the evolutionary picture,
meaning they are more closely tied to the archaebacteria. In order for
the hydrogen hypothesis to be confirmed, an analysis of the complete
sequences of eukaryotic and archaebacterial genomes must be completed
(Vogel 1998).

Another recent explanation of the origin of eukaryotes called the
"syntrophic hypothesis" was presented by López-García and Moreira
(1998). Though they were independently proposed, the syntrophic
hypothesis is complementary in several aspects to the hydrogen
hypothesis. Both hypotheses agree in the suggestion of an anaerobic
metabolism for the origin of mitochondrial symbiosis. They are also
strikingly similar in some metabolic details of the symbiosis and
archaeal molecular features (López-Garcia and Moreira 1998). The major
difference between the two hypotheses is in the nature of the original
bacterial partnership. As previously stated, in the hydrogen
hypothesis, the original symbiosis is thought to have taken place
between a methanogenic archaebacterium and a eubacterial ancestor to
the mitochondrion. In the syntrophic hypothesis, the original symbiosis
is conceived to have taken place between a methanogenic archaebacterium
and an ancestral sulfate-respiring delta-proteobacterium. The former
provided the central genetic material and nucleic acid metabolism while
the latter provided most metabolic characteristics (López-Garcia and
Moreira 1998). Mitochondria are thought to have derived from a later,
independent symbiotic event. As with the hydrogen hypothesis, further
genetic sequencing analyses are necessary in order for the claims of
the syntrophic hypothesis to be upheld.

It has been nearly thirty years since Lynn Margulis first published a
book on the origin of eukaryotic cells. Since that time, biology has
undergone extraordinary changes. The most noticeable change is the
extensive accumulation of sequence data for both nucleic acids and
proteins. The collection of new data will undoubtedly lead to
continuous revision of the serial endosymbiosis theory of the origin of
the eukaryotic cell. Despite the uncertain future, the crucial
foundation has been laid. Symbiosis is now accepted by the scientific
community as an important factor in generating evolutionary change. The
next steps include the development of more elaborate methods to
interpret genetic and molecular sequence data and the undertaking of a
fresh look at the fossil record. These tactics might reveal significant
information concerning one of the most challenging and fascinating
problems in evolutionary biology, the origin of the eukaryotes.


--------------------------------------------------------------------------------

Bibliography
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of Undulipodia. In: Endocytobiology III (eds. John J. Lee and Jerome F.
Fredrick). The New York Academy of Sciences, New York, pp. 187-197.

Bermudes, D., and L. Margulis. 1985. Symbiosis as a Mechanism of
Evolution: Status of the Symbiosis Theory. Symbiosis 1: 101-124.

Fausto-Sterling, A. 1993. Is Nature Really Red in Tooth and Claw?
Discover 14: 24-27.
Jeon, K.W. 1991. Amoeba and x-Bacteria: Symbiont Acquisition and
Possible Species Change. In: Symbiosis as a Source of Evolutionary
Innovation (eds. L. Margulis and R. Fester). The MIT Press, Cambridge,
Mass., pp. 118-131.

López-García, P., and D. Moreira. 1998. Symbiosis Between
Methanogenic Archaea and delta-Proteobacteria as the Origin of
Eukaryotes: The Syntrophic Hypothesis. Journal of Molecular Evolution
47: 517-530.

Margulis, L. 1981. Symbiosis in Cell Evolution, 1st Edition. Freeman,
New York.

Margulis, L. 1993. Symbiosis in Cell Evolution, 2nd Edition. Freeman,
New York.

Margulis, L., and D. Sagan. 1986. Microcosmos. Summit Books, New York.

Margulis, L., and D. Sagan. 1987. Bacterial Bedfellows. Natural History
96(3): 26-33.

Martin, W., and M. Müller. 1998. The Hydrogen Hypothesis for the First
Eukaryote. Nature 392: 37-41.

Olsen, G.J., C.R. Woese, and R. Overbeek. 1994. The Winds of
(Evolutionary) Change: Breathing Life into Microbiology. Journal of
Bacteriology 176(1): 1-6.

Vogel, G. Did the First Complex Cell Eat Hydrogen? Science 279:
1633-1634.



Both the structure and the function of mitochondria were mysteries
in 1920. The internal anatomy of bacteria was also almost totally
unknown. The evidence Wallin needed to support his theory required the
electron microscope and other sophisticated laboratory techniques
developed only after World War II. As in the case of continental drift,
the theory of symbiosis in cellular evolution that was finally accepted
during the 1970s was very different from the one suggested by Wallin in
the 1920s.

LYNN MARGULIS: A REVOLUTlONARY SClENTlST

Like the eventual acceptance of continental drift, acceptance of a
symbiotic theory of cell evolution has often been hailed as a
scientific revolution The woman most responsible for bringing the idea
to scientific respectability is Lynn Margulis. A prolific writer and
dynamic speaker, Margulis captivates audiences and often irritates more
traditional biologists with her unorthodox ideas. A profile in Science
described her as an unruly provocateur, but as one of the world's
leading authorities on cellular evolution, she supports her claims with
abundant evidence. Although many biologists continue to disagree with
some of her ideas, everyone takes endosymbiosis seriously.

Margulis entered biology during a particularly exciting period.
James Watson and Francis Crick were just discovering the structure of
DNA when Margulis was in college. A few years later, when she was a
graduate student, two of her professors discovered DNA in chloroplasts.
Other scientists reported finding DNA in mitochondria. Because these
early reports were hotly disputed, searching for DNA outside the
nucleus was not the sort of research project that most graduate
students would have chosen. Despite warnings, Margulis plunged into the
controversial problem for her Ph.D. dissertation. Using radioactively
labeled nucleotides, she convincingly demonstrated the presence of DNA
in the chloroplasts of Euglena gracilis, one of the curious unicellular
organisms that shares both plant and animal characteristics.

Margulis wrote her first article on the endosymbiotic theory in
1967, two years after she completed her Ph.D. At the time, she was a
single mother without a permanent teaching position. She was also
writing her first book on endosymbiosis, which sparked a lively
controversy when it was published in 1970. Although it initially
brought Margulis notoriety, the controversy over cellular evolution was
rather short lived. By the time she published a second book on
endosymbiosis in 1981, most biologists accepted important parts of her
theory. As a result, Margulis became a scientific celebrity whose
success was publicized in both popular and professional magazines.

BACKGROUND TO A CONTROVERSY

In 1970, when Margulis's first book was published, most biologists had
never heard of endosymbiosis. Those who knew about it usually dismissed
it. In order to succeed, Margulis had to carefully distinguish her
ideas from the discredited theory proposed by Ivan Wallin half a
century earlier. She also had to overcome a basic assumption about
evolution held by nearly all biologists at the time. According to the
traditional view, evolution usually occurs gradually; endosymbiosis,
however, is based on the idea of rather sudden evolutionary changes.
Finally, Margulis had to convince biologists to take DNA in the
cytoplasm seriously. Although evidence for DNA in chloroplasts and
mitochondria was growing stronger, the idea that some genes reside
outside the nucleus remained unorthodox.

Despite these biases against endosymbiosis, Margulis's book was
widely read. Even those who strongly disagreed with her did not
ridicule her theory the way biologists had belittled Ivan Wallin's
theory about the evolution of mitochondria. Indeed, the book convinced
many biologists that cellular evolution was an exciting, if
controversial, field. How had cell biology changed during the 50 years
after Wallin proposed his unsuccessful theory?

Much more was known about the internal structure of cells in 1970
than in 1920. Unlike Wallin, who knew little about the internal
structure or function of mitochondria, Margulis had access to a great
deal of information about the intemal structure of cells when she wrote
her book. Powerful electron microscopes, perfected after World War II,
allowed scientists to study the previously hidden parts of organelles.
Using new biochemical techniques, scientists were able to discover many
details of cellular activities. Mitochondria, long an enigma, were now
known to be important sites of adenosine triphosphate (ATP) production,
and for the first time scientists were beginning to under stand how
this critical process occurred on mitochondrial membranes. By 1970
biologists also became aware of major differences between prokaryotic
bacteria, which lack nuclei and most other organelles, and eukaryotic
cells, which have both. The sharp discontinuity between prokaryotes and
eukaryotes, which previously had not been fully recognized, was
highlighted by Robert Whittaker's new system of classification, which
used the two cell types to distinguish kingdom Monera from four
eukaryotic kingdoms (Animalia, Plantae, Fungi, and Protista). The
prokaryotic/eukaryotic distinction was now at the forefront of
biological attention. What other similarities and differences might be
found between the two types of cells? How had eukaryotic cells evolved?
What was the evolutionary significance of the DNA found in some
organelles? These were the questions that Margulis set out to answer in
1970.






click to see larger version

THE SERlAL ENDOSYMBlOTlC THEORY (SET)

According to Margulis, eukaryotic cells evolved through a series of
symbiotic partnerships involving several different kinds of prokaryotic
cells. The smaller partners invaded larger host cells and eventually
evolved into three different kinds of organelles: mitochondria,
chloroplasts, and flagella. Because these evolutionary steps supposedly
occurred as a series of discrete events, Margulis's theory is often
referred to as the SET: serial endosymbiotic theory.

Like other evolutionary biologists, Margulis believes that life
first appeared on the earth about four billion years ago. The first
organisms were extremely simple--microscopic droplets of water
containing a few genes and enzymes surrounded by a membrane. They fed
on abundant organic molecules that had been produced earlier in the
earth's history by various nonliving chemical processes. Like some
modern bacteria, early prokaryotic cells extracted energy from these
molecules by fermentation, using various forms of metabolism that do
not require oxygen.

Luckily for the fermenters, there was almost no oxygen in the
atmosphere. If there had been, the primitive cells would have been
poisoned by this highly reactive gas. Later, as the supply of
energy-rich molecules in the watery environment began to be depleted,
other types of bacteria evolved which used solar energy to synthesize
their own supplies of large, organic molecules. These early
photosynthetic bacteria were also anaerobic. In other words, they did
not use oxygen and their primitive photosynthetic reactions did not
produce oxygen as a by-product. For over a billion years, primitive
ecosystems included only two types of prokaryotic organisms: simple
photosynthetic bacteria and fermenting bacteria.

Perhaps 2.5 billion years ago, a new group of photosynthetic
bacteria evolved, the ancestors of today's cyanobacteria. These
advanced photosynthesizers split water to produce the hydrogen ions
(H+) needed to build sugar molecules. A byproduct of this
water-splitting reaction was oxygen gas. This was a catastrophic event
in the history of life. Oxygen is such a reactive element that it
easily destroys delicate biological structures. As the amount of oxygen
in the atmosphere increased, most species of anaerobic bacteria were
driven to extinction, victims of the earth's first case of air
pollution. Some survivors retreated to areas of brackish water or other
oxygen-depleted habitats, where their anaerobic descendants still
flourish today. A few prokaryotes became aerobic by evolving various
mechanisms to detoxify oxygen. The most successful of these processes
was respiration, which not only converted toxic oxygen back into
harmless water molecules, but also generated large quantities of ATP.

According to the SET, the photosynthetic production of oxygen gas
and the subsequent evolution of respiration set the stage for the
evolution of all eukaryotic cells. This evolutionary process occurred
in several separate symbiotic events. The first eukaryotic organelles
to evolve were mitochondria--structures found in almost all eukaryotic
cells. In Margulis's theory, small respiring bacteria parasitized
larger, anaerobic prokaryotes. Like some bacteria today (Bdellovibrio),
these early parasites burrowed through the cell walls of their prey and
invaded their cytoplasm. Either the host or the parasite was often
killed in the process, but in a few cases the two cells established an
uneasy coexistence. The mutual benefits to the partners are obvious.
The respiring parasite, which actually required oxygen, would allow its
host to survive in previously uninhabitable, oxygen-rich environments.
Perhaps the parasite also shared with its host some of the ATP that it
produced using oxygen. In exchange, the host provided sugar or other
organic molecules to serve as fuel for aerobic respiration. Eventually,
as often occurs with parasites, the protomitochondria lost many
metabolic functions provided by the host cell. Similarly, as oxygen in
the atmosphere continued to increase, the host became more and more
dependent upon its pro-tomitochondria to detoxify the gas. What began
as a case of opportunistic parasitism evolved into an obligatory
partnership. The small respiratory bacteria eventually evolved into the
mitochondria of eukaryotic cells.

Although virtually all eukaryotic cells contain mitochondria, only
those of plants and certain protists contain chloroplasts. Therefore,
it seems likely that chloroplasts evolved in only a few lines of
eukaryotic cells, and this event occurred after mitochondria were
already well established. How did this new evolutionary partnership
evolve? With higher metabolic rates, cells containing mitochondria were
more efficient than anaerobic cells. Some of these newer, unicellular
organisms grew larger and evolved into predators capable of eating
smaller cells. Their prey undoubtedly included cyanobacteria. In rare
cases, these small photosynthetic cells may have resisted digestion
after being engulfed. Inside the predator, they set up a
semi-independent existence and eventually evolved into chloroplasts.

Although such a scenario may seem far-fetched, we know that similar
partnerships exist today. For example, the unusual ciliate Paramecium
bursaria is host to many unicellular green algae in the genus
Chlorella. These "pseudochloroplasts" produce sugar molecules that are
shared with the host. If the Chlorella are experimentally removed, both
partners continue to exist independently. Without its photosynthetic
partners, however, the Paramecium becomes totally dependent , upon
external sources of food. Provided the opportunity, the Paramecium will
eat Chlorella but will not digest them, thus reestablishing the
symbiotic partnership. Paramecium bursam'a is not a unique case of
modern endosymbiosis. Many other organisms, including several
multicellular animals, also play host to photosynthetic algae or
cyanobacteria.

The most controversial claim made by Margulis is that eukaryotic
flagella evolved from small, corkscrew-shaped bacteria called
spirochetes. Many spirochetes are parasites (the best known, Treponema
pallidurn, causes syphilis). Others are free-living, found in such
exotic environments as the intestines of termites. Regardless of how
they live, these unusual bacteria swim with an undulating motion
reminiscent of the whiplike movement of eukaryotic flagella. Is this
similariti evidence for Margulis's evolutionary claim, or is it simply
a coincidence? Why not accept the more orthodox explanation that
eukaryotic flagella gradually evolved from the simpler flagella found
on many bacteria?

Margulis points out that although both types of flagella are used
for locomotion, prokaryotic and eukaryotic structures are very
different. Prokaryotic flagella consist of a single, hollow filament of
protein that spins on its axis like a tiny propeller. Eukaryotic
flagella are much larger; they contain a complex arrangement of 11
microtubules, and the entire structure is surrounded by an extension of
the cell membrane. In contrast to the spinning prokaryotic flagellum,
the eukaryotic structure propels the cell by lashing back and forth in
a whiplike fashion. Because they are so different in structure,
function, and perhaps evolutionary origin, Margulis proposes that the
eukaryotic flagellum should be referred to by a different term:
undullpodium.




Origin of Mitochondria in Eukaryotic Cells
By Kristina Penniston, 7/97

The inner organization of the living cell, consisting of specialized
organelles, makes complex forms of life possible. It is indisputable,
given the fossil records, that single-celled organisms with little or
no intercellular organization once dominated the earth. At what many
believe was the start of life (as we define it), blue-green algae ruled
the planet but went into decline after about 1.6 billion years. Sowing
the seeds of their own demise by producing oxygen which, at a critical
mass point, could no longer be absorbed by the oceans and accumulated
in the earth's atmosphere, the blue-green algae gave way to other
cell-based organisms which could grow in an oxygenated environment.
These new organisms marked the origins of the eukaryotic cell,
estimated to have occurred when the oxygen level rose to about 3% of
its present atmospheric level (Crawford and Marsh, 1995, p. 69). While
this general chronology is fairly well accepted as fact, there is
debate about how the eukaryotes arrived on the scene, specifically, how
the eukaryotic mitochondrion originated.

Strict Darwinists or proponents of natural selection theory would argue
that the blue-green algae mutated and made selectively advantageous
mutations over millions of years until, through competition and
selection, a winning combination of traits allowed the algae to survive
in the presence of oxygen, albeit as a changed life form. Others
believe that symbiosis, more specifically, endosymbiosis, was the basis
for the first eukaryote. This theory, popularized by Lynn Margulis in
her 1981 book, Symbiosis in Cell Evolution, advocates the following
chronology:

Blue-green algae produced oxygen as a by- product of photosynthesis,
allowing oxygen to build up in the atmosphere;
alongside the blue-green algae, other bacteria (prokaryotic cells)
developed and grew, some of them with aerobic capabilities;
anaerobic, heterotrophic cells (proto eukaryotes) ingested or engulfed
these aerobic bacteria and developed a mutually beneficial
relationship.
How did both species benefit? The ingested aerobic bacterium received
nutrients from the host while the host received energy from the aerobic
activity of the bacterium. While there are many applications of the
symbiosis theory of cell evolution, the subject of this discussion is
the origin and function of mitochondria in eukaryotic cells.

In the scenario presented above, the aerobic bacterium which was
ingested by the anaerobic bacterium was proto mitochondrion, in other
words, the organism which made possible the production of energy from
oxygen. Symbiosis, the relationship of mutual benefit between two
species such as the one described above, is believed by some to have
been the process by which mitochondria became organelles in eukaryotes.
Before delving into the evidence for the theory, however, the functions
and structure of the present-day mitochondrion must be addressed.
Mitochondria are the eukaryotic organelles which carry out oxidative
respiration, the final step in cellular respiration. Oxidative
respiration breaks down the pyruvate formed from glycolysis to form
carbon dioxide and produces the majority of the cell's ATP. Oxygen is
necessary for the eukaryotic cell because mitochondria use it as the
terminal electron acceptor in the electron transport chain, ultimately
resulting in a proton gradient which drives ATP synthesis. Mitochondria
are present to varying degrees in different eukaryotic cells. Cells
requiring lots of energy such as in muscle tissue and liver have
proportionately more mitochondria than cells requiring less energy such
as bone.

What is the structure of the mitochondrion? The features examined here
are size, membrane structure, protein status, and genetic information.
Mitochondria are one of the larger organelles in the eukaryotic cell,
ranging from 0.3-1.0 &m by 5-10 &m. It has two membranes, the innermost
of which folds in at many points along its perimeter in a formation
resembling a maze. These infoldings, called cristae, are the launch pad
of enzymes and electron carriers (cytochromes) responsible for electron
transport and oxidative phosphorylation. The manner in which the
cristae are arranged keeps these enzymes segregated according to their
utility, an example of the high level of organization within the
mitochondrion. Mitochondria are unique among all other organelles
because they contain their own DNA, i.e., separate from the cell
nucleus' DNA, and its configuration is circular. Ribosomes in the
mitochondrion produce some of the organelle's proteins according to its
own, independent DNA.

What is the evidence supporting the endosymbiotic theory of the
mitochondrion and the eukaryotic cell? Some of the most convincing
evidence supporting the symbiosis theory was just outlined in the
preceding paragraph on mitochondrial structure. If mitochondria were
once free-living bacteria, the thinking goes, they could be expected to
exhibit some vestigial remnants of their former condition even though
they are organelles today. Along these lines, examination of six issues
follows.

In general, mitochondria and bacteria are basically the same size. This
cannot be said about the other eukaryotic organelles.

Mitochondria have a set of double membranes, as do most bacteria; and
the lipid composition of mitochondrial membranes shows no similarities
with the eukaryotic cell cytoplasm. If mitochondria evolved inside of
proto eukaryote, their membrane composition would be expected to be of
the same material. Instead, it appears that mitochondrial membranes
more closely resemble bacterial membranes in terms of lipid composition
(Margulis, 1981, p. 217).
The inner-membrane infoldings in the mitochondria lend more credence to
the symbiosis theory. According to Margulis, the infoldings (cristae)
"are adaptations that increase the surface area of oxidative enzymes,
evolutionary analogues to the mesosomal membranes of many prokaryotes"
(Margulis, 1981, p. 208). In addition, the cristae keep the various
enzymes segregated according to use, as do bacteria.
Mitochondrial ribosomal RNA sequences bear much more in common with
bacteria than with ribosomes in the eukaryotic cytoplasm. For example,
n-formylmethionyl transfer RNA has been found to exist only in
mitochondria and bacteria (Dyer and Obar, 1985, p. 78).
Not only do mitochondria possess their own DNA, but it is circular, as
is bacterial DNA; and DNA synthesis is continuous as opposed to that of
eukaryotic nuclear DNA. Furthermore, the ratio of guanine-cytosine base
pairs in mitochondrial DNA is proportionately higher, as with bacteria,
than in eukaryotic nuclear DNA (Margulis, 1981, p. 206).
Mitochondrial division resembles bacterial reproduction, according to
Margulis. She writes, "Genetic recombination in (mitochondria) is far
more reminiscent of phage and bacterial sexuality than it is of
eukaryotic nuclear sexual behavior" (Margulis, 1981, p. 218).
A closer look at mitochondrial ribosomes reveals even more supportive
evidence for symbiosis theory. Mitochondrial ribosomes have more
similar antibiotic sensitivities with bacterial ribosomes than with
eukaryotic ribosomes. For example, cycloheximide blocks eukaryotic
ribosomes by affecting tRNA transfer but affects neither mitochondria
or bacteria. On the other hand, drugs that block prokaryotic synthesis
but not eukaryotic synthesis block mitochondrial protein synthesis as
well, e.g., erythromycin and tetracycline (Margulis, 1981, p. 217-218).

The structural analogies between mitochondria and bacteria are
compelling but not at all conclusive. Many have questioned the
plausibility of the symbiotic theory -- that there even existed a
free-living proto mitochondrion at the advent of oxygen (fossil records
aren't, of course, conclusive), that it somehow entered a proto
eukaryote, was a partner in a symbiotic relationship that eventually
resulted in proto mitochondrion yielding its autonomy to the larger
cell, giving way to the eukaryote. Is this too much to swallow? Because
evolution is, in many ways, the history of various chemical reactions
from the earthís formation to the biochemical reactions in living
cells, let us examine the plausibility of symbiotic theory.

First, it isn't inconceivable that free-living aerobic bacteria,
producing high-energy molecules such as ATP, would enter into a
relationship in which that energy, the likes of which had not existed
prior to the advent of oxygen (aerobic respiration represented a new
level of efficiency), could be used. Second, the production of all that
energy must have required an enormous input of energy, i.e., a
plentiful, available, efficient nutrient source. Third, the advent of
oxygen, a poisonous gas to the vast majority of the inhabitants of the
earth at that point, required new forms of metabolism based on a new
chemistry.

Finally, without a means to metabolize the oxygen in the atmosphere,
proto eukaryote would have a more difficult time surviving. The basis
for the symbiosis is clear: the larger, anaerobic organism provided a
steady source of nutrients as well as phospholipids for the
mitochondrial membranes (Crawford and Marsh, 1995, p. 71-72) to the
smaller, aerobic bacterium. In return, the energy provided by the
respiration of oxygen allowed the host to survive and further adapt to
the world's new conditions.

The symbiotic theory is bolstered by natural, observed examples of
symbiotic relationships. Certain marine fish are able to emit light due
to the presence of luminous bacteria in their interior. These luminous
bacteria also live freely in seawater, but do not present luminosity
(Dyer and Obar, 1985, p. 127). Other categorical examples of symbiosis
are represented by the relationships between various fungi and
cyanobacteria, algae and plants, and bacteria and mammals (Margulis,
1981, p. 165). While the transformation of these symbionts to
organelles is quite a leap if provided only with examples of
present-day symbiotic relationships such as those above, it must be
remembered that this transformation, if indeed it transpired, occurred
over millions of years. Moreover, it is doubtful that we humans, during
the brief tick of the evolutionary clock in which we have existed, have
experienced the kind of change to our environment that the advent of
oxygen represented in its time. We cannot possibly know, with our
fleeting existence on Earth, what kinds of evolutionary leaps and
bounds are possible with such monumental change.

For the academic/philosophical reasons just described and with the
physical and chemical facts gleaned through scientific experimentation
in mind, one cannot dismiss the theory that mitochondria evolved as
organelles in the eukaryotic cell from free-living, aerobic bacteria in
a newly-oxygenated world. Questions do remain, however, and should
provide for interesting study. How (and from what) did proto
mitochondrion evolve alongside the blue-green algae? By what means did
proto mitochondrion enter the larger, anaerobic cell? Did examples of
free-living proto mitochondrion survive? Do they or their progeny exist
today? Are other eukaryotic organelles also derived from free-living
organisms? But for now, the evidence demonstrates that the symbiosis
theory of cell evolution is on sound footing.

REFERENCE CITATIONS

1. Crawford, Michael and David Marsh, 1995. Nutrition and Evolution, p.
65-83. Keats Publishing, Inc., New Canaan, CT.

2. Dyer, Betsey Dexter and Robert Obar (editors), 1985. The Origin of
Eukaryotic Cells, Van Nostrand Reinhold Company, Inc., NY. Papers by:

a.) Goksøyr, J., 1967, "Evolution of Eucaryotic Cells;"

b.) Schwartz, R.M. and M.O. Dayhoff, 1978, "Origins of Prokaryotes,
Eukaryotes, Mitochondria, and Chloroplasts;"

c.) Raven, P.H., 1970, "A Multiple Origin for Plastids and
Mitochondria;"

d.) Doolittle, W.F., 1980, "Revolutionary Concepts in Evolutionary Cell
Biology;" and

e.) Smith, D.C., 1979, "From Extracellular to Intracellular: The
Establishment of a Symbiosis."

3. Margulis, Lynn, 1981. Symbiosis in Cell Evolution, p. 206-227. W. H.
Freeman and Company, San Francisco.

4. Prescott, L.M., J.P. Harley and D.A. Klein, 1996. Microbiology,
third edition. Wm. C. Brown

Publishers, Dubuque, IA.



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