Higher animals have a number of complex systems in
their bodies. These systems depend on specialized proteins which perform
unique functions. Interestingly, many of the genes which produce these
proteins belong to gene families whose origins date back to early prokaryotic
and eukaryotic cells. Many of the most complex systems in higher animals
owe their origins to the evolutionary events in their ancient unicellular
MOLECULES OF THE NERVOUS SYSTEM
The nervous system might have originated in primitive sensory cells which
could stimulate local muscle contraction. The ancestral neurons might
have been simpler neurosecretory cells which would develop the ability
to conduct impulses later their evolution. Given that gut and pituitary
hormones can be made in the brain and that neuropeptides can be made outside
the nervous system, there is reason to believe that the nervous and endocrine
systems are evolutionarily linked (LeRoith, 1981).
In the nervous and endocrine systems, a variety of signals must be sent
between cells. A number of the signaling molecules found in the nervous
and endocrine systems are known in organisms which lack these systems.
Bacteria such as E. coli synthesize a protein similar to insulin and several
protozoans are known to make peptides similar to adrenocorticotropic hormone,
ß-endorphin, and dynorphin (LeRoith, 1981). Ciliates can possess
receptors for substances which effect neurons such as ACh, neurepinephrine,
and epinephrine. A mating pheromone in the protozoan Blepharisma resembles
serotonin. The use of cAMP in signal transduction is involved in processes
other than neural function and cAMP can even serve as an extracellular
signal in slime molds (Mackie, 1990). Some plants use the signaling molecules
glycine, GABA, glutamate, and ACh (Mackie, 1990). The simple nervous system
of cnidarians includes the use of neuropeptides (Mackie, 1990).
In essence, the nervous system runs on electricity. Thought is electrical.
Remembering your grandmother, preferring one outfit over another based
on your favorite color, and recognizing the voice of your best friend
all require that neurons conduct electricity. The ability of neurons to
conduct electrical messages (action potentials) along their axons depends
on their ability to generate resting electrical potentials across their
cell membranes. This is a characteristic of most cells in the human body
and many unicellular organisms as well. Some ciliates, such as Paramecium
and Opalina, generate negative resting membrane potentials which, when
stimulated, produce an influx of calcium which results in a reversal of
the ciliary beat. Membrane depolarization results in the luminescent response
in the dinoflagellate Noctiluca. Action potentials are known in the alga
Nitella, the sensitive plant Mimosa and the venus flytrap (Prosser, 1973,
p. 457). Yeast possess a number of genes which direct vesicle movement
and CAM kinase II (which is essential for the formation of long term memory
in vertebrates) (Mineta, 2003).
Although the ability to conduct electricity is most commonly identified
with the nervous and muscular systems, other cell types can carry electrical
messages as well. This more primitive transport of electrical messages
may provide insight into the evolution of nervous tissue. The epithelia
of ctenophores and jellyfish can conduct electrical messages without neurons.
This neuroid conduction is known in epithelial and muscle sheets of higher
animals as well (Hoar, 1983, p. 133-4). Electrical coupling is known to
occur between the embryonic cells of squid, starfish, fish, and tadpoles.
For example, in tadpole embryos, action potentials travel through the
skin before nerves develop. Intercellular junctions (such as gap junctions)
allow electrical coupling between cells in fly salivary glands, toad bladders,
mouse livers, and malphigian tubes (Prosser, 1973, p. 461-2). Gap junctions
allow electrical flow through cardiac and smooth muscle. Many neurons
are linked by electrical synapses and these synapses are known between
neurons in worms, mollusks, and arthropods and in vertebrates from fish
through mammals. (Prosser, 1973, p. 483).
A neuron's ability to create resting and action potentials rests in
its ability to transport ions, particularly potassium and sodium ions.
Potassium channels are ancient proteins which evolved in organisms long
before the ability to transmit electrical messages. Prokaryotes (eubacteria
and archea) are known to possess potassium channels and these channels
are homologous to those found in eukaryotes (Jiang, 2002). Eukaryotic
channels retain their function when the eukaryotic channel pore is replaced
by the pore from prokaryotic channels (Lu, 2001). As pictured below, the
potassium channel is not only the simplest of the voltage regulated ion
channels, its 6-transmembrane region structure (with the fourth unit being
the voltage-regulated portion) is the prototype for the more complex sodium
and calcium channels which are composed of four separate homologous regions.
The simplest potassium channels form tetramers using four subunits of
the same gene. (Darnell; Yellen, 2002).The potassium, sodium, and calcium
voltage regulated channels are pictured below (after Darnell, p.782).
Neurons must be able to respond to a wide variety of neurotransmitters,
neuropeptides, hormones, light, olfactory stimuli, taste stimuli, and
other stimuli. Interestingly, most of these phenomena are perceived by
the use of the members of one gene family, the G-protein coupled receptors.
G-protein coupled receptors are used in many cell types other than those
of the nervous system and evolved very early in the history of life, long
before the evolution of animals. This superfamily of proteins share a
set of 7 hydrophobic transmembrane regions connected by hydrophilic sections
which form either intracellular or extracellular loops. This is a very
old family found even in bacteria; bacteriorhodopsin is homologous to
GPCRs of higher organisms although exon shuffling has changed the order
of the transmembrane regions. Gene duplication had produced many of the
subfamilies of the G proteins (Suga, 1999).
MOLECULES OF THE MUSCULAR SYSTEM
There are two major proteins responsible for the contraction of a muscle
cell, actin and myosin. Myosin proteins possess a pivoting head which,
after binding to ATP molecules for energy, can attach to specific sites
on actin molecules, pivot, and return to their original position. Although
these proteins are essential components of vertebrate muscle, they evolved
in early cells are conserved throughout the groups of eukaryotes. Actin
proteins are highly conserved proteins which constitute the majority of
the eukaryotic cytoskeleton and can compose 10-20% of the total cellular
protein of a non-muscle eukaryotic cell. These thin filaments are involved
in organelle transport, cell motility, and cytokinesis (OMIM; Hoar, 1983).
The shape of all eukaryotic cells is determined by the shape of the protein
cytoskeleton. These thin filaments are involved in organelle transport,
cell motility, and cytokinesis. While yeast possess only one known actin
gene, multiple genes are known from all protozoa, plants, and animals
studied (Hightower, 1986). Although actin was formerly thought to be unique
to eukaryotes, it is now evident that bacteria possess several homologs
of actin, such as MreB and ParM, which can polymerize into filaments.
There are 11 classes of myosin molecules in the myosin superfamily that
are known from animals, plants, fungi, and protists. Some of the predominant
myosins in amoeba are conserved in vertebrates. In addition to the conventional
myosins found in vertebrate muscle, many are referred to as unconventional
myosins which act as molecular motors which move along actin molecules.
Seven of the known 11 classes of unconventional myosin molecules are found
in vertebrates. (Mooseker, 1995).
MOLECULES OF THE ENDOCRINE SYSTEM
The hormones of the endocrine system cannot affect the cells of the body
unless the cells of the body have receptors which can perceive them. Many
hormone receptors are G protein coupled receptors. This superfamily of
proteins shares a set of 7 hydrophobic transmembrane regions connected
by hydrophilic sections which form either intracellular or extracellular
loops. This is a very old family found even in bacteria; bacteriorhodopsin
is homologous to GPCRs of higher organisms although exon shuffling has
changed the order of the transmembrane regions. Gene duplication had produced
many of the subfamilies of the G proteins and protein tyrosine kinases
before the lineages leading to modern sponges separated from those leading
to higher animals (Suga, 1999). Unicellular yeast respond to mating pheromones
through G-protein coupled receptors, reminiscent of homone-receptor interactions
of animals (Blumer, 1988).
MOLECULES OF THE CARDIOVASCULAR SYSTEM
Hemoglobins are heme-containing proteins which reversibly bind oxygen.
Hemoglobin is not unique to higher animals with circulatory systems: a
variety of hemoglobins are known in bacteria, fungi, higher plants, most
invertebrates and all vertebrates. All of them belong to the same globin
gene family, having evolved from a single ancient ancestral protein. In
bacteria and yeast, multi-domain proteins combine hemoglobin with other
domains to produce proteins novel proteins such as flavohemoglobins. Bacterial
flavohemoglobin can remove NO (nitric oxide) by reacting it with oxygen
to form nitrate. When oxygen is not present, flavohemoglobin removes NO
by promoting the conversion of N2O. Thus these molecules offer protection
from NO in both aerobic and anaerobic conditions. In the ancient earth
(and in the communities of deep sea vents), NO would have been far more
abundant than oxygen.Carbonic anhydrase existed long before vertebrate
circulatory systems, given that it is known from bacteria and plants (Hoar,
1983). The diverse carbonic anhydrase genes in living organisms, including
the multiple genes which can be expressed in mammals, belong to one gene
family (Tufts, 2003).
MOLECULES OF THE DIGESTIVE SYSTEM
Bacteria and protists can release digestive enzymes into their environment
and, after chemical digestion, absorb the simpler molecules.Serine proteases
are a large family of enzymes in the human genome which function in diverse
physiological processes ranging from digestion to coagulation (OMIM; Yosef,
2003). This is an ancient gene family which includes eubacterial digestive
enzymes and the vertebrate digestive enzymes trypsin and chymotrypsin.
MOLECULES OF THE URINARY SYSTEM
The metabolic pathway that humans use to produce the urea excreted by
the urinary system is called the arginine-urea pathway since it produces
arginine for protein synthesis in addition to producing urea. It has other
uses in the excretion of wastes since the production of ammonia can combat
acidosis since ammonia can bind hydrogen ions and be excreted from the
kidneys. Microorganisms use this pathway for the production of arginine
only. Birds and insects lack this pathway and must include arginine in
their diets. Thus the same metabolic pathway can be both nutritional and
excretory. Some aspects of the arginine-urea metabolic pathway crucial
for the human urinary system can be found in at least some members of
all living groups, including bacteria, some reptiles, and insects. Some
gastropods make use of a separate pathway to produce ammonia involving
purine metabolism. In other organisms, from bacteria through humans, this
second pathway serves only to synthesize purines as components of nucleotides.