Molecular Biology of the Cell - Volume 1 - Alberts B., Bray D., Lewis J., Raff M., Roberts K., Watson J. 1994

Introduction to Cell Biology
Cell Evolution
From Prokaryotes to Eukaryotes

It is hypothesized that all currently Living organisms are descended from a single primordial Cell that emerged several billion years ago. Having outcompeted its rivals, this cell initiated the processes of Cell Division and evolution that ultimately clothed the Earth in greenery, transformed its atmospheric composition, and made it the cradle of intelligent life. This would appear to be the only plausible explanation for the "family resemblance" shared by all organisms. A major milestone marks this evolutionary path: approximately 1.5 billion years ago, a transition occurred from small Cells with relatively simple internal structures—known as prokaryotes, which include various Bacteria—to much larger and considerably more complex Eukaryotic cells, akin to those of higher animals and plants.

1.2.1. Prokaryotic Cells feature a simple Structure yet vary in biochemical properties [7]

Bacteria are the simplest organisms, found in the vast majority of natural habitats. They typically appear as spherical or elongated cells measuring a few micrometres across (Fig. 1-13). As a rule, they possess a rigid protective covering called a Cell wall, beneath which lies The Plasma Membrane enclosing a single cytoplasmic compartment containing DNA, RNA, Proteins, and small molecules. Under an Electron microscope, the contents of such cells resemble a matrix of varying density devoid of distinctly organized internal structures (see Fig. 1-8, A).

Bacteria are tiny and capable of rapid proliferation through simple binary division. When nutrients are abundant, "survival of the fittest" generally translates to the survival of those that divide the fastest. Under optimal conditions, a Introduction/4.html">Prokaryotic Cell can divide every 20 minutes, thereby generating up to 5 billion cells (roughly equivalent to the human population of the Earth) in under 11 hours. Thanks to this capacity for rapid division, bacterial populations readily adapt to environmental changes. For instance, in laboratory settings, a bacterial population maintained in a large vessel can acquire The ability to utilize new types of sugars as a carbon source within a few weeks, driven by spontaneous Mutations and natural Selection.

In nature, bacteria occupy an unimaginable array of ecological niches, and their biochemical makeup is correspondingly diverse. They are generally divided into two groups: eubacteria—common forms inhabiting soil, Water, and other organisms—and archaebacteria, which thrive in extreme environments such as swamps, deep ocean trenches, hypersaline waters, and acidic hot springs (Fig. 1-14).

Class="center">

Fig. 1-13. Selected prokaryotic cells shown at the same scale.

Fig. 1-14. Evolutionary relationships among modern bacteria (arrows indicate putative evolutionary pathways). THE ORIGIN OF eukaryotic cells is discussed later in the text.

Certain species of bacteria are capable of subsisting on virtually any organic molecules—sugars, Amino Acids, fats, CARBOHYDRATES, Polypeptides, and Polysaccharides. Some can even derive carbon atoms from CO₂ and nitrogen atoms from N₂. Despite their relatively simple architecture, bacteria have inhabited the Earth longer than any other organisms and outnumber all other cell types combined.

1.2.2. The Evolution of Metabolic Pathways

A bacterium growing in a salt solution with glucose as its sole carbon source must carry out a multitude of Chemical Reactions. Not only must it extract chemical energy from glucose to fuel numerous vital processes, but it must also utilize the carbon atoms to synthesize all the organic molecules required by The Cell. These reactions are catalyzed by hundreds of Enzymes operating sequentially in chains of chemical reactions, wherein the product of one reaction serves as the substrate for the next. Such chains of enzymatic reactions, termed metabolic pathways, are discussed in the following chapter.

Initially, when life on Earth first arose, metabolic reactions were presumably unnecessary: cells could live and grow by feeding directly on the surrounding molecules—the legacy of the primordial soup. As these natural reserves dwindled, organisms that could synthesize enzymes to produce organic molecules would have gained a massive selective advantage. It is believed that the cell's repertoire of enzymes gradually expanded in this manner, ultimately giving rise to the metabolic pathways seen in modern organisms. Two potential scenarios for the evolution of Metabolic pathways are illustrated in Fig. 1-15.

If metabolic pathways evolved through the sequential addition of novel enzymatic reactions to pre-existing ones, then, much like the oldest tree rings in a trunk cross-section, the most ancient reactions should reside closest to the center of the "metabolic tree"—where the most essential molecular building blocks are synthesized. Reactions involving sugar phosphates firmly occupy this central position in METABOLISM, right at the core of which lies The sequence of reactions known as Glycolysis, capable of breaking down glucose in the absence of oxygen (i.e., anaerobically). The earliest metabolic pathways must have been anaerobic, given the absence of oxygen in the atmosphere of the primitive Earth. Virtually all living cells engage in glycolytic reactions accompanied by The production of adenosine triphosphate, or ATP—a compound utilized across all cell types as a readily accessible source of chemical energy.

Fig. 1-15. Schematic illustrating two possible Mechanisms for the emergence of metabolic pathways. The cell on the left has access to a supply of related compounds (A, B, C, D) generated through prebiotic synthesis. One of these compounds (D) is metabolically useful. As supplies of this compound become depleted, selection favors cells that "learn" to synthesize a new enzyme catalyzing The formation of D from C. The successive repetition of such steps could drive The Development of essential metabolic pathways. In the cell shown on the right, the metabolically useful compound A is abundant. Over the course of evolution, an enzyme emerges that fortuitously proves capable of converting compound A into compound B. The cell subsequently undergoes further modifications allowing it to exploit this novel substance. The eventual appearance of additional enzymes can ultimately lead to the establishment of a long reaction chain.

Hundreds of other Chemical reactions are linked to these central sugar-phosphate transformations. Some of these are responsible for synthesizing small molecules, many of which are subsequently used in further reactions to build larger, Organism-specific polymers. Other reactions participate in breaking down complex food molecules into simpler chemical building blocks. One of the most striking features of all these reactions is their ubiquity across every type of organism. Naturally, differences do exist: many specialized metabolic products are restricted to specific genera or species. For example, The amino acid Lysine, common to most organisms, is synthesized via different pathways in bacteria, Yeasts, and green plants, and is not synthesized at all in higher animals. Nevertheless, in a broader sense, the vast majority of reactions and the enzymes catalyzing them are characteristic of all living things, from bacteria to humans. It is therefore believed that the primitive ancestral cells that gave rise to all life already carried out these fundamental reactions. As organisms diverged, the enzymes catalyzing core metabolic reactions were gradually modified without altering their primary function. Consequently, the Amino acid sequences of the same type of enzyme across various modern organisms harbor invaluable information regarding the evolutionary relationships among these species. Data acquired in this manner align well with findings from other research fields, such as paleontology. An even richer source of information is encoded within the DNA nucleotide sequences of modern cells. Comparing highly conserved sequences that dictate essential Functions (and thus evolve very slowly) sheds light on the relationships among long-diverged organisms (Fig. 1-16). More rapidly evolving sequences can be employed to evaluate Evolutionary Processes within closely related species (Fig. 1-17). It is hoped that the application of these techniques will enable researchers to trace the course of evolution with unprecedented precision.

Fig. 1-16. Evolutionary relationships among organisms based on sequencing data from small subunit ribosomal RNA genes. These genes contain highly conserved sequences that evolve so slowly they can be used to "measure" phylogenetic affinities across all Major Groups of living organisms. These data indicate that during the evolution of eukaryotic cells, the plant, animal, and fungal lineages diverged from a common ancestor relatively late. (From M. L. Sogin, H. J. Elwood, J. H. Gunderson, Proc. Natl. Acad. Sci. USA, 83, 1383-1387, 1986.)

Fig. 1-17. Is humans' closest living relative the gorilla or the orangutan? This question can be addressed by analyzing the DNA sequences of these species and constructing the Phylogenetic Tree shown at the top of the figure. Mitochondrial DNA is typically employed to clarify phylogenetic affinities among closely related organisms because it evolves roughly 5 to 10 times faster than nuclear DNA. The bottom portion of the figure displays the first 75 nucleotide sequences of a single Gene (the mitochondrial gene encoding a subunit of NAD dehydrogenase) for each of the species. Colored letters highlight sites where the gorilla and orangutan differ from humans. Rectangles beneath The nucleotide sequences denote the corresponding amino acids in the proteins. Amino acid names that differ from the human counterparts are also highlighted in color. The analysis reveals that the gorilla sequence differs from the human sequence by 10%, whereas the orangutan differs by 17%. Assuming these differences stem from random mutations occurring at a constant rate in each species Lineage, one can derive the phylogenetic tree shown in diagram A. (Data from W. M. Brown, E. M. Prager, A. Wang, A. C. Wilson, J. Mol. Biol., 18; 225-239, 1982.)

1.2.3 Cyanobacteria are capable of fixing CO₂ and N₂

The earliest stages of metabolism evolved to compensate for the depletion of organic molecules produced under prebiotic conditions. What happened once these natural reserves were fully exhausted? Under these circumstances, organisms capable of utilizing atmospheric carbon and nitrogen atoms (in the form of CO₂ and N₂) would have gained a substantial selective advantage. However, despite their Abundance, carbon dioxide and molecular nitrogen are chemically very stable. Converting them into an assimilable form (such as organic molecules like simple sugars) demands vast amounts of energy and a complex sequence of chemical reactions.

To utilize CO₂, Photosynthesis evolved as a mechanism whereby Carbon dioxide is converted into Organic compounds driven by solar radiation energy. The interaction of sunlight with the pigment molecule chlorophyll elevates an electron to a higher energy state. The energy released when this electron drops back to a lower energy level is harnessed by Protein Complexes to drive chemical reactions.

Most likely, one of the earliest light-driven reactions was the phosphorylation of NUCLEOTIDES to yield ATP, an energy-rich compound. Another pivotal milestone in evolution was the generation of "reducing power" (reducing equivalents). The carbon and nitrogen atoms in atmospheric CO₂ and N₂ reside in an inert, oxidized state; one way to render them sufficiently reactive to participate in Biosynthesis is to reduce them—that is, to transfer electrons to them. Reduction proceeds as follows: chlorophyll harnesses sunlight energy to strip electrons from weak electron Donors and transfer them to strong electron donors, which in turn are used to reduce CO₂ and N₂. An analysis of photosynthetic mechanisms in modern bacteria suggests that H₂S was among the earliest electron sources, with elemental sulfur as its metabolic byproduct. A much more complex, yet ultimately far more advantageous process of extracting electrons from H₂O evolved significantly later, resulting in the accumulation of oxygen as a byproduct in the Earth's atmosphere.

In the modern world, the primary pathway by which carbon and nitrogen are incorporated into organic molecules and enter the biosphere is driven by the METABOLIC ACTIVITY OF cyanobacteria (also known as blue-green Algae). This group comprises some of the most autonomous organisms alive today. They are capable of "fixing" CO₂ and N₂, surviving solely on water, air, and sunlight—mechanisms that, in their broad outlines, appear to have remained unchanged for over 1 billion years. Together with other bacteria possessing some of these capabilities, cyanobacteria established the conditions that enabled more complex life forms to evolve: once a single group of organisms succeeded in synthesizing the entire range of cellular organic components from inorganic substances, other life forms became able to thrive by feeding on these primary producers and their metabolic byproducts.

1.2.4. Bacteria Can Carry Out Aerobic Oxidation of Food Molecules

Many people today are rightly concerned about The impact of human activity on the environment. Yet in the past, other organisms—albeit much more slowly—also brought about radical changes in Earth's conditions. This is most clearly illustrated by the COMPOSITION OF THE atmosphere, which, following the advent of photosynthesis, transformed from a gas mixture virtually devoid of molecular oxygen into one containing 21% oxygen.

Given oxygen's high chemical reactivity and its ability to react with most cytoplasmic components, it is reasonable to conclude that oxygen was likely toxic to many early organisms (much as it is to many modern anaerobic bacteria). However, it is precisely because of this high reactivity that oxygen can serve as a potent "supplier" of chemical energy, and it is hardly surprising that evolution co-opted this property. Oxygen allows living cells to oxidize food molecules much more completely. For example, in the absence of oxygen, glucose can be broken down only into lactic acid or ethanol, the end Products of Anaerobic glycolysis. In the presence of oxygen, however, glucose is completely degraded to H₂O and CO₂. This pathway yields significantly more energy from every gram of glucose. The energy released during the aerobic oxidation of food molecules, commonly referred to as Respiration, is used to synthesize ATP, much as photosynthetic organisms generate ATP using solar energy. In both cases, a series of sequential electron-transfer reactions creates an ion concentration gradient of H⁺ across small, membrane-bounded compartments. The resulting H⁺ concentration gradient then drives the synthesis of ATP. Today, respiration is characteristic of the vast majority of organisms, including most prokaryotes.

1.2.5. Eukaryotic cells contain Several Distinct Organelles

How did the accumulation of molecular oxygen in the atmosphere affect the anaerobic organisms that originally sparked life on Earth? In an oxygen-rich world they could not utilize, such organisms found themselves at a severe disadvantage. Some undoubtedly perished. Others either evolved the capacity for respiration or retreated to ecological niches virtually devoid of oxygen, continuing their anaerobic lifestyle there. In all likelihood, a third class of organisms adopted a far subtler and immeasurably more consequential survival strategy. It is believed that organisms of this group entered into a symbiotic relationship with aerobic cells, eventually forming a stable association. This provides the most compelling explanation for the origin of modern eukaryotic cells (Scheme 1-1), which are the primary focus of this book.

By definition, and unlike prokaryotes, eukaryotic cells possess a nucleus (from the Greek *karyon*). The Nucleus, which houses the bulk of the cellular DNA, is enclosed by a double membrane (Fig. 1-18). Thus, the DNA-containing compartment is segregated from the rest of the cell—the Cytoplasm—where the majority of metabolic reactions take place. The cytoplasm itself contains a variety of distinct organelles. Among these, two types stand out in particular: Mitochondria and Chloroplasts (Figs. 1-19 and 1-20). Each of these organelles is surrounded by its own double membrane, chemically distinct from the nuclear envelope. Mitochondria are an almost universal component of eukaryotic cells, whereas chloroplasts are found exclusively in photosynthetic eukaryotes—that is, in plant cells, but not in animal or fungal cells. Both organelles are believed to be of symbiotic origin.

Scheme 1-1. Major organelles of eukaryotic cells.

Fig. 1-18. The nucleus contains the majority of a Eukaryotic Cell's DNA. The nucleus is clearly visible in this electron micrograph of a thin section of a mammalian cell. (Courtesy of Daniel S. Friend.)

Fig. 1-19. Electron micrograph of a moss chloroplast, showing the intricate network of internal membranes. Flattened chlorophyll-containing membrane sacs are stacked into grana (G). This chloroplast also contains large starch deposits (S). (Courtesy of J. Burgess.)

Fig. 1-20. Mitochondria carry out the oxidative breakdown of nutrients in all eukaryotic cells. As seen in this electron micrograph, their outer membrane is smooth, whereas the inner membrane is highly folded. (Courtesy of Daniel S. Friend.)

1.2.6. Eukaryotic Cells Depend on Mitochondria for Oxidative Metabolism

Mitochondria share many similarities with free-living prokaryotes: for instance, they resemble bacteria in shape and size, contain DNA, synthesize proteins, and reproduce by fission. Disrupting eukaryotic cells and fractionating their components demonstrates that mitochondria are responsible for cellular respiration and that this process occurs nowhere else in the cell. Without mitochondria, animal and fungal cells would be anaerobes, relying for their energy needs on the relatively inefficient and archaic process of glycolysis. Many modern bacteria can respire via a mechanism strikingly similar to mitochondrial respiration, giving strong reason to believe that eukaryotic cells descended from primitive anaerobic organisms that survived an oxygen-rich world by engulfing aerobic bacteria. They maintained these bacteria in a symbiotic state to harness their ability to consume atmospheric oxygen and generate energy. Analysis of certain modern organisms Supports the plausibility of this evolutionary scenario. Several hundred species of single-celled eukaryotes resemble the hypothetical ancestral eukaryote in that they inhabit oxygen-depleted environments (such as the guts of animals) and completely lack mitochondria. Recent nucleotide sequence comparisons suggest that one group of such organisms, the microsporidians, diverged very early in evolution from the lineage leading to other eukaryotes. Another eukaryote, the amoeba *Pelomyxa palustris*, although lacking mitochondria, nevertheless performs oxidative metabolism by "hosting" aerobic bacteria in its cytoplasm in a permanent symbiotic relationship. Thus, the existence of microsporidians and *Pelomyxa* illustrates the reality of the two key evolutionary stages in The history of eukaryotes—a lineage to which we ourselves belong.

The acquisition of mitochondria must have had profound consequences. For example, in prokaryotic cells, the plasma membrane is intimately involved in energy generation, whereas in eukaryotic cells, this vital function is delegated to mitochondria. It seems highly probable that relieving the eukaryotic plasma membrane of this duty enabled it to acquire new properties. In particular, because eukaryotic cells do not need to maintain a steep H⁺ gradient across their plasma membrane (which prokaryotes require for ATP production), they became free to utilize controlled changes in plasma membrane ion permeability for cellular signaling. Consequently, Ion Channels emerged in the plasma membrane concurrently with the rise of eukaryotes. Today, in higher organisms, these channels mediate complex electrical signaling processes (such as those in The Nervous system), while in single-celled free-living eukaryotes like Protozoa, they largely dictate behavioral responses (see below).

1.2.7. Chloroplasts Are Descendants of "Captured" Prokaryotic Cells

Chloroplasts carry out photosynthesis in much the same way as cyanobacterial prokaryotes, absorbing sunlight via membrane-bound chlorophyll. Some chloroplasts closely resemble cyanobacteria in structure, sharing comparable sizes and similar arrangements of chlorophyll-bearing membrane layers (Fig. 1-20). Furthermore, chloroplasts have been shown to multiply by division, and their DNA nucleotide sequences are nearly identical to specific Regions of the bacterial chromosome. All this suggests that chloroplasts and cyanobacteria share a common ancestor, and that chloroplasts originated from prokaryotes once "captured" by eukaryotic cells. These prokaryotes performed photosynthesis for their host cells in exchange for shelter and nourishment. The Symbiosis of photosynthetic cells with other cell types is a widespread phenomenon, and A number of modern eukaryotes harbor genuine cyanobacteria within them (Fig. 1-21).

Fig. 1-21. An organism closely related to modern cyanobacteria, yet acting as an obligate symbiont of another cell (together, the two organisms are known as *Cyanophora paradoxa*). The "cyanobacterium" is shown in The process of division. (Courtesy of Jeremy D. Pickett-Heaps.)

Fig. 1-22. Hypothesis for the origin of eukaryotes via the symbiosis of aerobic and anaerobic prokaryotes

Table 1-1. Comparison of Prokaryotic and Eukaryotic Organisms

Figure 1-22 illustrates the evolutionary origin of eukaryotes According to the symbiotic theory. It should be noted that while mitochondria and chloroplasts share certain similarities with modern aerobic bacteria and cyanobacteria, they differ from them in many respects. For example, The amount of DNA in these organelles is very small, and most of their constituent molecules are synthesized outside the organelles and subsequently imported into them. If mitochondria and chloroplasts indeed originated from symbiotic bacteria, we must conclude that they have undergone significant evolutionary changes and have become highly dependent on their hosts.

Modern eukaryotes are characterized not only by the presence of mitochondria, but also by a whole range of features that distinguish them from prokaryotes (Table 1-1). Together, these characteristics endow eukaryotic cells with a vast array of potential capabilities, and it is difficult to say which of them arose first. Notably, a crucial step in evolutionary history was the appearance of mitochondria in anaerobic eukaryotic cells, as they provided the cell with an efficient energy source that could be harnessed to drive more complex functions.

1.2.8. Eukaryotic Cells Contain Many Different Internal Membranes

The volume of eukaryotic cells is typically 1,000 times or more greater than that of prokaryotic cells. Consequently, eukaryotic cells contain a much larger quantity of diverse cellular material; for instance, the DNA content of human cells is about 1,000 times that of bacterial cells. It is well established that a number of vital reactions—associated with the uptake of raw metabolic Materials and the release of corresponding products into the extracellular space—occur at the membrane. This is why the large volume of eukaryotic cells necessitates a substantial increase in their membrane surface area compared to prokaryotic cells. However, according to the laws of geometry, as an object simply increases in size, its volume increases as the cube of its linear dimension, whereas its surface area increases only as the square. Therefore, to maintain the necessary surface-area-to-volume ratio, large eukaryotic cells must expand their surface area through infoldings, folds, and other complex modifications of membrane shape.

Membrane complexity is one of the defining features of all eukaryotic cells. Membranes surround the nucleus, mitochondria, and (in plants) chloroplasts. They form the labyrinth of The endoplasmic reticulum (Figure 1-23), where Lipids, Membrane Proteins, and material destined for export from the cell are synthesized. Membranes also form stacks of flattened vesicles that constitute the Golgi apparatus (Figure 1-24), which is likewise involved in the synthesis and transport of various organic molecules. Furthermore, membranes enclose Lysosomes, which contain a store of enzymes necessary for intracellular Digestion, thereby protecting the cell's own proteins and Nucleic Acids from the action of these enzymes. Similarly, membranes surround Peroxisomes, where dangerous, highly reactive peroxides are generated and broken down during The oxidation of various molecules. Membranes also form small vesicles and large, fluid-filled vacuoles (in plants). All of these membrane-enclosed structures correspond to distinct cytoplasmic compartments. Collectively, they occupy nearly half the volume of a typical living cell. The cytoplasmic compartment excluding all membrane-enclosed organelles is commonly referred to as the Cytosol.

Figure 1-23. Electron micrograph of a thin section of a mammalian cell, showing smooth and rough endoplasmic reticulum (ER). Regions of the smooth ER are involved in Lipid Metabolism, while regions of the rough ER, studded with Ribosomes, are sites of protein synthesis. Synthesized proteins leave the cytosol and enter other cellular compartments. (Courtesy of George Palade.)

Figure 1-24. Electron micrograph of a mammalian cell section, showing the Golgi apparatus. This structure consists of several layers of flattened membrane-bound sacs (see also Scheme 1-1). The Golgi apparatus is involved in the synthesis and packaging of material destined for cellular secretion, as well as in The transport of Newly synthesized proteins to their designated cellular compartments. (Courtesy of Daniel S. Friend.)

All the membrane structures listed above are located inside the cell. How, then, can they influence its surface area? The answer lies in the exchange that takes place between the intracellular membrane-enclosed structures and the external environment. This exchange is mediated by two processes unique to eukaryotic cells: Endocytosis and Exocytosis. In endocytosis, patches of the plasma membrane invaginate and pinch off to form cytoplasmic membrane vesicles containing substances that were present in the external environment or adsorbed onto the cell surface. In this way, quite large particles and even whole cells can enter the cytoplasm (phagocytosis). Exocytosis is the reverse process, whereby intracellular membrane vesicles fuse with the plasma membrane, thereby releasing their contents into the extracellular medium. Through this mechanism, deeply internal, membrane-enclosed compartments effectively increase the cell's surface area available for metabolic exchange with the outside world.

As we will see in subsequent chapters, the various membranes and membrane-enclosed compartments of eukaryotic cells have become highly specialized: some are dedicated to secretion, others to absorption, and still others to specific biosynthetic processes, and so on.

1.2.9. Eukaryotic Cells Have a Skeleton

The larger a cell is, and the more complex and specialized its internal structures, the greater the need to control the position and movement of these structures. All eukaryotic cells possess an internal skeleton, or cytoskeleton, which determines cell shape, motility, and the translocation of organelles from one part of the cell to another. The cytoskeleton is formed by a network of protein filaments. The most prominent among these are Actin filaments and microtubules (Figure 1-25), which evidently arose very early in evolution, as they are found in virtually unchanged form across all eukaryotes. Both are involved in MECHANISMS OF CELL motility; for instance, actin filaments mediate Muscle contraction, while microtubules serve as the primary structural and force-generating elements driving the beating of Cilia and flagella—long, whip-like projections On the surface of certain cells.

Figure 1-25. Micrograph obtained using the deep-etching technique, showing the network of actin filaments underlying the plasma membrane of an animal cell. (Courtesy of John Heuser.)

Actin filaments and Microtubules are also essential for the internal movements that take place within the cytoplasm of eukaryotic cells. For example, microtubules forming the mitotic spindle are a critical component of the machinery ensuring the accurate distribution of DNA during eukaryotic cell division. Without microtubules, eukaryotic cells simply could not reproduce, as movement by simple diffusion alone would be far too slow or too disorganized. It is thought that most eukaryotic organelles are directly or indirectly attached to the cytoskeleton and can move only along its track-like elements.

1.2.10. The Kingdom of Protists Includes the Most Complex Known Cells

The extreme complexity that a single eukaryotic cell can achieve is best illustrated by protists (Figure 1-26). These are free-living Unicellular Eukaryotes that have evolved via multiple phylogenetic pathways (see Figure 1-16) and exhibit an extraordinary diversity of forms and behaviors: they can be photosynthetic or predatory, motile or sessile. They are often characterized by complex structures, such as sensory bristles, photoreceptors, flagella, FOOT-like pseudopodia, oral apparatuses, stinging darts, and muscle-like bundles of contractile fibers. Although all protists are unicellular, they can be as intricately organized as many Multicellular Organisms. This is especially true of the group of protists known as protozoa, or "first animals."

Didinium is a predatory protozoan. It has a rounded body about 150 µm in diameter, ringed by two bands of cilia, with a flattened anterior end bearing a single snout-like protrusion (Figure 1-27). Didinium swims rapidly through the water propelled by the synchronous beating of its cilia. Upon encountering suitable prey (usually another protozoan, such as Paramecium), the predator discharges numerous small paralyzing darts from its snout. Didinium then attaches to the Paramecium and devours it, everting like a hollow sphere to engulf a cell almost as large as itself. Much of this complex behavior—swimming, paralyzing, and consuming prey—is driven by cytoskeletal structures underlying the plasma membrane. This cortical layer includes, for example, parallel bundles of microtubules that form the core of each cilium and enable ciliary beating.

Figure 1-26. A assortment of protozoa demonstrating the immense diversity of this class of unicellular organisms. The drawings are at various magnifications, but a 10 µm scale bar is provided for each organism. Organisms A, B, D, E, and I belong to Ciliates, C to euglenids, G to amoebae, F to flagellates, and H to heliozoans. (From M. A. Sleigh, The Biology of Protozoa. London: Edward Arnold, 1973.)

The predatory behavior of Didinium, along with the properties that make it possible—its large size, capacity for phagocytosis, and ability to actively pursue prey—are exclusive to eukaryotes. It is highly probable that these traits arose very early in eukaryotic evolution, and that this capability is precisely what enabled eukaryotes to engulf bacteria and "domesticate" them as mitochondria and chloroplasts.

1.2.11. Genes Can Be Turned On and Off

It is worth noting that despite all The complexity of their organization, protists are far from being the pinnacle of eukaryotic evolution. More impressive evolutionary achievements were attained not by concentrating every conceivable complexity within a single cell, but by dividing responsibilities among various cell types. Evolution gave rise to multicellular organisms whose cells, despite sharing a common origin, undergo differentiation, becoming specialized to perform specific functions and forming corresponding Organs.

Fig. 1-27. This scanning electron micrograph shows one protist engulfing another. Protists are single-celled organisms characterized by a striking diversity of forms and behaviors. The ciliated protozoan Didinium (left) features two rings of motile cilia and a snout-like anterior protrusion used to capture prey. On the right, Didinium is shown swallowing another protist, Paramecium. (Courtesy of D. Barlow.)

Different specialized cell types within the same higher plant or animal often look completely different (Scheme 1-1). This seems paradoxical, since all cells of a multicellular organism are descendants of a single progenitor cell—namely, the fertilized egg. A common origin implies identical or similar genes. How, then, do these differences arise? In rare cases, cells lose a portion of their genetic material during specialization; an extreme example is mammalian erythrocytes, which lose their nucleus during differentiation. However, the vast majority of cells in almost all PLANT AND ANIMAL species retain the entire Genetic information contained in the fertilized egg. Specialization is driven not by the loss or acquisition of genes, but by changes in their expression.

Even bacteria do not constantly synthesize all possible types of proteins and are capable of regulating their internal processes in response to environmental conditions. For example, proteins required for the uptake and metabolism of lactose are produced by certain bacteria only when this sugar is present in the medium as the sole carbohydrate source. Other bacteria, when placed in adverse conditions, halt most normal metabolic processes and form spores with a tough, impermeable outer wall and a modified cytoplasmic composition.

Eukaryotic cells have evolved much more complex mechanisms of Gene Expression control that involve entire systems of interacting gene products. Both external and internal signals activate or suppress groups of cells. During Cell Differentiation, coordinated changes must occur in the membrane composition, the cytoskeleton, secreted products, and even metabolism. Compare, for example, a Skeletal Muscle cell adapted for contraction with an osteoblast—which secretes the hard bone matrix—within the same animal (Scheme 1-2). Such radical differences in cell type are driven by stable changes in gene expression. The mechanisms controlling these changes have evolved in eukaryotes to a degree unprecedented in prokaryotes.

1.2.12. Eukaryotic cells contain significantly more DNA than is necessary for protein coding

Eukaryotic cells contain an enormous amount of DNA. As we have already noted, human cells contain nearly 1,000 times more DNA than a typical bacterial cell, and the cells of some amphibians contain 10 times more than human cells (Fig. 1-28). However, apparently only a small fraction of this DNA (perhaps about 1% in human cells) actually codes for proteins. What, then, is the purpose of the remaining 99% of the DNA? One hypothesis is that it simply serves to increase the mass of the nucleus. According to another hypothesis, this DNA is a collection of cellular junk—sequences that have accumulated over centuries by co-opting the cell's synthetic machinery for their own Replication. Indeed, the DNA of many species harbors so-called mobile elements (Transposons)—sequences capable of abruptly "jumping" from one site in the DNA to another and even inserting additional copies of themselves into new locations. Mobile elements can thus multiply, much like a slowly spreading infection, making up an ever-increasing fraction of the genetic material.

Scheme 1-2. Some vertebrate cell types.

Fig. 1-28. Comparison of newt, human, and fruit fly chromosomes shown at the same scale. Judging by total chromosome size, a human cell contains more DNA than a fruit fly, but less than a newt. Some plants, such as the lily, contain more DNA than certain animals. (Based on H. S. Macgregor, Philos. Trans. R. Soc. Lond. [Biol.], 283: 309–318, 1978.)

However, evolution makes use of every opportunity. Regardless of the origin of noncoding DNA, it almost certainly performs some important function today. For example, part of this DNA plays a structural role, allowing the genetic material to condense or "package" in a specific manner. Another portion of this "excess" DNA is regulatory, participating in the turning on and off of genes that direct protein synthesis, and thus playing a pivotal role in the complex mechanisms of gene expression regulation in The Eukaryotic Cell.

1.2.13. The genetic material of eukaryotic cells is packaged in a highly complex manner

Eukaryotic DNA is so exceptionally long that the risk of tangling or breakage is very high. This is likely why Histones evolved—proteins characteristic of eukaryotes that bind to DNA and coil it into compact chromosomes that are much more manageable for various cellular processes (Fig. 1-29). Chromosome compaction is an essential part of preparing eukaryotic cells for division (Fig. 1-30). The DNA of all eukaryotes (with one minor exception) is associated with histones. The exceptionally vital importance of these proteins is demonstrated by the fact that they are remarkably evolutionarily conserved: some pea histones are identical (down to the amino acid) to their bovine counterparts.

In eukaryotic cells, numerous proteins other than histones are associated with DNA. Some of these influence the ability of DNA to interact with diverse molecules, thereby altering the set of expressed genes that distinguishes one specialized cell type from another.

Fig. 1-29. Diagram illustrating how positively charged proteins called histones facilitate the coiling of DNA into chromosomes.

Fig. 1-30. Schematic representation of a eukaryotic cell in mitosis. Left: an animal cell; right: a plant cell. The nuclear envelope has broken down, and the replicated DNA has condensed into two complete sets of chromosomes. The mitotic spindle, composed primarily of microtubules, distributes one set of chromosomes to each of the newly forming cells.

The membranes surrounding the nuclei of eukaryotic cells protect the delicate machinery of DNA control from many of the chemical changes occurring in the cytoplasm. Furthermore, they allow for the spatial Separation of two key stages of gene expression: 1) the synthesis of RNA from a DNA template (DNA Transcription), and 2) the utilization of these RNA sequences to synthesize specific proteins (RNA Translation). Prokaryotic cells lack this compartmentalization; in them, RNA translation into protein occurs concurrently with RNA transcription, beginning even before RNA synthesis is complete. In eukaryotes, by contrast (with the exception of mitochondria and chloroplasts, which in this respect, as in others, are closer to bacteria), these steps in the pathway from gene to protein are strictly segregated: transcription takes place in the nucleus, while translation occurs in the cytoplasm. Before RNA can participate in protein synthesis, it must exit the nucleus. To achieve this while still in the nucleus, the RNA undergoes complex processing (maturation), during which certain PARTS OF THE RNA molecule are removed while others are modified.

The structural complexity of The Genome in eukaryotic cells gives rise to much more sophisticated and diverse regulatory mechanisms than those found in bacterial cells.

Conclusion

All living cells are currently divided into two types: prokaryotic (bacteria and their close relatives) and eukaryotic. The former are believed to share general similarities with the earliest ancestral cells. Despite their relatively simple structure, prokaryotic cells exhibit remarkable biochemical diversity; for instance, bacteria display all Major Metabolic Pathways, including the three primary energy-yielding processes—glycolysis, respiration, and photosynthesis. Eukaryotic cells are larger and more complexly organized than prokaryotic cells. They contain more DNA and a variety of components required to support its complex functions. Eukaryotic DNA is housed within a membrane-enclosed nucleus, and the cytoplasm contains numerous other membrane-bound organelles. These include mitochondria, which carry out the final oxidation of nutrient molecules, and (in plant cells) chloroplasts, which are the site of photosynthesis. A wealth of evidence indicates that mitochondria and chloroplasts originated from early prokaryotic cells that became endosymbionts within a larger anaerobic cell. Another distinguishing feature of eukaryotic cells is the presence of a protein-filament cytoskeleton that organizes the cytoplasm and provides the machinery for cell movement.