Cells are divided into two main classes, initially defined by whether they contain a nucleus. Prokaryotic cells (bacteria) lack a nuclear envelope; eukaryotic cells have a nucleus in which the genetic material is separated from the cytoplasm. Prokaryotic cells are generally smaller and simpler than eukaryotic cells; in addition to the absence of a nucleus, their genomes are less complex and they do not contain cytoplasmic organelles or a cytoskeleton (Table 1.1). In spite of these differences, the same basic molecular mechanisms govern the lives of both prokaryotes and eukaryotes, indicating that all present-day cells are descended from a single primordial ancestor. How did this first cell develop? And how did the complexity and diversity exhibited by present-day cells evolve?
It appears that life first emerged at least 3.8 billion years ago, approximately 750 million years after Earth was formed (Figure 1.1). How life originated and how the first cell came into being are matters of speculation, since these events cannot be reproduced in the laboratory. Nonetheless, several types of experiments provide important evidence bearing on some steps of the process.
It was first suggested in the 1920s that simple organic molecules could form and spontaneously polymerize into macromolecules under the conditions thought to exist in primitive Earth’s atmosphere. At the time life arose, the atmosphere of Earth is thought to have contained little or no free oxygen, instead consisting principally of CO2 and N2 in addition to smaller amounts of gases such as H2, H2S, and CO. Such an atmosphere provides reducing conditions in which organic molecules, given a source of energy such as sunlight or electrical discharge, can form spontaneously. The spontaneous formation of organic molecules was first demonstrated experimentally in the 1950s, when Stanley Miller (then a graduate student) showed that the discharge of electric sparks into a mixture of H2, CH4, and NH3, in the presence of water, led to the formation of a variety of organic molecules, including several amino acids (Figure 1.2). Although Miller’s experiments did not precisely reproduce the conditions of primitive Earth, they clearly demonstrated the plausibility of the spontaneous synthesis of organic molecules, providing the basic materials from which the first living organisms arose.
The next step in evolution was the formation of macromolecules. The monomeric building blocks of macromolecules have been demonstrated to polymerize spontaneously under plausible prebiotic conditions. Heating dry mixtures of amino acids, for example, results in their polymerization to form polypeptides. But the critical characteristic of the macromolecule from which life evolved must have been the ability to replicate itself. Only a macromolecule capable of directing the synthesis of new copies of itself would have been capable of reproduction and further evolution.
Of the two major classes of informational macromolecules in present-day cells (nucleic acids and proteins), only the nucleic acids are capable of directing their own self-replication. Nucleic acids can serve as templates for their own synthesis as a result of specific base pairing between complementary nucleotides (Figure 1.3). A critical step in understanding molecular evolution was thus reached in the early 1980s, when it was discovered in the laboratories of Sid Altman and Tom Cech that RNA is capable of catalyzing a number of chemical reactions, including the polymerization of nucleotides. RNA is thus uniquely able both to serve as a template for and to catalyze its own replication. Consequently, RNA is generally believed to have been the initial genetic system, and an early stage of chemical evolution is thought to have been based on self-replicating RNA molecules-a period of evolution known as the RNA world. Ordered interactions between RNA and amino acids then evolved into the present-day genetic code, and DNA eventually replaced RNA as the genetic material.
The first cell is presumed to have arisen by the enclosure of self-replicating RNA in a membrane composed of phospholipids (Figure 1.4). As discussed in detail in the next chapter, phospholipids are the basic components of all present-day biological membranes, including the plasma membranes of both prokaryotic and eukaryotic cells. The key characteristic of the phospholipids that form membranes is that they are amphipathic molecules, meaning that one portion of the molecule is soluble in water and another portion is not. Phospholipids have long, water-insoluble (hydrophobic) hydrocarbon chains joined to water-soluble (hydrophilic) head groups that contain phosphate. When placed in water, phospholipids spontaneously aggregate into a bilayer with their phosphate-containing head groups on the outside in contact with water and their hydrocarbon tails in the interior in contact with each other. Such a phospholipid bilayer forms a stable barrier between two aqueous compartments-for example, separating the interior of the cell from its external environment.
The enclosure of self-replicating RNA and associated molecules in a phospholipid membrane would thus have maintained them as a unit, capable of self-reproduction and further evolution. RNA-directed protein synthesis may already have evolved by this time, in which case the first cell would have consisted of self-replicating RNA and its encoded proteins.
Because cells originated in a sea of organic molecules, they were able to obtain food and energy directly from their environment. But such a situation is self-limiting, so cells needed to evolve their own mechanisms for generating energy and synthesizing the molecules necessary for their replication. The generation and controlled utilization of metabolic energy is central to all cell activities, and the principal pathways of energy metabolism (discussed in detail in Chapter 2) are highly conserved in present-day cells. All cells use adenosine 5′-triphosphate (ATP) as their source of metabolic energy to drive the synthesis of cell constituents and carry out other energy-requiring activities, such as movement (e.g., muscle contraction). The mechanisms used by cells for the generation of ATP are thought to have evolved in three stages, corresponding to the evolution of glycolysis, photosynthesis, and oxidative metabolism (Figure 1.5). The development of these metabolic pathways changed Earth’s atmosphere, thereby altering the course of further evolution.
In the initially anaerobic atmosphere of Earth, the first energy-generating reactions presumably involved the breakdown of organic molecules in the absence of oxygen. These reactions are likely to have been a form of present-day glycolysis-the anaerobic breakdown of glucose to lactic acid, with the net energy gain of two molecules of ATP. In addition to using ATP as their source of intracellular chemical energy, all present-day cells carry out glycolysis, consistent with the notion that these reactions arose very early in evolution.
Glycolysis provided a mechanism by which the energy in preformed organic molecules (e.g., glucose) could be converted to ATP, which could then be used as a source of energy to drive other metabolic reactions. The development of photosynthesis is generally thought to have been the next major evolutionary step, which allowed the cell to harness energy from sunlight and provided independence from the utilization of preformed organic molecules. The first photosynthetic bacteria, which evolved more than 3 billion years ago, probably utilized H2S to convert CO2 to organic molecules-a pathway of photosynthesis still used by some bacteria. The use of H2O as a donor of electrons and hydrogen for the conversion of CO2 to organic compounds evolved later and had the important consequence of changing Earth’s atmosphere. The use of H2O in photosynthetic reactions produces the by-product free O2; this mechanism is thought to have been responsible for making O2 abundant in Earth’s atmosphere.
The release of O2 as a consequence of photosynthesis changed the environment in which cells evolved and is commonly thought to have led to the development of oxidative metabolism. Alternatively, oxidative metabolism may have evolved before photosynthesis, with the increase in atmospheric O2 then providing a strong selective advantage for organisms capable of using O2 in energy-producing reactions. In either case, O2 is a highly reactive molecule, and oxidative metabolism, utilizing this reactivity, has provided a mechanism for generating energy from organic molecules that is much more efficient than anaerobic glycolysis. For example, the complete oxidative breakdown of glucose to CO2 and H2O yields energy equivalent to that of 36 to 38 molecules of ATP, in contrast to the 2 ATP molecules formed by anaerobic glycolysis. With few exceptions, present-day cells use oxidative reactions as their principal source of energy.
Present-day prokaryotes, which include all the various types of bacteria, are divided into two groups-the archaebacteria and the eubacteria-which diverged early in evolution. Some archaebacteria live in extreme environments, which are unusual today but may have been prevalent in primitive Earth. For example, thermoacidophiles live in hot sulfur springs with temperatures as high as 80°C and pH values as low as 2. The eubacteria include the common forms of present-day bacteria-a large group of organisms that live in a wide range of environments, including soil, water, and other organisms (e.g., human pathogens).
Most bacterial cells are spherical, rod-shaped, or spiral, with diameters of 1 to 10 μm. Their DNA contents range from about 0.6 million to 5 million base pairs, an amount sufficient to encode about 5000 different proteins. The largest and most complex prokaryotes are the cyanobacteria, bacteria in which photosynthesis evolved.
The structure of a typical prokaryotic cell is illustrated by Escherichia coli (E. coli), a common inhabitant of the human intestinal tract (Figure 1.6). The cell is rod-shaped, about 1 μm in diameter and about 2 μm long. Like most other prokaryotes, E. coli is surrounded by a rigid cell wall composed of polysaccharides and peptides. Within the cell wall is the plasma membrane, which is a bilayer of phospholipids and associated proteins. Whereas the cell wall is porous and readily penetrated by a variety of molecules, the plasma membrane provides the functional separation between the inside of the cell and its external environment. The DNA of E. coli is a single circular molecule in the nucleoid, which, in contrast to the nucleus of eukaryotes, is not surrounded by a membrane separating it from the cytoplasm. The cytoplasm contains approximately 30,000 ribosomes (the sites of protein synthesis), which account for its granular appearance.
Like prokaryotic cells, all eukaryotic cells are surrounded by plasma membranes and contain ribosomes. However, eukaryotic cells are much more complex and contain a nucleus, a variety of cytoplasmic organelles, and a cytoskeleton (Figure 1.7). The largest and most prominent organelle of eukaryotic cells is the nucleus, with a diameter of approximately 5 μm. The nucleus contains the genetic information of the cell, which in eukaryotes is organized as linear rather than circular DNA molecules. The nucleus is the site of DNA replication and of RNA synthesis; the translation of RNA into proteins takes place on ribosomes in the cytoplasm.
In addition to a nucleus, eukaryotic cells contain a variety of membrane-enclosed organelles within their cytoplasm. These organelles provide compartments in which different metabolic activities are localized. Eukaryotic cells are generally much larger than prokaryotic cells, frequently having a cell volume at least a thousandfold greater. The compartmentalization provided by cytoplasmic organelles is what allows eukaryotic cells to function efficiently. Two of these organelles, mitochondria and chloroplasts, play critical roles in energy metabolism. Mitochondria, which are found in almost all eukaryotic cells, are the sites of oxidative metabolism and are thus responsible for generating most of the ATP derived from the breakdown of organic molecules. Chloroplasts are the sites of photosynthesis and are found only in the cells of plants and green algae. Lysosomes and peroxisomes also provide specialized metabolic compartments for the digestion of macromolecules and for various oxidative reactions, respectively. In addition, most plant cells contain large vacuoles that perform a variety of functions, including the digestion of macromolecules and the storage of both waste products and nutrients.
Because of the size and complexity of eukaryotic cells, the transport of proteins to their correct destinations within the cell is a formidable task. Two cytoplasmic organelles, the endoplasmic reticulum and the Golgi apparatus, are specifically devoted to the sorting and transport of proteins destined for secretion, incorporation into the plasma membrane, and incorporation into lysosomes. The endoplasmic reticulum is an extensive network of intracellular membranes, extending from the nuclear membrane throughout the cytoplasm. It functions not only in the processing and transport of proteins, but also in the synthesis of lipids. From the endoplasmic reticulum, proteins are transported within small membrane vesicles to the Golgi apparatus, where they are further processed and sorted for transport to their final destinations. In addition to this role in protein transport, the Golgi apparatus serves as a site of lipid synthesis and (in plant cells) as the site of synthesis of some of the polysaccharides that compose the cell wall.
Eukaryotic cells have another level of internal organization: the cytoskeleton, a network of protein filaments extending throughout the cytoplasm. The cytoskeleton provides the structural framework of the cell, determining cell shape and the general organization of the cytoplasm. In addition, the cytoskeleton is responsible for the movements of entire cells (e.g., the contraction of muscle cells) and for the intracellular transport and positioning of organelles and other structures, including the movements of chromosomes during cell division.
The eukaryotes developed at least 2.7 billion years ago, following some 1 to 1.5 billion years of prokaryotic evolution. Studies of their DNA sequences indicate that the archaebacteria and eubacteria are as different from each other as either is from present-day eukaryotes. Therefore, a very early event in evolution appears to have been the divergence of three lines of descent from a common ancestor, giving rise to present-day archaebacteria, eubacteria, and eukaryotes. Interestingly, many archaebacterial genes are more similar to those of eukaryotes than to those of eubacteria, indicating that the archaebacteria and eukaryotes share a common line of evolutionary descent and are more closely related to each other than either is to the eubacteria (Figure 1.8).
A critical step in the evolution of eukaryotic cells was the acquisition of membrane-enclosed subcellular organelles, allowing the development of the complexity characteristic of these cells. The organelles are thought to have been acquired as a result of the association of prokaryotic cells with the ancestor of eukaryotes.
The hypothesis that eukaryotic cells evolved from a symbiotic association of prokaryotes-endosymbiosis-is particularly well supported by studies of mitochondria and chloroplasts, which are thought to have evolved from bacteria living in large cells. Both mitochondria and chloroplasts are similar to bacteria in size, and like bacteria, they reproduce by dividing in two. Most important, both mitochondria and chloroplasts contain their own DNA, which encodes some of their components. The mitochondrial and chloroplast DNAs are replicated each time the organelle divides, and the genes they encode are transcribed within the organelle and translated on organelle ribosomes. Mitochondria and chloroplasts thus contain their own genetic systems, which are distinct from the nuclear genome of the cell. Furthermore, the ribosomes and ribosomal RNAs of these organelles are more closely related to those of bacteria than to those encoded by the nuclear genomes of eukaryotes.
An endosymbiotic origin for these organelles is now generally accepted, with mitochondria thought to have evolved from aerobic bacteria and chloroplasts from photosynthetic bacteria, such as the cyanobacteria. The acquisition of aerobic bacteria would have provided an anaerobic cell with the ability to carry out oxidative metabolism. The acquisition of photosynthetic bacteria would have provided the nutritional independence afforded by the ability to perform photosynthesis. Thus, these endosymbiotic associations were highly advantageous to their partners and were selected for in the course of evolution. Through time, most of the genes originally present in these bacteria apparently became incorporated into the nuclear genome of the cell, so only a few components of mitochondria and chloroplasts are still encoded by the organelle genomes.
Many eukaryotes are unicellular organisms that, like bacteria, consist of only single cells capable of self-replication. The simplest eukaryotes are the yeasts. Yeasts are more complex than bacteria, but much smaller and simpler than the cells of animals or plants. For example, the commonly studied yeast Saccharomyces cerevisiae is about 6 μm in diameter and contains 12 million base pairs of DNA (Figure 1.9). Other unicellular eukaryotes, however, are far more complex cells, some containing as much DNA as human cells have (Table 1.2). They include organisms specialized to perform a variety of tasks, including photosynthesis, movement, and the capture and ingestion of other organisms as food. Amoeba proteus, for example, is a large, complex cell. Its volume is more than 100,000 times that of E. coli, and its length can exceed 1 mm when the cell is fully extended (Figure 1.10). Amoebas are highly mobile organisms that use cytoplasmic extensions, called pseudopodia, to move and to engulf other organisms, including bacteria and yeasts, as food. Other unicellular eukaryotes (the green algae) contain chloroplasts and are able to carry out photosynthesis.
Multicellular organisms evolved from unicellular eukaryotes at least 1.7 billion years ago. Some unicellular eukaryotes form multicellular aggregates that appear to represent an evolutionary transition from single cells to multicellular organisms. For instance, the cells of many algae (e.g., the green alga Volvox) associate with each other to form multicellular colonies (Figure 1.11), which are thought to have been the evolutionary precursors of present-day plants. Increasing cell specialization then led to the transition from colonial aggregates to truly multicellular organisms. Continuing cell specialization and division of labor among the cells of an organism have led to the complexity and diversity observed in the many types of cells that make up present-day plants and animals, including human beings.
Plants are composed of fewer cell types than are animals, but each different kind of plant cell is specialized to perform specific tasks required by the organism as a whole (Figure 1.12). The cells of plants are organized into three main tissue systems: ground tissue, dermal tissue, and vascular tissue. The ground tissue contains parenchyma cells, which carry out most of the metabolic reactions of the plant, including photosynthesis. Ground tissue also contains two specialized cell types (collenchyma cells and sclerenchyma cells) that are characterized by thick cell walls and provide structural support to the plant. Dermal tissue covers the surface of the plant and is composed of epidermal cells, which form a protective coat and allow the absorption of nutrients. Finally, several types of elongated cells form the vascular system (the xylem and phloem), which is responsible for the transport of water and nutrients throughout the plant.
The cells found in animals are considerably more diverse than those of plants. The human body, for example, is composed of more than 200 different kinds of cells, which are generally considered to be components of five main types of tissues: epithelial tissue, connective tissue, blood, nervous tissue, and muscle (Figure 1.13). Epithelial cells form sheets that cover the surface of the body and line the internal organs. There are many different types of epithelial cells, each specialized for a specific function, including protection (the skin), absorption (e.g., the cells lining the small intestine), and secretion (e.g., cells of the salivary gland). Connective tissues include bone, cartilage, and adipose tissue, each of which is formed by different types of cells (osteoblasts, chondrocytes, and adipocytes, respectively). The loose connective tissue that underlies epithelial layers and fills the spaces between organs and tissues in the body is formed by another cell type, the fibroblast. Blood contains several different types of cells, which function in oxygen transport (red blood cells, or erythrocytes), inflammatory reactions (granulocytes, monocytes, and macrophages), and the immune response (lymphocytes). Nervous tissue is composed of nerve cells, or neurons, which are highly specialized to transmit signals throughout the body. Various types of sensory cells, such as cells of the eye and ear, are further specialized to receive external signals from the environment. Finally, several different types of muscle cells are responsible for the production of force and movement.
The evolution of animals clearly involved the development of considerable diversity and specialization at the cellular level. Understanding the mechanisms that control the growth and differentiation of such a complex array of specialized cells, starting from a single fertilized egg, is one of the major challenges facing contemporary cell and molecular biology