All Cells Translate RNA into Protein in the Same Way

The translation of genetic information from the 4-letter alphabet of

polynucleotides into the 20-letter alphabet of proteins is a complex process.

The rules of this translation seem in some respects neat and rational, in other

respects strangely arbitrary, given that they are (with minor exceptions)

identical in all living things. These arbitrary features, it is thought, reflect

frozen accidents in the early history of life chance properties of the earliest

organisms that were passed on by heredity and have become so deeply

embedded in the constitution of all living cells that they cannot be changed

without wrecking cell organization.

The information in the sequence of a messenger RNA molecule is read out in

groups of three nucleotides at a time: each triplet of nucleotides, or

specifies (codes for) a single amino acid in a corresponding protein. Since

there are 64 (= 4 × 4 × 4) possible codons, but only 20 amino acids, there are

necessarily many cases in which several codons correspond to the same amino

acid. The code is read out by a special class of small RNA molecules, the

transfer RNAs (

specific amino acid, and displays at its other end a specific sequence of three

nucleotides an

a particular codon or subset of codons in mRNA (Figure 1-9).

For synthesis of protein, a succession of tRNA molecules charged with their

appropriate amino acids have to be brought together with an mRNA molecule

and matched up by base-pairing through their anticodons with each of its

successive codons. The amino acids then have to be linked together to extend

the growing protein chain, and the tRNAs, relieved of their burdens, have to be

released. This whole complex of processes is carried out by a giant

multimolecular machine, the ribosome, formed of two main chains of RNA,

called ribosomal RNAs (

evolutionarily ancient molecular juggernaut latches onto the end of an mRNA

molecule and then trundles along it, capturing loaded tRNA molecules and

stitching together the amino acids they carry to form a new protein chain

(Figure 1-rRNAs), and more than 50 different proteins. Thiscodon,tRNAs). Each type of tRNA becomes attached at one end to aanticodon that enables it to recognize, through basepairing,

All Cells Store Their Hereditary Information in the Same Linear Chemical Code (DNA)

Computers have made us familiar with the concept of information as a

measurable quantity a million bytes (corresponding to about 200 pages of

text) on a floppy disk, 600 million on a CD-ROM, and so on. They have also

made us uncomfortably aware that the same information can be recorded in

many different physical forms. A document that is written on one type of

computer may be unreadable on another. As the computer world has evolved,

the discs and tapes that we used 10 years ago for our electronic archives have

become unreadable on present-day machines. Living cells, like computers,

deal in information, and it is estimated that they have been evolving and

diversifying for over 3.5 billion years. It is scarcely to be expected that they

should all store their information in the same form, or that the archives of one

type of cell should be readable by the information-handling machinery of

another. And yet it is so. All living cells on Earth, without any known

exception, store their hereditary information in the form of double-stranded

molecules of DNA long unbranched paired polymer chains, formed always

of the same four types of monomers A, T, C, G. These monomers are strung

together in a long linear sequence that encodes the genetic information, just as

the sequence of 1s and 0s encodes the information in a computer file. We can

take a piece of DNA from a human cell and insert it into a bacterium, or a

piece of bacterial DNA and insert it into a human cell, and the information will

be successfully read, interpreted, and copied. Using chemical methods,

scientists can read out the complete sequence of monomers in any DNA

molecule extending for millions of nucleotides and thereby decipher the

hereditary information that each organism contains.

All Cells Replicate Their Hereditary Information byTemplated Polymerization

which this information is copied throughout the living world.

To understand the mechanisms that make life possible, one must understand

the structure of the double-stranded DNA molecule. Each monomer in a single

DNA strand that is, each nucleotide consists of two parts: a sugar

(deoxyribose) with a phosphate group attached to it, and a

either adenine (A), guanine (G), cytosine (C) or thymine (T) (Figure 1-2). Each

sugar is linked to the next via the phosphate group, creating a polymer chain

composed of a repetitive sugar-phosphate backbone with a series of bases

protruding from it. The DNA polymer is extended by adding monomers at one

end. For a single isolated strand, these can, in principle, be added in any order,

because each one links to the next in the same way, through the part of the

molecule that is the same for all of them. In the living cell, however, there is a

constraint: DNA is not synthesized as a free strand in isolation, but on a

template formed by a preexisting DNA strand. The bases protruding from the

existing strand bind to bases of the strand being synthesized, according to a

strict rule defined by the complementary structures of the bases: A binds to T,
DNA replicationtemplated polymerization is the way in which this information is copied throughout the living world.

and C binds to G. This base-pairing holds fresh monomers in place and thereby

controls the selection of which one of the four monomers shall be added to the

growing strand next. In this way, a double-stranded structure is created,

consisting of two exactly complementary sequences of As, Cs, Ts, and Gs. The

two strands twist around each other, forming a double helix (Figure 1-2E).

The bonds between the base pairs are weak compared with the sugarphosphate

links, and this allows the two DNA strands to be pulled apart

without breakage of their backbones. Each strand then can serve as a template,

in the way just described, for the synthesis of a fresh DNA strand

complementary to itself a fresh copy, that is, of the hereditary information

(Figure 1-3). In different types of cells, this process of

occurs at different rates, with different controls to start it or stop it, and

different auxiliary molecules to help it along. But the basics are universal:

DNA is the information store, and which this information is copied throughout the living world

The Fragment of Genetic Information Corresponding to One Protein Is One Gene

DNA molecules as a rule are very large, containing the specifications for

thousands of proteins. Segments of the entire DNA sequence are therefore

transcribed into separate mRNA molecules, with each segment coding for a

different protein. A gene is defined as the segment of DNA sequence

corresponding to a single protein (or to a single catalytic or structural RNA

molecule for those genes that produce RNA but not protein).

In all cells, the

manufacturing its full repertoire of possible proteins at full tilt all the time, the

cell adjusts the rate of transcription and translation of different genes

independently, according to need. Stretches of

interspersed among the segments that code for protein, and these noncoding

regions bind to special protein molecules that control the local rate of

transcription (Figure 1-11). Other noncoding DNA is also present, some of it

serving, for example, as punctuation, defining where the information for an

individual protein begins and ends. The quantity and organization of the

regulatory and other noncoding DNA vary widely from one class of organisms

to another, but the basic strategy is universal. In this way, the genome of the

cell that is, the total of its genetic information as embodied in its complete

DNA sequence dictates not only the nature of the cell's proteins, but also

when and where they are to be made.

All Cells Transcribe Portions of Their Hereditary Information into the Same Intermediary Form (RNA)

To carry out its information-storage function, DNA must do more than copy

itself before each cell division by the mechanism just described. It must also

express its information, putting it to use so as to guide the synthesis of other

molecules in the cell. This also occurs by a mechanism that is the same in all

living organisms, leading first and foremost to the production of two other key

classes of polymers: RNAs and proteins. The process begins with a templated

polymerization called transcription, in which segments of the DNA sequence

are used as templates to guide the synthesis of shorter molecules of the closely

related polymer

of translation, many of these RNA molecules serve to direct the synthesis of

polymers of a radically different chemical class the

In RNA, the backbone is formed of a slightly different sugar from that of

DNA ribose instead of deoxyribose and one of the four bases is slightly

different uracil (U) in place of thymine (T); but the other three bases A, C,

and G are the same, and all four bases pair with their complementary

counterparts in DNA the A, U, C, and G of RNA with the T, A, G, and C of

DNA. During transcription, RNA monomers are lined up and selected for

polymerization on a template strand of DNA in the same way that DNA

monomers are selected during replication. The outcome is therefore a polymer

molecule whose sequence of nucleotides faithfully represents a part of the

cell's genetic information, even though written in a slightly different alphabet,

consisting of RNA monomers instead of DNA monomers.

The same segment of DNA can be used repeatedly to guide the synthesis of

many identical RNA transcripts. Thus, whereas the cell's archive of genetic

information in the form of DNA is fixed and sacrosanct, the RNA transcripts

are mass-produced and disposable (Figure 1-5). As we shall see, the primary

role of most of these transcripts is to serve as intermediates in the transfer of

genetic information: they serve as messenger RNA (

synthesis of proteins according to the genetic instructions stored in the DNA.

RNA molecules have distinctive structures that can also give them other

specialized chemical capabilities. Being single-stranded, their backbone is

flexible, so that the polymer chain can bend back on itself to allow one part of

the molecule to form weak bonds with another part of the same molecule. This

occurs when segments of the sequence are locally complementary: a ...

GGGG... segment, for example, will tend to associate with a ...CCCC...

segment. These types of internal associations can cause an RNA chain to fold

up into a specific shape that is dictated by its sequence (Figure 1-6). The shape

of the RNA molecule, in turn, may enable it to recognize other molecules by

binding to them selectively and even, in certain cases, to catalyze chemical

changes in the molecules that are bound. As we see later in this book, a few

chemical reactions catalyzed by RNA molecules are crucial for several of the

most ancient and fundamental processes in living cells, and it has been

suggested that more extensive catalysis by RNA played a central part in the

early evolution of life (discussed in Chapter 6).mRNA) to guide theribonucleic acid, or RNA. Later, in the more complex processproteins (Figure 1-4).

All Cells Use Proteins as Catalysts

Protein molecules, like DNA and RNA molecules, are long unbranched

polymer chains, formed by the stringing together of monomeric building

blocks drawn from a standard repertoire that is the same for all living cells.

Like DNA and RNA, they carry information in the form of a linear sequence

of symbols, in the same way as a human message written in an alphabetic

script. There are many different protein molecules in each cell, and leaving

out the water they form most of the cell's mass.

The monomers of protein, the amino acids, are quite different from those of

DNA and RNA, and there are 20 types, instead of 4. Each amino acid is built

around the same core structure through which it can be linked in a standard

way to any other amino acid in the set; attached to this core is a side group that

gives each amino acid a distinctive chemical character. Each of the protein

molecules, or polypeptides, created by joining amino acids in a particular

sequence folds into a precise three-dimensional form with reactive sites on its

surface (Figure 1-7A). These amino acid polymers thereby bind with high

specificity to other molecules and act as enzymes to catalyze reactions in

which covalent bonds are made and broken. In this way they direct the vast

majority of chemical processes in the cell (Figure 1-7B). Proteins have a host

of other functions as well maintaining structures, generating movements,

sensing signals, and so on each protein molecule performing a specific

function according to its own genetically specified sequence of amino acids.

Proteins, above all, are the molecules that put the cell's genetic information

into action.

Thus, polynucleotides specify the amino acid sequences of proteins. Proteins,

in turn, catalyze many chemical reactions, including those by which new DNA

molecules are synthesized, and the genetic information in DNA is used to

make both RNA and proteins. This feedback loop is the basis of the

autocatalytic, self-reproducing behavior of living organisms (Figure 1-

8).

All Cells Function as Biochemical Factories Dealing with the Same Basic Molecular Building Blocks

Because all cells make DNA, RNA, and protein, and these macromolecules are

composed of the same set of subunits in every case, all cells have to contain

and manipulate a similar collection of small molecules, including simple

sugars, nucleotides, and amino acids, as well as other substances that are

universally required for their synthesis. All cells, for example, require the

phosphorylated nucleotide

for the synthesis of DNA and RNA; and all cells also make and consume this

molecule as a carrier of free energy and phosphate groups to drive many other

chemical reactions.

Although all cells function as biochemical factories of a broadly similar type,

many of the details of their small-molecule transactions differ, and it is not as

easy as it is for the informational macromolecules to point out the features that

are strictly universal. Some organisms, such as plants, require only the

simplest of nutrients and harness the energy of sunlight to make from these

almost all their own small organic molecules; other organisms, such as

animals, feed on living things and obtain many of their organic molecules

ready-made. We return to this point below.ATP (adenosine triphosphate) as a building block

All Cells Are Enclosed in a Plasma Membrane Across Which Nutrients and Waste Materials Must Pass

There is, however, at least one other feature of cells that is universal: each one

is bounded by a membrane the plasma membrane. This container acts as a

selective barrier that enables the cell to concentrate nutrients gathered from its

environment and retain the products it synthesizes for its own use, while

excreting its waste products. Without a plasma membrane, the cell could not

maintain its integrity as a coordinated chemical system.

This membrane is formed of a set of molecules that have the simple physicochemical

property of being

hydrophobic (water-insoluble) and another part that is hydrophilic (watersoluble).

When such molecules are placed in water, they aggregate

spontaneously, arranging their hydrophobic portions to be as much in contact

with one another as possible to hide them from the water, while keeping their

hydrophilic portions exposed. Amphipathic molecules of appropriate shape,

such as the phospholipid molecules that comprise most of the plasma

membrane, spontaneously aggregate in water to form a

small closed vesicles (Figure 1-12). The phenomenon can be demonstrated in a

test tube by simply mixing phospholipids and water together; under

appropriate conditions, small vesicles form whose aqueous contents are

isolated from the external medium.

Although the chemical details vary, the hydrophobic tails of the predominant

membrane molecules in all cells are hydrocarbon polymers (-CH

and their spontaneous assembly into a bilayered vesicle is but one of many

examples of an important general principle: cells produce molecules whose

chemical properties cause them to

needs.

The boundary of the cell cannot be totally impermeable. If a cell is to grow and

reproduce, it must be able to import raw materials and export waste across its

plasma membrane. All cells therefore have specialized proteins embedded in

their membrane that serve to transport specific molecules from one side to the

other (Figure 1-13). Some of these

the proteins that catalyze the fundamental small-molecule reactions inside the

cell, have been so well preserved over the course of evolution that one can

recognize the family resemblances between them in comparisons of even the

most distantly related groups of living organisms.

The transport proteins in the membrane largely determine which molecules

enter the cell, and the catalytic proteins inside the cell determine the reactions

that those molecules undergo. Thus, by specifying the set of proteins that the

cell is to manufacture, the genetic information recorded in the DNA sequence

dictates the entire chemistry of the cell; and not only its chemistry, but also its

form and its behavior, for these too are chiefly constructed and controlled by

the cell's proteins.2-CH2-CH2-),self-assemble into the structures that a cellmembrane transport proteins, like some ofamphipathic that is, consisting of one part that isbilayer that creates

A Living Cell Can Exist with Fewer Than 500 Genes

The basic principles of biological information transfer are simple enough, but

how complex are real living cells? In particular, what are the minimum

requirements? We can get a rough indication by considering the species that

has the smallest known genome the bacterium

Mycoplasma genitalium

(Figure 1-14)

environment provides it with many of its small molecules ready-made.

Nevertheless, it still has to make all the large molecules DNA, RNAs, and

proteins required for the basic processes of heredity. It has only 477 genes in

its genome of 580,070 nucleotide pairs, representing 145,018 bytes of

information about as much as it takes to record the text of one chapter of this

book. Cell biology may be complicated, but it is not impossibly so.

The minimum number of genes for a viable cell in today's environments is

probably not less than 200 300. As we shall see in the next section, when we

compare the most widely separated branches of the tree of life, we find that a

core set of over 200 genes is common to them all.. This organism lives as a parasite in mammals, and its

Life Requires Free Energy

A living cell is a system far from chemical equilibrium: it has a large internal

free energy, meaning that if it is allowed to die and decay towards chemical

equilibrium, a great deal of energy is released to the environment as heat. For

the cell to make a new cell in its own image, it must take in free energy from

the environment, as well as raw materials, to drive the necessary synthetic

reactions. This consumption of free energy is fundamental to life. When it

stops, a cell dies. Genetic information is also fundamental to life. Is there any

connection?

The answer is yes: free energy is required for the propagation of information,

and there is, in fact, a precise quantitative relationship between the two

entities. To specify one bit of information that is, one yes/no choice between

two equally probable alternatives costs a defined amount of free energy

(measured in joules), depending on the temperature. The proof of this abstract

general principle of statistical thermodynamics is quite arduous, and depends

on the precise definition of the term "free energy" (discussed in Chapter 2).

The basic idea, however, is not difficult to understand intuitively in the context

of DNA synthesis.

To create a new DNA molecule with the same sequence as an existing DNA

molecule, nucleotide monomers must be lined up in the correct sequence on

the DNA strand that is used as the template. At each point in the sequence, the

selection of the appropriate nucleotide depends on the fact that the correctly

matched nucleotide binds to the template more strongly than mismatched

nucleotides. The greater the difference in binding energy, the rarer are the

occasions on which a mismatched nucleotide is accidentally inserted in the

sequence instead of the correct nucleotide. A high-fidelity match, whether it is

achieved through the direct and simple mechanism just outlined, or in a more

complex way, with the help of a set of auxiliary chemical reactions, requires

that a lot of free energy be released and dissipated as heat as each correct

nucleotide is slotted into its place in the structure. This cannot happen unless

the system of molecules carries a large store of free energy at the outset.

Eventually, after the newly recruited nucleotides have been joined together to

form a new DNA strand, a fresh input of free energy is required to force the

matched nucleotides apart again, since each new strand has to be separated

from its old template strand to allow the next round of replication.

The cell therefore requires free energy, which has to be imported somehow

from its surroundings, to replicate its genetic information faithfully. The same

principle applies to the synthesis of most of the molecules in cells. For

example, in the production of RNAs or proteins, the existing genetic

information dictates the sequence of the new molecule through a process of

molecular matching, and free energy is required to drive forward the many

chemical reactions that construct the monomers from raw materials and link

them together correctly.

Introduction to Nucleic Acid

It has been obvious for as long as humans have sown crops or raised animals that each seed or fertilized egg must contain a hidden plan, or design, for the development of the organism. In modern times the science of genetics grew up around the premise of invisible informationcontaining elements, called genes, that are distributed to each daughter cell when a cell divides.

Therefore, before dividing, a cell has to make a copy of its genes in order to give a complete set to each daughter cell. The genes in the sperm and egg cells carry the hereditary information from one generation to the next.

The inheritance of biological characteristics must involve patterns of atoms that follow the laws of physics and chemistry: in other words, genes must be formed from molecules. At first the nature of these molecules was hard to imagine. What kind of molecule could be stored in a cell and direct the activities of a developing organism and also be capable of accurate and almost unlimited replication?

By the end of the nineteenth century biologists had recognized that the carriers of inherited information were the chromosomes that become visible in the nucleus as a cell begins to divide. But the evidence that the deoxyribonucleic acid (DNA) in these chromosomes is the substance of which genes are made came only much later, from studies on bacteria. In 1944 it was shown that adding purified DNA from one strain of bacteria to a second, slightly different bacterial strain conferred heritable properties characteristic of the first strain upon the second. Because it had been commonly believed that only proteins have enough conformational complexity to carry genetic information, this discovery came as a surprise, and it was not generally accepted until the early 1950s. Today the idea that DNA carries genetic information in its long chain of nucleotides is so fundamental to biological thought that it is sometimes difficult to realize the enormous intellectual gap that it filled.

What is enzyme?

Enzymes:

The sensitivity of cellular constituents to environmental extremes places another constraint on the reactions of metabolism. The rate at which cellular reactions proceed is a very important factor in maintenance of the living state.

However, the common ways chemists accelerate reactions are not available to cells; the temperature cannot be raised, acid or base cannot be added, the pressure cannot be elevated, and concentrations cannot be dramatically increased. Instead, biomolecular catalysts mediate cellular reactions. These catalysts, called enzymes, accelerate the reaction rates many orders of magnitude and, by selecting the substances undergoing reaction, determine the specific reaction taking place. Virtually every metabolic reaction is served by an enzyme whose sole biological purpose is to catalyze its specific reaction.