Molecular biology of the cell (6 th edition)
1-41
The universal features of cells on Earth
Parent organisms hand down information specifying the characteristics that the offspring shall have.
This heredity distinguishes life from other processes. Organisms are made up from single cells or
multicellular cities with groups of cells that perform specialized functions, but even these
multicellular organism came from a single cell.
All cells store their hereditary information in the same linear chemical code: DNA
Living cells store information. All living cells on Earth store their hereditary information in the form of
double-stranded molecules of DNA, made from four types of monomers, with the nicknames A, T, C
and G. Using chemical methods, scientists have learned how to read out the complete sequence of
monomers in any DNA molecule and thereby decipher all the hereditary information in each
organism.
All cells replicate their hereditary information by templated polymerization
Each monomer of a single DNA strand (nucleotide) consists of a sugar with a phosphate group
attached and a base (adenine (A), guanine (G), cytosine (C) or thymine (T)). Each sugar is linked to the
next via the phosphate group. The DNA polymer is extended by adding monomers at one end. For a
single isolated strand, these monomers can be added in any order, however, DNA is not synthesized
as a free strand in isolation, but on a template formed by pre-existing DNA. The bases protruding
from the existing strand bind to bases of the strand being synthesized, according to the
complementary structure of the bases: A binds to T, and C binds to G. In this way, a double-stranded
structure is created, consisting of two exactly complementary sequences, that twist around each
other. The bonds between the base pairs are weak, allowing the strands to be pulled apart without
breakage of the backbones. Each strand then can serve as a template for the synthesis of a fresh DNA
strand. The rate, control and auxiliary molecules helping this DNA replication can alter from cell type
to cell type.
All cells transcribe portions of their hereditary information into the same intermediary form: RNA
DNA must also express its information, by letting the information guide the synthesis of other
molecules in the cell. This expression leads first and foremost to the production of RNAs and proteins.
The process begins with transcription, in which segments of the DNA are used as templates for the
synthesis of shorter molecules of RNA. Later, many RNA molecules are translated to proteins. In RNA,
the backbone is formed with ribose and uracil (U) replaces thymine (T), but the base pairs remain
(relatively) unaltered. During transcription, the RNA monomers are lined up and selected for
polymerization on a template strand of DNA. The outcome is a polymer whose sequence of
nucleotides represents a portion of the genetic information. The same segment of DNA can be used
repeatedly to guide the synthesis of many identical RNA molecules: RNA is mass-produced and
disposable. RNA molecules have distinctive structures that give them specialized chemical
capabilities. They have a flexible backbone, so the polymer can bend back on itself to allow one part
of the molecule to form weak bonds with another part of the same molecule. These types of internal
associations can cause RNA to fold up into a specific shape, dictated by the sequence. The shape of
the RNA may enable it to recognize other molecules by binding to them selectively and even to
catalyse chemical changes in the molecules that are bound.
All cells use proteins as catalysts
Protein molecules are long unbranched polymer chains, formed by stringing together amino acids.
They carry information in the form of a linear sequence of symbols. There are 20 amino acids, 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 the amino acid a distinctive chemical
character. Each protein is a polypeptide created by joining amino acids in a particular sequence. By
folding in a precise three-dimensional form with reactive sites on its surface, proteins can bind with
high specificity to other molecules and can act as enzymes to catalyse reactions, but they have other
functions as well, according to its own sequence.
All cells translate RNA into protein in the same way
The translation of genetic information from DNA to protein is a complex process, but it is identical in
all living things. It turns out that the information in the mRNA sequence is read out in groups of three
nucleotides at a time; each triplet of nucleotides (codon) codes for a single amino acid in the
corresponding protein. There are 23=64 possible codons, all of which occur, so several codons can
correspond to the same amino acid. This genetic code is read out by transfer RNAs (tRNAs). Each type
of tRNA becomes attached at one end to a specific amino acid, and displays at its other end an
anticodon, enabling it to recognize a codon through base-pairing. This occurs on the ribosome, a large
multimolecular machine composed of protein and rRNA.
Each protein is encoded by a specific gene
Special sequences in the DNA define where the information for each protein begins and ends.
Individual segments of DNA are transcribed into separate mRNA molecules, coding for different
proteins. Each such DNA segment represents one gene. The mRNA from one gene can be processed
in more than one way, fiving rise to a set of alternative versions of proteins. In addition, some RNAs
are not translated, but have a function in themselves. The expression of individual genes is regulated;
the cell adjusts the rate of transcription and translation of different genes independently, according to
the need. Regulatory DNA sequences are interspersed among the segments that code for protein,
and can bind to special protein molecules that control the local rate of transcription.
Life requires free energy
A living cell operates far from chemical equilibrium. For a cell to grow or to make new cells in its
image, it must take in free energy as well as raw materials. The consumption of free energy is
fundamental to life. Free energy is also required for the propagation of genetic information. All
molecules in the cell have thermal energy, moving around violently at random. To make ordered
structures, these molecules must be captured, arranged and linked together with bonds that are
strong enough to resist the disordering effect of thermal motion. This process needs free energy.
All cells function as biochemical factories dealing with the same basic molecular building blocks
All cells have to contain and manipulate a similar collection of small molecules (sugars, nucleotides,
and amino acids). All cells require free energy carriers like ATP to drive a huge number of chemical
reactions in the cell. Between cells, many details of the small-molecule transactions differ: plants
produce organic molecules from the energy of sunlight, while animals must obtain many of their
organic molecules ready-made.
All cells are enclosed in a plasma membrane across which nutrients and waste materials must pass
Each cell is enclosed by the plasma membrane, acting as a selective barrier that enables the cell to
concentrate nutrients from the environment and retain the products synthesizes for its own use,
while excreting its waste products. The membrane molecules are amphiphilic: they consist of a
hydrophobic and a hydrophilic part. The hydrophobic portions will be close together when these
molecules are put in water: the phospholipids that form the cell membrane thusly form a self-
assembled bilayer, with their hydrocarbon tails between the two layers. The cell boundary is not
totally impermeable. Within it are membrane transport proteins that can transport specific molecules
across the membrane.
,A living cell can exist with fewer than 500 genes
The minimum number of genes for a viable cell in today’s environments is probably about 300.
The diversity of genomes and the tree of life
Living things can be found everywhere on Earth, even in the most extreme parts. This is due to the
fact that they are adapted to live under these circumstances.
Cells can be powered by a variety of free-energy sources
Living organisms get their free energy from other living things or the organic chemicals they produces
(organotrophic). Others derive their energy from sunlight (phototrophic), or even from energy-rich
systems of inorganic chemicals (lithotrophic). Phototrophic organisms mainly include many types of
bacteria, algae and plants. They produce oxygen in the process. Lithotrophic organisms are
microscopic and live in extreme parts of the world. Some get energy from aerobic reactions, some
from anaerobic. By doing so, a whole ecosystem can form where there is no light.
Some cells fix nitrogen and carbon dioxide for others
A large amount of free energy is needed to drive the reactions that use N 2 and CO2 to make the
organic compounds needed for further biosynthesis. Many types of living cells lack the machinery to
achieve this fixation. Animals depend on plants for our supplies of organic carbon and nitrogen
compounds. Plants can fix carbon dioxide, but depend on nitrogen-fixing bacteria to supply their
need for nitrogen compounds.
The greatest biochemical diversity lives among prokaryotic cells
Eukaryotes keep their DNA in a nucleus. Prokaryotes have no distinct nuclear compartment to house
their DNA. Most prokaryotic cells are small and simple. They often have a cell wall, beneath which a
plasma membrane encloses a single cytoplasmic compartment containing all molecules needed for
life. They can live in an enormous variety of ecological niches, and can be organotrophic,
phototrophic or lithotrophic.
The tree of life has three primary branches: bacteria, archaea, and eukaryotes
The classification of living things has traditionally depended on comparisons of their outward
appearances, but when disparities between organisms become very great, these methods fail.
Genome analysis has given us a simpler, more direct, and much more powerful way to determine
evolutionary relationships: the DNA sequences can just be compared by computers. This approach
has shown that the prokaryotes consist of two groups: bacteria and archaea. Genome analyses have
revealed that the first eukaryotic cell formed after a particular type of archaeal cell engulfed an
bacterium.
Some genes evolve rapidly; others are highly conserved
Both in the storage and in the copying of genetic information, mutation occur: the daughter cells
after cell division are not quite identical to each other and the parent. On rare occasions, the error
may represent a change for the better, but mostly it has no effect or cause serious damage.
Favourable mutations are kept, while unfavourable mutations mostly die out. Through endless
repetition of this cycle of trial and error organisms evolve. Some parts of the genome will change
more easily than others. A segment of DNA that does not code for protein and has no significant
regulatory role is free to change, but a gene that codes for an essential protein or RNA molecule
cannot alter easily: the cell in which this mistake occurs, will be eliminated. These genes can be used
to examine family relationships between organisms.
Most bacteria and archaea have 1000-6000 genes
Most prokaryotes carry only the essentials: their genomes are small, with genes packed closely
together and minimal quantities of regulatory DNA between them, making it easy to sequence the
, complete DNA. This complete sequence reveals the genes an organisms possesses and the genes it
lacks.
New genes are generated from pre-existing genes
No gene is entirely new, but innovation can occur in several ways, such as intragenic mutation, in
which an existing gene can be randomly modified by errors that occur in DNA replication, or gene
duplication, in which an existing gene is accidentally duplicated and one of them diverges in the
course of evolution, or DNA segment shuffling, in which two or more existing genes break and re-join
to make a new hybrid gene, or horizontal (intercellular) transfer, in which a piece of DNA is
transferred from the genome of one cell to another (even between species). Each of these changes
leaves a characteristic trace in the DNA sequence.
Gene duplications give rise to families of related genes within a single cell
Accidents occasionally result in the inappropriate duplication of just part of the genome. Once a gene
has been duplicated, one of the two copies is free to mutate and become specialized to perform a
different function. Repeated rounds of this process of duplication and divergence enables one gene
to give rise to a gene family. When genes duplicate and diverge, the individuals of one species
become endowed with multiple variants of a primordial gene. This can lead to a branch point in the
family tree. Then, the genes gradually become different in the course of evolution, but they are likely
to continue to have corresponding functions in the different species. Genes that are related by
descent in this way are called orthologs. Related genes that have resulted from a gene duplication
event within a single genome are called paralogs. Genes that are related by descent in either way are
called homologs.
Genes can be transferred between organisms, both in the laboratory and in nature
Prokaryotes provide good examples of horizontal transfer of genes from one species of cell to
another. The most obvious are sequences recognizable as being derived from viruses, called
bacteriophages. Viruses are small packets of genetic material; they are not living themselves, bet they
often serve as vectors for gene transfer. A virus will replicate in one cell, emerge from it with a
protective wrapping, and then enter and infect another cell. Often, the infected cell will be killed, but
sometimes, the viral DNA may persist in its host for many cell generations, either as a plasmid, or as a
sequence inserted into the cell’s regular genome. In their travels, viruses can accidentally pick up
fragments of DNA from the genome of the host cell and ferry them into another cell. Horizontal
transfers do not seem to have played a significant part in eukaryote evolution, but it did have
significant impact on prokaryotes. Many prokaryotes have a capacity to take up even nonviral DNA
molecules from their surroundings.
Sex results in horizontal exchanges of genetic information within a species
In addition to the usual vertical transfer of genetic material from parent to offspring, sexual
reproduction causes a large-scale horizontal gene transfer between two initially separate cell lines:
the cell lines of both parents. Normally, this is within one species, but however it may occur, it leaves
an imprint: they result in individuals who are related more closely to one set of relatives with respect
to some genes, and more closely to another set with respect to others.
The function of a gene can often be deduced from its sequence
Family relationships among genes simplify the task of deciphering gene function, by comparing the
DNA sequences to known sequences. In many cases, the functions of one of more homolog genes is
already determined.
More than 200 gene families are common to all three primary branches of life
The complete genome sequences of representatives from all three domains (archaea, bacteria,
eukaryotes) can be used to look for homologies. But individual species have often lost some of the