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2.3  Chemicals that Make Cells Work

The genetic code is composed of DNA that is packaged into functional units called

“genes.” Each gene in essence has a DNA sequence that can be read out to manufacture

a specific type of peptide or protein. The total collection of all genes in a given cell in an

organism is in general the same across different tissues in the organism (though note that

some genes may have altered functions due to local environmental nongenetic factors called

“epigenetic modifications”) and referred to as the genome. Genes are marked out by start

(promoter) and end points (stop codon) in the DNA sequence, though some DNA sequences

that appear to have such start and end points do not actually code for a protein under

normal circumstances. Often, there will be a cluster of genes between a promoter and stop

codon, which all get read out during the same gene expression burst, and this gene cluster

is called an “operon.”

This presence of large amounts of noncoding DNA has accounted for a gradual decrease

in the experimental estimates for the number of genes in the human genome, for example,

which initially suggested 25,000 genes has now, at the time of writing, been revised to more

like 19,000. These genes in the human genome consist of 3 × 10⁹ individual base pairs from

each parent. Note, the proteome, which is the collection of a number of different proteins in

an organism, for humans is estimated as being in the range (0.25–​1) × 10⁶, much higher than

the number of genes in the genome due to posttranscriptional modification.

KEY POINT 2.10

Genes are made from DNA, which code for proteins. The genome is the collection of

all individual genes in a given organism.

DNA also exhibits higher-​order structural features, in that the double helix can stably form

coils on itself, or the so-​called supercoils, in much the same way as the cord of a telephone

handset can coil up. In nonsupercoiled, or relaxed B-​DNA, the two strands twist around the

helical axis about once every 10.5 base pairs. Adding or subtracting twists imposes strain,

for example, a circular segment of DNA as found in bacteria especially might adopt a figure-​

of-​eight conformation instead of being a relaxed circle. The two lobes of the figure-​of-​eight

conformation are either clockwise or counterclockwise rotated with respect to each other

depending on whether the DNA is positively (overwound) or negatively (underwound)

supercoiled, respectively. For each additional helical twist being accommodated, the lobes

will show one more rotation about their axis.

In living cells, DNA is normally negatively supercoiled. However, during DNA replica­

tion and transcription (which is when the DNA code is read out to make proteins, discussed

later in this chapter), positive supercoils may build up, which, if unresolved, would prevent

these essential processes from proceeding. These positive supercoils can be relaxed by special

enzymes called “topoisomerases.”

Supercoils have been shown to propagate along up to several thousand nucleotide base

pairs of the DNA and can affect whether a gene is switched on or off. Thus, it may be the case

that mechanical signals can affect whether or not proteins are manufactured from specific

genes at any point in time. DNA is ultimately compacted by a variety of proteins; in eukaryotes

these are called “histones,” to generate higher-​order structures called “chromosomes.” For

example, humans normally have 23 pairs of different chromosomes in each nucleus, with

each member of the pair coming from a maternal and paternal source. The paired collection

of chromosomes is called the “diploid” set, whereas the set coming from either parent on its

own is the haploid set.

Note that bacteria, in addition to some archaea and eukaryotes, can also contain sev­

eral copies of small enclosed circles of DNA known as plasmids. These are separated from

the main chromosomal DNA. They are important biologically since they often carry genes

that benefit the survival of the cell, for example, genes that confer resistance against cer­

tain antibiotics. Plasmids are also technologically invaluable in molecular cloning techniques

(discussed in Chapter 7).