Human Physiology, 14th edition (2016)

Cell Structure and Genetic Control 63

“promoter” regions, which are sites that participate in the

regulation of nearby genes. Other stretches of DNA serve as

“enhancer” regions that regulate the expression of distant genes.

There are also stretches of DNA that comprise jumping genes,

or retrotransposons, that make copies of themselves during

cell division and insert these copies randomly into the genome,

thereby changing genetic expression. In the performance of

these and other functions, most of the genome that lies outside

of the historical definition of genes (the protein-coding regions)

is transcribed into RNA at some time.

Until recently it was believed that one gene coded for one

polypeptide chain (recall that some proteins consist of two or

more polypeptide chains; see fig. 2.28 e, for example). How-

ever, each cell produces well over 100,000 different proteins,

so the number of proteins greatly exceeds the number of genes.

The term proteome has been coined to refer to all of the pro-

teins produced by the genome. This concept is complicated

because, in a given cell, some portion of the genome is inac-

tive. There are proteins produced by a neuron that are not pro-

duced by a liver cell, and vice versa. Further, a given cell will

produce different proteins at different times, as a result of sig-

naling by hormones and other regulators.

So, how does a gene produce more than one protein?

This is not yet completely understood. Part of the answer may

include the following: (1) a given RNA coded by a gene may

be cut and spliced together in different ways (see fig. 3.17 ),

a process called alternative splicing discussed shortly;

(2) a particular polypeptide chain may associate with differ-

ent polypeptide chains to produce different proteins; (3) many

proteins have carbohydrates or lipids bound to them, which

alter their functions. There is also a variety of posttransla-

tional modifications of proteins (made after the proteins have

been formed), including chemical changes such as methyla-

tion and phosphorylation, as well as the cleavage of larger

polypeptide chain parent molecules into smaller polypeptides

with different actions. Scientists have estimated that an aver-

age protein has at least two or three of such posttranslational

modifications. These variations of the polypeptide products

of a gene allow the human proteome to be many times larger

than the genome.

Part of the challenge of understanding the proteome is iden-

tifying all of the proteins. This is a huge undertaking, involving

many laboratories and biotechnology companies. The func-

tion of a protein, however, depends not only on its composi-

tion but also on its three-dimensional, or tertiary, structure (see

fig. 2.28 d ) and on how it interacts with other proteins. The

study of genomics, proteomics, and related disciplines will

challenge scientists into the foreseeable future and, it is hoped,

will yield important medical applications in the coming years.

Chromatin

DNA is composed of four different nucleotide subunits that

contain the nitrogenous bases adenine, guanine, cytosine, and

thymine. These nucleotides form two polynucleotide chains,

joined by complementary base pairing and twisted to form a

membranes are fused together by structures called nuclear
pore complexes. These structures function as rivets, holding
the two membranes together. Each nuclear pore complex has
a central opening, the nuclear pore ( fig. 3.13 ), surrounded by
interconnected rings and columns of proteins. Small molecules
may pass through the complexes by diffusion, but movement
of protein and RNA through the nuclear pores is a selective,
energy-requiring process that requires transport proteins to
ferry their cargo into and out of the nucleus.
Transport of specific proteins from the cytoplasm into the
nucleus through the nuclear pores may serve a variety of func-
tions, including regulation of gene expression by hormones (see
chapter 11). Transport of RNA out of the nucleus, where it is
formed, is required for gene expression. As described in this
section, genes are regions of the DNA within the nucleus. Each
gene contains the code for the production of a particular type of
RNA called messenger RNA (mRNA). As an mRNA molecule
is transported through the nuclear pore, it becomes associated
with ribosomes that are either free in the cytoplasm or associ-
ated with the granular endoplasmic reticulum. The mRNA then
provides the code for the production of a specific type of protein.
The primary structure of the protein (its amino acid
sequence) is determined by the sequence of bases in mRNA.
The base sequence of mRNA has been previously determined
by the sequence of bases in the region of the DNA (the gene)
that codes for the mRNA. Genetic expression therefore occurs
in two stages: first genetic transcription (synthesis of RNA)
and then genetic translation (synthesis of protein).
Each nucleus contains one or more dark areas ( fig. 3.13 ).
These regions, which are not surrounded by membranes, are
called nucleoli. The DNA within the nucleoli contains the
genes that code for the production of ribosomal RNA (rRNA).

Genome and Proteome

The term genome can refer to all of the genes in a particu-
lar individual or all of the genes in a particular species. From
information gained by the Human Genome Project, scientists
currently believe that a person has approximately 25,000 dif-
ferent genes. Genes have historically been defined as regions
of DNA that code (through production of mRNA) for poly-
peptide chains. The Human Genome Project was completed
in 2001, and as of 2014 scientists have found about 20,000
protein-coding genes in humans, far fewer than the number
previously assumed. Scientists were surprised to learn that the
protein-coding regions comprise little more than 1% of the
genome. The rest was initially thought to be “junk DNA,” but
this idea was erroneous. A project called ENCODE (for the
Encyclopedia of DNA Elements) is cataloguing the function
of these elements. This project has shown that at least 80% of
the human genome performs some function other than coding
for mRNA and proteins. A more inclusive definition of “gene”
would include DNA regions that encode any type of RNA.
Part of the genome codes for RNA molecules that attenu-
ate the translation of mRNA (such as microRNA, discussed
shortly), thereby regulating gene expression. Part serves as