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BASIC CELL BIOLOGY

LEARNING OUTCOMES

The following topics are covered in this chapter:

• Cellular structure and function;

• Chromosomes;

• The cell cycle;

• Deoxyribonucleic acid (DNA);

• Protein synthesis;

• Mitochondrial DNA.

INTRODUCTION

The activities that occur within cells give us an understanding of how human traits are inherited. Knowledge of cellular function gives rise to the understanding of how the body works. The human body is made up of trillions of cells, many of which have specialised functions. Despite this, all cells share certain features:

• cells arise from the division of pre-existing cells;

• cells interact, they send and receive information;

• cells produce proteins for growth repair and normal body functioning;

• cells contain all the genetic instructions for the body.

All cells in the body behave in this way apart from red blood cells. Red blood cells are not considered to be true cells by the time they reach the blood stream as they do not contain a nucleus. Cells are the basic building blocks of all living matter.

CELL STRUCTURE

Cells have many parts, each with a specialised function. Any structure within the cell that has a characteristic shape and function is termed an organelle. Most organelles are too small to be seen through a light microscope but can be seen with an electron microscope (see Figure 1.1).

Figure 1.1 Cell structure

Plasma membrane

This is the outer lining of the cell. It is composed of a bilipid layer through which certain molecules can enter the cell (endocytosis) and wastes can exit (exocytosis).

Figure 1.2 The outer lining of the cell

Nucleus

The nucleus functions as the control centre of the cell (Figure 1.3). It contains DNA (Deoxyribonucleic Acid) which is the cell’s genetic material. A double membrane separates the contents of the nucleus from the rest of the cell.This nuclear membrane (also called the nuclear envelope) is perforated by nuclear pores.

Figure 1.3 Nucleus

Nucleolus

The nucleolus (Figure 1.4) is a morphologically distinct area within the nucleus which is involved in the production of Ribonucleic Acid (RNA).

Figure 1.4 Nucleolus

Cytoplasm

Cytoplasm is a gel-like fluid that contains all the organelles and the enzymatic systems which provide energy for the cell.

Cytoskeleton

The cytoskeleton is a network of fibres made from the protein tubulin (Figure 1.5). This provides the structural framework of the cell and functions in cellular shape, cell division and cell motility, as well as directing movement of the organelles within the cell.

Figure 1.5 Cytoskeleton

Endoplasmic reticulum

The endoplasmic reticulum is an organelle that processes the molecules made by the cell (Figure 1.6). The endoplasmic reticulum transports these molecules to their specific destinations.

Figure 1.6 Endoplasmic reticulum

Ribosomes

Ribosomes are organelles that provide the sites for protein synthesis (Figure 1.7). Ribosomes are attached to the endoplasmic reticulum as well as freely floating in the cytoplasm.

Figure 1.7 Ribosomes

Golgi body

The Golgi body is a structure that packages the molecules produced by the endoplasmic reticulum ready for transport out of the cell (Figure 1.8).

Figure 1.8 Golgi body

Mitochondria

Mitochondria are organelles that convert energy gained from food into a form that the cell can use (Figure 1.9). Adenosine triphosphate (ATP) is the main source of energy used by the cell. These organelles have their own genetic material and can make copies of themselves.

Figure 1.9 Mitochondria

Lysosomes

Lysosomes are organelles that break down bacteria and other foreign bodies, as well as recycling worn out cell components (Figure 1.10).

Figure 1.10 Lysosomes

Peroxisomes

Peroxisomes are responsible for the detoxification of foreign compounds and the oxidation of fatty acids (Figure 1.11).

Figure 1.11 Peroxisomes

CHROMOSOMES

Each of the trillions of cells in the body, with the exception of red blood cells, has a nucleus. Within each nucleus are structures called chromosomes. Chromosomes are not usually visible under a light microscope, but when a cell is about to divide, the chromosomes become denser and can be viewed at this stage.

Chromosome structure

A chromosome is composed of DNA and proteins and includes structures that enable it to replicate and remain intact (see Figure 1.12). During cell division, chromosomes have a constriction point termed a centromere. The centromere divides each chromosome into two sections or ‘arms’. The long arm is referred to as the q arm and the short arm as the p arm (p for petite).

The location of the centromere gives the chromosome its characteristic shape and can be used to describe the location of specific genes.

Figure 1.12 A chromosome

Telomeres

Telomeres are distinctive structures found on the end of each arm of the chromosome. They are made up of the same short sequence of DNA, which is replicated about three thousand times. The function of the telomeres appears to be twofold.

1. They protect the chromosome by ‘capping’ off the ends to prevent them from sticking or joining onto other chromosomes.

2. Due to the way that chromosomes are replicated, the ends of the chromosomes are not copied. Telomeres shorten during every cell replication, but the loss of DNA within the telomeres protects against loss of essential DNA within the chromosome itself.

Chromosome numbers

Chromosomes exist in pairs. Although not actually joined together, each pair has a characteristic length. The human cell nucleus has 23 pairs of chromosomes; in other words, 46 individual chromosomes. One chromosome from each pair is inherited from the father and one from the mother. Twenty-three individual chromosomes are inherited from each parent. The total number of chromosomes in each cell is called the diploid number (diploid 46) while the number of pairs is called the haploid number (haploid 23).

Of the 23 pairs of chromosomes, 22 pairs are termed autosomes and do not differ between the sexes. For ease of identification, these autosomes are numbered from 1 to 22. The chromosomes are numbered according to length, with chromosome number 1 being the longest and chromosome 22 being the shortest. The remaining two chromosomes are known as the sex chromosomes. These two chromosomes are not numbered but are known as the X chromosome and the Y chromosome. The Y chromosome determines maleness. A female will have two X chromosomes while a male will have one X and one Y chromosome.

Karyotype

The chromosome complement within the nucleus is called a karyotype. Charts called karyographs (see Figure 1.13) display chromosomes in pairs in size order. The 22 paired autosome chromosomes are displayed first, ranging from number 1 to 22 (largest to the smallest). The sex chromosomes, X and Y (male) or X and X (female) are always placed at the end of the chart. Karyographs can be a useful clinical tool to help confirm diagnosis through the identification of chromosomal aberrations, abnormalities or anomalies.

Figure 1.13 A karyograph

The centromere

Another physical characteristic of the chromosome, the centromere, also helps identification, as the position of the centromere varies in different chromosomes (see Figure 1.14).

Figure 1.14 Centromere positions

ACTIVITY 1.1

What are the haploid and diploid numbers of chromosomes in humans?

CHROMOSOMAL INHERITANCE

The human cell has two sets of chromosomes, one set inherited from each parent. The complete genetic makeup within the cell is termed the genome. The total number of chromosomes within the cell has to be kept constant from one generation to the next. Each individual has a total of 46 chromosomes in each cell nucleus, 23 of which are inherited from their mother and 23 from their father.

For normal cell division two daughter cells are formed, both of which have the full 46 chromosome complement. This type of cell division is called mitosis and results in new cells that are genetically identical to the parent cell. Mitosis is cell division that is used by the body for growth and repair. Meiosis, on the other hand, is a type of cell division that produces new cells with only half the chromosomal complement (a total of 23 chromosomes). These 23 chromosomes are half the set of the original cell. Meiosis only occurs in the germ line cells, i.e. the ova in women and the sperm in men. If fertilisation occurs, the resulting offspring will inherit 23 chromosomes from the mother and 23 chromosomes from the father, resulting in a full 46 chromosomal complement. Meiotic division prevents the doubling of chromosomal numbers from one generation to the next.

Mitosis

Mitosis occurs rapidly during growth and tissue repair. It is a well-controlled process and consists of two major steps – the division of the nucleus followed by the division of the cytoplasm. Although mitosis is a continuous process it can be described as a series of four stages followed by a resting period where there is no cellular division (Table 1.1).

Table 1.1 The stages of mitosis and interphase

Stages	Events
	Chromosomes get shorter and fatter by coiling themselves. They now become visible under a light microscope. Each chromosome has two strands (two copies of the original chromosome) that are held together by the centromere. Strands of protein called spindle fibres appear.
	Chromosomes line up together and the spindle fibres become attached to each side of the centromere.
	The spindle fibres contract, pulling the two copies of each chromosome to opposite areas within the nucleus.
	The two new sets of chromosomes form two new nuclei. The chromosomes revert to being long and thin. The cytoplasm then divides to form two new cells.
	Normal cellular function. The cells make copies of their chromosomes ready for the cycle to start again.

With mitosis each daughter cell is an exact copy of the previous cell. All cells receive identical chromosomal material.

The cycle of events during mitosis usually lasts several hours. The mitotic division of the chromosomal material during prophase, metaphase, anaphase and telophase takes a relatively short period of time and the resting phase (interphase) takes up most of the time within the cell cycle (see Figure 1.15).

Figure 1.15 The cell cycle

The whole cell cycle takes approximately 24 hours, although this depends on which type of cell is involved. Mitosis usually only accounts for about an hour. Interphase is when no cellular division takes place. However, even during interphase, the cell needs to get ready for division so it increases in size. This stage is known as Gap 2 or G2. After division the cell needs to continue to grow so that it can achieve its optimum size; this is known as Gap 1 or G1.

Normally cells can undergo a total of 80 mitotic divisions before the cell dies, although this is dependent on the age of the individual.

Meiosis

Each cell contains two sets of chromosomes which exist in pairs. Meiosis results in cell division that produces new cells with only half the chromosomal complement. This is needed for the formation of germ cells (sperm in men, ova in women) so that two germ cells can fuse to form a full chromosomal complement.

Halving the full complement is achieved in two steps called meiosis I and meiosis II. Meiosis I is very similar to mitotic division in that two daughter cells are produced, both with 46 chromosomes. The main difference is that meiosis I takes much longer in comparison to mitosis and results in the ‘crossing over’ of chromosomal material (see Figure 1.16). Chromosomes ‘swap’ or exchange pieces of their structure with their partner chromosome before separating. This results in the daughter cells not having identical genetic material. This is the cause of genetic variability between individuals.

Meiosis II does not involve chromosomal replication but does involve the stages of prophase, metaphase, anaphase and telophase where chromosomes separate, new nuclei are formed and the cell splits into two. At the end of meiosis II the cells contain 23 individual chromosomes.

Figure 1.16 Crossing over

Differences between mitosis and meiosis

The differences between mitosis and meiosis are illustrated in Figure 1.17 and Table 1.2.

Figure 1.17 Mitosis and meiosis

Table 1.2 The differences between mitosis and meiosis

Mitosis	Meiosis
one division	two divisions
results in 2 daughter cells	results in 4 daughter cells/gametes
genetically identical	genetically different
same chromosome number	chromosome number halved
occurs in all body cells	occurs only in germ cells
occurs throughout life	occurs only after sexual maturity
used for growth and repair	used for production of gametes

ACTIVITIES 1.2, 1.3 AND 1.4

1.2. Explain why there is significant genetic variation as a result of meiosis but not of mitosis.

1.3. Describe the phases of the cell cycle.

1.4. Explain the reason why germ cells have to undergo meiotic division.

GENETIC INFORMATION

Chromosomes are made up of long chains of DNA (Deoxyribonucleic Acid) and protein molecules. It is the DNA within the chromosomes that holds all genetic information. The total length of the DNA within each cell is over 2m (6 feet) and, in order to fit within the cell’s nucleus, it has to exist in a tightly packaged form. This is achieved by the DNA being coiled around protein structures called histones (see Figure 1.18). The DNA wraps around eight histones to form a structure called a nucleosome. Thousands of nucleosomes are formed, which gives the DNA molecule the appearance of a string of beads. Further coiling of these nucleosome beads results in a shortened structure called a chromatin fibre. It is these tightly packaged chromatin fibres that make up chromosomes.

Figure 1.18 Histones, nucleosomes and chromatin fibre

The DNA within the chromosomes contains coded instructions for the production of protein. The coded area for the production of a specific protein is called a gene.

The structure of DNA

The structure of DNA was discovered through X-ray diffraction back in 1953 by the Nobel Prize-winning scientists James Watson and Francis Crick. DNA is composed of bases, sugars and phosphates that combine together to form a double helix. The double helix shape looks like a twisted ladder. The ‘sides’ of the ladder are made of phosphates and sugars, while the ‘rungs’ of the ladder are made of bases. Only four different types of bases exist within the DNA:

• Adenine (A);

• Guanine (G);

• Cytosine (C);

• Thymine (T).

DNA bases pair up with each other to form the ‘ladder rungs’ (see Figure 1.19). Adenine always pairs with Thymine, and Guanine always pairs with Cytosine. Only these two types of base pairing exist in DNA. The order of the base ‘rungs’ along the DNA ladder varies but the base pairings are always complementary.

Figure 1.19 DNA bases

The sequences of bases on one DNA strand can be deduced from the sequence on the opposite strand, because base pairing is always complementary. Each strand independently carries the information required to form a double helix. Therefore, to describe a DNA sequence, only the sequence of the bases in one strand is needed, for example ATTGCAAT, as the other strand is always complementary, i.e. TAACGTTA. Human DNA consists of about 3 billion bases, of which over 99 per cent of the sequence is identical in all people. These bases, within the DNA, form the code for the production of proteins.

PROTEIN

All the functions of the cell depend on protein. Protein maintains cell structure, acts as both intracellular and extracellular messengers, binds and transports molecules and acts as enzymes.

Some proteins exist in every cell, such as the enzymes involved in glucose metabolism. Other proteins are highly specialised and are only found in specialised cells, such as the protein myosin, found only in muscle cells, or the protein insulin that is only produced in pancreatic islet cells.

What are proteins?

Proteins are made up of long chains of amino acids. There are only 20 different types of amino acids but, by varying the order and amount of amino acids in the chain, thousands of different proteins can be produced.

Links within the chain of amino acids are called peptide bonds, while the chain itself is known as a polypeptide. A protein can contain one or more polypeptides. Both the structure and function of the protein depend on the sequence of the amino acids making up the polypeptide chains.

In order to function, cells need information to produce proteins and the ability to pass this information on to new cells during cell division. This important information is provided by the DNA.

How are proteins made?

Proteins are not made in the cell nucleus but by the ribosomes in the cell’s cytoplasm. The coded information in the DNA has to be transferred out of the nucleus. This is done by the use of ribonucleic acid (RNA).

Step 1: Copying the code

Segments of the DNA within the chromosomes separate at specific points and the DNA code is copied. This copy is called the messenger RNA (mRNA). During this process Guanine pairs with Cytosine and Adenine pairs with Uracil. RNA does not have Thymine but this is replaced with Uracil. Once a copy has been made, the DNA reattaches and the mRNA makes its way out of the nucleus into the cytoplasm (see Figure 1.20).

Figure 1.20 Copying the code (transcription)

Step 2: Reading the code

Once out in the cytoplasm, the mRNA attaches itself to a ribosome. Also present in the cytoplasm are amino acids, which are attached to a different type of RNA called transfer RNA (tRNA). The tRNA is only a short molecule of three bases that is attached to a corresponding amino acid. If the messenger RNA, which is attached to the ribosome, has three codes that correspond to the code on the transfer RNA, then the amino acid will be released by the transfer RNA. The released amino acid will then join other amino acids through the same process to form a protein molecule (see Figure 1.21).

Figure 1.21 Reading the code (translation)

Figure 1.22 Making the protein

Step 3: Making the protein

When a peptide bond has been formed between amino acids they detach from the transfer RNA. The protein will now be constructed (see Figure 1.22).

Table 1.3 Summary of the main processes

Structure	Process	Function
DNA	None	Carries the genetic code
Messenger RNA (mRNA)	Transcription	Copies the code for a single protein from the DNA. Carries the copied code to the ribosomes
Ribosome	Translation	Reads the mRNA code and assembles the correct amino acid sequence
Transfer RNA (tRNA)	None	Brings individual amino acids from the cell cytoplasm to the ribosomes

The RNA code is written in a trinary code. Three bases code for one amino acid; this is known as a codon. There are four bases in RNA (Adenine, Guanine, Cytosine and Uracil) so a total of 64 possible combinations of codons can be achieved. As there are only 20 different types of amino acids, some amino acids can be coded for by more than one codon. This is referred to as degeneracy in the genetic code.

Some codons do not code for any amino acids but act as a start or stop signal. AUG (Adenine, Uracil, Guanine) has been recognised as a start codon and UAG, UGA and UAA act as stop codons.

The RNA base code for all amino acids has been deciphered since the 1960s and is known as the universal genetic code (see Figure 1.23).

The universal genetic code is based on the codons from the RNA where Uracil has replaced the Thymine base in the DNA. There is only one type of DNA whereas there are three different types of RNA (Table 1.4).

• mRNA: messenger RNA is a direct copy of DNA that codes for specific amino acids.

• tRNA: transfer RNA carries amino acids from the cytoplasm to the ribosomes.

• rRNA: ribosomal RNA facilitates interaction between mRNA and tRNA.

Figure 1.23 The universal genetic code

Table 1.4 The main differences between DNA and RNA

DNA	RNA
double stranded	single stranded
deoxyribose sugar	ribose sugar
includes Thymine	includes Uracil
exists in one form	exists in different forms

ACTIVITIES 1.5 AND 1.6

1.5. The following table shows the sequence of bases on part of an mRNA molecule:

Base sequence on mRNA	CCU CAA AGU GGU GUU CGA
Base sequence on DNA

a. Complete the table to show the DNA base sequence.

b. By using the universal genetic code table in this chapter, identify which amino acids are coded for.

1.6. A particular strand of mRNA is 60 bases long. How many amino acids would this strand code for?

MITOCHONDRIAL DNA

Not all the DNA in the human cell is contained within the chromosomes in the cell nucleus. Mitochondria, in the cell’s cytoplasm, have their own DNA (the mitochondrial genome). This very small amount of DNA in the mitochondria is only inherited from the mother. Mitochondrial DNA is not inherited directly from the father as the mitochondria are placed in the tail of the sperm, which does not penetrate the ovum. In exceptional circumstances, when the tail of the sperm does manage to enter the ovum, the mitochondria are destroyed in the very early stages of embryo development.

The DNA within the mitochondria encodes for proteins that are essential for mitochondrial structure and function. This is a very small genome and most of the mitochondrial proteins are coded for by the nuclear genome.

THE CLASSIFICATION OF GENETIC MATERIAL

For any cellular structure to be classified as genetic, it must display four characteristics.

1. Replication.

2. Storage of information.

3. Expression of the stored information.

4. Variation.

1. Replication: this is achieved through the cell cycle when chromosomes are replicated in order to produce new cells.

2. Storage of information: chromosomes store all the information needed for the production of proteins. The genetic material within cells does not necessarily express all the stored information in every cell, only what is appropriate for that individual cell. For example, eye colour is not expressed in every cell, only in the cells which make up the iris of the eyes and the protein actin is only expressed in muscle cells and not in any other type of cell.

3. Expression of the stored information: expression is a complex process. Information flow requires DNA, RNA and cellular proteins (see Figure 1.24).

4. Variation: Genetic variation includes rearrangements between and within chromosomes as well as ‘crossing over’ during meiosis. This gives rise to trait variations between individuals and populations.

Chromosomes are the body’s genetic material as they possess all four characteristics.

Figure 1.24 Expression of stored information

ACTIVITIES 1.7 AND 1.8

1.7. Explain and contrast a chromosome and a gene.

1.8. Identify the role of the following cellular components in the storage, expression and transmission of genetic information:

• chromatin;

• nucleus;

• ribosome;

• mitochondrion;

• centromere.

SUMMARY

• Cells are made up of organelles and chromosomes.

• Chromosomes are composed of DNA that encodes for proteins.

• There are 23 pairs of chromosomes in the nucleus of every cell (46 in total). There are 44 autosomes (22 pairs) and 2 sex chromosomes (X and Y).

• 23 individual chromosomes are inherited from each parent.

• Cells replicate to produce identical cells by mitosis. To halve the chromosomal number in germ cells, the cells replicate by meiosis.

• There are four different bases included in the DNA structure. A sequence of three bases (a codon) code for one amino acid. Amino acids link together to form protein.

• RNA is needed to copy and carry the genetic code out of the nucleus and to assemble the amino acid chain within the cytoplasm.

• Proteins are assembled following transcription and translation of the genetic code.

• Mitochondria have their own genome, although most mitochondrial proteins are coded for by the nuclear genome.