Genetics: the Code Broken

GENETICS: THE CODE BROKEN?

KEY WORDS AND TERMS USED IN THIS TOPIC

As you study this topic you should write the definitions for the following syllabus terms.

Term / Definition
polypeptide
gene expression
multiple alleles
ABO blood groups
the Rhesus factor
polygenic inheritance
DNA fingerprinting
diploid
haploid
somatic cells
gametic cells
dihybrid crosses
linked genes
chromosome mapping
Human Genome Project
recombinant DNA
gene therapy
trisomy
polyploidy
mutation
base substitution mutations
frameshift mutations
transposable genetic elements
germ line mutations
somatic mutations
gene cloning
whole organism cloning
selective breeding
gene cascades
gene homologues

GENETICS: THE CODE BROKEN?

SUMMARY OF THIS TOPIC

In this option, polypeptide synthesis is revised, as is the structure of the DNA molecule. Polypeptide synthesis is also referred to as ‘gene expression’, because this is when the information in the original DNA molecule actually expresses itself. Gene expression is regulated by the action of other ‘regulatory’ genes, which produce proteins that can control the transcription stage and other aspects of protein synthesis.

Characteristics can be determined by more than one pair of alleles (‘multiple alleles’) within a gene pair; examples of this include the inheritance of blood groups and Rh antigens on the red blood cells. This situation differs from ‘polygenic inheritance’, which occurs when many alleles, often located on different chromosomes, control the inheritance of a particular characteristic. Examples of this include the inheritance of human height and skin colour. The greatest degree of genetic variation between two organisms occurs in the non-coding regions of the DNA molecule known as ‘introns’, and these regions are consequently used to compare two individuals in DNA fingerprinting techniques.

Somatic (body) cells contain the full complement of chromosomes, known as the ‘diploid’ number, whereas gametes (sex cells) contain only half this number (i.e. the ‘haploid number’). Genes can be inherited on different chromosomes or, in the case of ‘linked’ genes, on the same chromosome. Typical Mendelian ratios do not occur when inheritance patterns of linked genes are traced; these patterns can in fact be used to construct gene linkage maps to determine the relative position of linked genes along a chromosome.

An even more detailed study of gene locations is being carried out by the Human Genome Project.

This task involves mapping all the genes in the human genome, working out the DNA sequence of

each gene, and identifying disease-causing genes. Recombinant DNA technology can also be used to

locate the positions of genes on chromosomes and the actual nucleotide sequence on the DNA molecule.

Modern genetic techniques have also enabled the development of ‘gene therapy’, a process which involves altering the genetic makeup of an individual. Although mostly still in the trial stage, treatments for diseases such as cystic fibrosis, cancers and genetic diseases are showing promise.

The genetic makeup of an individual can change through various types of mutations, often producing harmful effects on human health. Examples of such harmful mutations include Down’s syndrome, muscular dystrophy and sickle-cell anaemia. Despite this, genes damaged during DNA replication are continually being repaired by special DNA repair genes, which act to either restore damaged bases or remove and replace them. Genes may also be changed when sections of DNA (‘transposable elements’) move from one part of the genome to another.

Humans, through selective breeding and cloning, can also alter the genomes of plants and animals by favouring particular genes over others. Gene cloning, which uses genetic engineering techniques to produce multiple copies of a desired gene, can also be used to produce transgenic organisms with completely different genomes to the original ones.

The stages of embryonic development are controlled by different sets of genes; regulatory genes appear to control the expression of other genes, with the result that not all genes are expressed during each stage of an organism’s development. Studies of regulatory genes such as ‘HOX’ genes and other genes have also helped scientists to determine evolutionary relationships between organisms.

GENETICS: THE CODE BROKEN?

MAJOR OBJECTIVES OF THIS TOPIC

As indicated in the HSC Biology syllabus, the major outcomes of this topic include the ability to:

·  describe the main stages of polypeptide formation, and the roles of DNA and RNA in this process

·  construct a model of DNA

·  explain current ideas about gene expression

·  describe the inheritance of a trait controlled by multiple alleles in an organism other than humans

·  solve problems relating to the inheritance of ABO blood groups and the Rhesus factor in humans

·  describe an example of polygenic inheritance

·  explain how variable genes are used in DNA fingerprinting to discern genetic differences between organisms

·  explain the terms ‘haploid’, ‘diploid’, ‘somatic’ and ‘gametic’ cells

·  solve problems involving dihybrid crosses of independently inherited and linked genes

·  outline the use of gene linkage maps and explain how they can be made using the results of experimental crosses

·  discuss the main objectives and limitations of the Human Genome project

·  explain how recombinant DNA is produced and outline how this technology is used to locate genes on chromosomes

·  describe the use of gene therapy in the treatment of a genetic disease, a named form of cancer, or AIDS

·  describe the effects of mutations on human health, and describe the following types of mutations:

-  rearrangements

-  changes in chromosome number

-  base substitution

-  frameshift

·  outline the role of DNA repair genes

·  explain how transposable genetic elements can alter the genome

·  describe the difference between germ line and somatic mutations in terms of their effect on the genome

·  describe how selective breeding, cloning and gene cloning can alter the genetic makeup of a particular species

·  trace the history of the selective breeding of a particular agricultural species

·  describe the process involved in animal cloning

·  explain how embryonic development is controlled by genes, including the role of gene cascades in limb formation

·  describe how the occurrence of gene homologues in different species can be used to trace evolutionary relationships

1) The structure of a gene provides the code for a polypeptide

The role of DNA in polypeptide synthesis

The steps involved in polypeptide synthesis are outlined in chapter 2. Recall that the stages involved in this process are as follows:

·  DNA in the nucleus ‘unzips’, exposing unpaired nitrogen bases.

·  Messenger RNA copies the code on a single stranded DNA molecule in the nucleus. This process is known as transcription. RNA is single stranded and contains a ribose instead of a deoxyribose sugar.

·  The messenger RNA moves from the nucleus and attaches itself to the small subunit of a ribosome in the cytoplasm.

·  Transfer RNA molecules carry a ‘triplet’ of bases at one end. Each triplet codes for a particular amino acid, and these are picked up by the tRNA molecules in the cytoplasm.

·  The transfer RNA molecules match up with their complementary base triplets on the messenger RNA.

·  Further amino acids, carried by their transfer RNAs, become attached to the messenger NA and are joined to each other by peptide bonds.

Eventually, a chain of amino acids is formed. This process is known as translation. Fig. 6-1 shows the main steps involved in protein synthesis, and Table 6-1, below, explains some of the terms commonly used.

transcription / process where the information on a single DNA strand is copied by a mRNA molecule
translation / process in which polypeptides are assembled on the ribosome using the information in the mRNA molecule
messenger RNA / a type of RNA that carries the genetic code from DNA in the nucleus to the ribosome in the cytoplasm
transfer RNA / a type of RNA that carries amino acids to the ribosome
code / the sequence of bases in a DNA molecule
codon / a set of three bases on DNA or mRNA
anticodon / a set of three bases that complements a codon; found on tRNA molecules

Table 6-1 Terms used in polypeptide synthesis

ii)

i) iii)

Fig. 6-1 Polypeptide synthesis. In i), the DNA code is being copied by mRNA; in ii), mRNA moves to a ribosome in the cytoplasm; in iii), tRNA carries amino acids to the ribosome where the base triplets match up- here, the amino acids will link together to form a polypeptide

THINK!!! In a segment of one strand of a DNA molecule, the base sequence is CAA CTA GAA. What would be the sequence of bases in a mRNA molecule that has been transcribed from the DNA? (Remember that in RNA the base uracil replaces thymine).

·  As a requirement of this topic, you need to perform a first-hand investigation to construct a model of DNA.

James Watson, Frances Crick and Maurice Wilkins received the Nobel Prize in 1962 for working out the structure of the DNA molecule. Their model revealed DNA as a double stranded helix, consisting of alternating sugar and phosphate groups which are linked by pairs of nitrogen bases. Each strand of the molecule is complementary to the other one; that is, the base sequence on one strand is complementary to the base sequence on the other. Guanine (G) always pairs with cytosine (C), and adenine (A) always pairs with thymine (T). Fig. 6-2, below, shows how a model of a DNA can be made using pegs of four different colours, wool or string, and shapes to represent sugar or phosphate groups.

Fig. 6-2 Making a model of DNA

The current understanding of gene expression

When the information in a gene is actually used to manufacture a particular polypeptide, we say it is being expressed. During the life of an organism, many genes are only expressed at certain times; during adolescence, for example, the genes responsible for the production of hormones will become ‘switched on' to a greater degree. Once gene expression commences, transcription of the DNA code onto a messenger RNA and translation of this code into a series of amino acids on the ribosome will occur. Current knowledge of this process recognises the fact that gene expression is regulated by the action of other genes. These regulatory genes produce proteins that bind to ‘control element’ segments of the gene in question and either activate it or suppress its expression. Most gene regulation occurs during the transcription step of polypeptide synthesis, and involves ‘transcription factor’ genes. The regulatory proteins produced by these genes can control the number of RNA transcripts produced, the rate of transcription and which section of the DNA molecule is copied. By recognising the first and last codons in the gene, the regulatory proteins can also turn the transcription process on or off, thus controlling the length of the messenger RNA formed. Gene regulation also controls other aspects of gene expression such as the splicing of the initial large mRNA to remove the coding sequences (exons) from the non-coding sequences (introns). This process can affect the type of protein that is ultimately produced. Other points of control include the selection of mRNA molecules that undergo translation on the ribosome and the activation or inactivation of the actual proteins that have been made.

Within the control element section of a gene, there are regulatory sequences and promoter sequences. The regulatory sequence is the region regulatory proteins bind to when controlling the expression of a gene. The promoter sequence is a region at the start of the gene that makes sure DNA polymerase transcribes the DNA in the correct direction during the transcription process.

2) Multiple alleles and polygenic inheritance provide further variability within a trait

Multiple alleles: ABO blood groups and the Rhesus factor

Multiple alleles occur when a characteristic is determined by more than one pair of alleles within a gene pair. In humans, for example, blood groups are determined by three different alleles; A, B and O. The combination of these alleles can result in four different blood groups- A, B, AB or O. Group A has the genotype IAi or IAIA, group B can be IBi or IBIB, and group O is ii. Group AB has the genotype IAIB and is an example of co-dominance of both genes. Blood in each group except for group O contains antigens on the surface of the red blood cells; group A contains A antigens, group B contains B antigens and group AB contains both A and B antigens. Group O blood contains Antibody A and Antibody B, group A contains Antibody B, group B contains Antibody A, while group AB contains no antibodies. As a result, care must be taken when administering blood transfusions that blood types are not incompatible (see table 6-2). A person with group A blood, for instance, cannot receive blood from group B or group AB because Antibody B in the recipient’s blood will react with the B antigen present in the donated blood and cause the blood to agglutinate.

Another set of proteins found on the red blood cells is determined by at least eight alleles. These are called the Rh antigens, and the lack of antigen D (the ‘rhesus factor’) in a mother’s blood can result in a condition known as haemolytic anaemia in newborn babies. A person without antigen D is referred to as being Rh negative (genotype rr), while those possessing the antigen are Rh positive (genotypes RR or Rr). If an Rh negative mother is carrying an Rh positive embryo, she may develop antibodies against antigen D during childbirth, which can be harmful to subsequent Rh positive babies she may carry. Rh positive babies can only arise if the father has the genotype RR or Rr.

A method now used in hospitals involves injecting an Rh negative mother with Rh antibodies so she does not need to make her own. This means that her antibodies are not present in subsequent pregnancies.

Group / Antigen present / Antibody present / Can donate blood to: / Can receive blood from:
A / A / B / A, AB / A, O
B / B / A / B, AB / B, O
AB / A, B / none / AB / AB, O, A, B
O / none / A,B / A, B, AB, O / O

Table 6-2 The compatibility of various blood group combinations