GENOMICS
1.3 Genome: d (ii) Genomics
From the Arrangements
(ii) Genomics
Many genomes have been sequenced, particularly of disease -causing
organisms, pest species and species that are important model organisms for
research.
Comparisons of genomes reveal that much of the genome is highly conserved
across different organisms.
Teacher’s notes
This section is based on the summary questions on page 5.
There are two activities related to these questions. The first is to read the
background information card and answer the questions.
Alternatively, do not print off the background information but get the
students to research the answers to the questions using the internet. Less-able
students could be given a copy of the suggested websites.
Print the background information back to back. These printouts could be
reused.
UNIT 1, PART (III) GENOME (H, BIOLOGY)
© Learning and Teaching Scotland 2011
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GENOMICS
Background information
Human genomes
The human genome project culminated in 2003 after 13 years of work costing
three billion dollars. The project included work on human diseases, model
organisms such as bacteria, yeast, worms, flies and mice, the development of
new technologies for biological and medical research, such as computing, and
programming power to analyse mind boggling amounts of complex data.
Perhaps less than 2% of the three billion base pairs codes for the 20 000 to
25 000 genes we are estimated to have. Much of the DNA has, as yet, no
known function.
In 2007 Craig Venter’s genome was published. Within his genome there were
4.1 million variations, 3.2 million being single nucleotide polymorphisms
(SNPs; single base substitutions) the rest being deletions, insertions and
duplications. Over a million of these variations were previously unknown.
The project took about ten years and cost 100 mi llion dollars.
In 2008, James Watson’s genome was published; it cost 1.5 million dollars
and took just four months. In December of 2010 a personal genome machine
for less than 50 000 dollars came onto the market that will sequence your
genome in less than two weeks at a cost of less than 10 000 do llars. No doubt
as the technology advances hospitals or even health centres will be able to
diagnose genetically complex predispositions such as cancers, diabetes and
neurological disorders, and to optimise treatments or advise life management
systems within the space of a day. It is interesting to note that Watson started
to take cholesterol-lowering drugs straightaway after he had his DNA
sequenced but did not want to know about any of his genes which may be
linked to Alzheimer’s disease.
Early sequencing technology relied on radioactive nucleotides and X -ray film
for determining the order of bases. The next generation of sequencers used
fluorescent dyes and laser optics instead of radioactive isotopes. In turn
fluorescent dyes have been superseded by semi-conductor sequencers that
rely on chemical rather than optical means of reading the sequence.
Comparative genomics
In early 2011, the genomes of over 1000 prokaryotes and over 300 eukaryotes
were published with many more in the pipeline. Soon all the m ajor crop and
farm animals along with all their main disease -causing organisms will have
their genome sequences stored in huge computer databases.
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UNIT 1, PART (III) GENOME (H, BIOLOGY)
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GENOMICS
Comparative genome sizes of humans and other model organisms
Taken from http://www.nature.com/scitable/knowledge/library/comparative genomics-13239404.
Organism
Human
(Homo sapiens)
Mouse
(Mus musculus)
Estimated
size (base
pairs)
Chromosome
number
Estimated
gene number
3 billion
46
~ 25 000
2.9 billion
40
~ 25 000
165 million
8
13 000
157 million
10
25 000
97 million
12
19 000
12 million
32
6 000
4.6 million
1
3 200
Fruit fly
(Drosophila
melanogaster)
Plant
(Arabidopsis thaliana)
Roundworm
(Caenorhabditis
elegans)
Yeast
(Saccharomyces
cerevisiae)
Bacteria
(Escherichia coli)
From the table, Arabidopsis has a smaller genome than the fruit fly but twice
as many genes: about the same as a human. An important lesson, therefore, is
that genomic size, or the number of genes, is not proportional to an
organism’s place on the evolutionary tree. However, by using powerful
software it is possible to recognise individual genes within genomes and to
compare these genes between species.
Fruit flies are thought to share 60% of their genes with humans, in other
words we share a core set of genes with a fly. Furthermore, about two -thirds
of genes known to be involved with cancer have also been found in fruit flies.
By studying how these genes work in a much simpler orga nism we should get
a better understanding of how these genes operate in humans and therefore be
able to control or prevent them becoming diseased.
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GENOMICS
The Japanese puffer fish (Fugu rubripes) has a genome eight times smaller
than humans but with a similar number of genes: it lacks any lengthy
repetitive sequences. About 75% of puffer fish genes have a human
equivalent even though men and fish diverged from their common ancestor
450 million years ago. This has proved to be a useful model organism since
the puffer fish genome project has revealed about a thousand new genes in
the human genome.
At the DNA level humans and chimpanzees are remarkably close. Most of the
differences are thought not to be in the genes but in regions of the DNA
which control the genes. One study compared highly conserved regions of
DNA in mice, rats and chimpanzees. The sequences that are conserved (the
same or similar) between species are thought to be important to the organism
since selection pressures have kept them, whereas mutati ons generally occur
much more frequently in non-coding regions. The study also took the
chimpanzee sequences and compared them to the same human sequences and
found 202 ‘highly accelerated regions’ (HARs) that showed higher rates of
variation between humans and chimpanzees. The region with the most
differences makes a piece of RNA that has a role in brain development.
Amazingly, only three of these HARs are thought to contain sequences
encoding proteins, the rest are located very close to genes. This analysis was
carried out using computer software to compare the data with that of other
research groups. There is no doubt that DNA sequencing will reveal much
about our developmental processes and evolution.
In addition to brain development, the other major differences between
humans and chimpanzees are in the immune system. This is thought to be due
to an evolutionary ‘arms race’: viruses and bacteria evolve very quickly so
the human immune system has been under selection pressures to positively
match new pathogenic threats. Since humans live in a much wider range of
environments and behave differently to chimp anzees, humans have been
exposed to a much wider assortment of pathogens and consequently have a
more sophisticated defence system.
Genomics will reveal much to scientists. Agriculturalists will improve crop
yields and engineer crops to be resistant to specific diseases, pests or
environmental factors such as global warming or drought resistance. Energy
production in terms of biomass will benefit. Farm a nimal production may be
improved – preventative medicines to tackle their associated diseases will be
developed. This branch of veterinary medicine will no doubt run parallel to
advances in human medicine.
All this will be made possible with the advance of powerful computers and
their software to manipulate sequence data. So far the science of
bioinformatics makes it possible to search genome databases with gene
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UNIT 1, PART (III) GENOME (H, BIOLOGY)
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GENOMICS
sequences, to compare gene sequences from different organisms, to build up
the complete genome sequence for an organism and to assess the variation
between individual’s genomes and between the genomes of two different
species. In the future it will allow us to predict how genes are regulated, how
proteins will be synthesised, how they will fold and function in the cell, and
how they will interact with other molecules , be they natural or synthetic.
Without computers the secrets of the genome would remain undiscovered.
Learning objectives
By answering these questions you should know that the genomes of many
organisms, including humans, have been sequenced , especially:
 those of economic importance, such as farm crops and animals
 the disease-causing organisms of farm crops and farm animals
 simpler organisms that act as models to help unravel the human genome.
You should understand that many genes are very similar from organism to
organism and these are said to be conserved.
Summary questions
Use the background information card or the internet to answer these
questions.
1.
In terms of base pairs how big is the human genome?
2.
In Craig Venter’s case how many genetic variations were found in his
genome?
3.
What sort of genetic predispositions will health centres be able to
diagnose in the future?
4.
What drugs did James Watson start to take once his genome h ad been
sequenced?
5.
How many organisms have had their genomes sequenced to date?
6.
Is there any relationship between the size of an organism’s genome and
its place in the evolutionary tree, ie the bigger the genome the more
advanced the organism?
UNIT 1, PART (III) GENOME (H, BIOLOGY)
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GENOMICS
7.
What percentage of genes in a fruit fly is thought to be shared with
humans?
8.
What advantages for human medicine may come out of studying fruit
fly genomics?
9.
How many new human genes have been discovered by studying the
puffer fish genome?
10.
Why is the puffer fish a good model organism to study human genes?
11.
Where are most of the differences between chimpanzee DNA and
human DNA thought to be located?
12.
What does conserved mean when talking about genes?
13.
What are the two main differences between humans and chimp anzees?
14.
Give examples of how genomics will help improve agriculture and
medicine.
15.
What is meant by ‘bioinformatics’?
Suggested websites
Try Googling ‘James Watson’s genome’ or ‘Craig Venter’s genome’.
Look at the links below. Rather than type in the whole IP address Google the
main part of the address then find the correct (or similar) links in your search
results.
http://www.nature.com/scitable/knowledge/library/ comparative-genomics13239404
http://www.news.cornell.edu/stories/May05/Chimps.kr.html
http://www.sciencedaily.com/releases/2006/10/061013104633.htm
http://www.genomenewsnetwork.org/articles/08_02/pufferfish_genome.shtml
Some of these web sites may be text heavy but G oogling the question or key
words in the question will quickly get you the answer.
Remember to stay focused on the 15 questions. These suggested websites are
only a starting point!
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UNIT 1, PART (III) GENOME (H, BIOLOGY)
© Learning and Teaching Scotland 2011