lecture 5 dna, genes and genomes - sham nairshamnair.com/biol115_2014_lecture-5_dna.pdf ·...
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Biol115The Thread of Life
Lecture 5
DNA, genes and genomes
“So that's when I saw the DNA model for the first time, in the Cavendish, and
that's when I saw that this was it. And in a flash you just knew that this was very
fundamental.Sydney Brenner
Principles of Biology
• Chapter ‘Genomics’
• Chapter ‘Genome Diversity’
• Chapter ‘Gene Expression’ (From genes to traits)
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Objectives
• Explain how species traits like size or complexity are not necessarily related to genome size.
• Define gene density and explain how it varies between eukaryotes and prokaryotes.
• Explain how an organism is able to make many more different kinds of proteins than it has genes in its genome.
• Explain how a species as complex as humans appears to have the same number of genes as a microscopic parasite.
• Key terms: gene density, genome, gene, genotype, promoter, regulatory regions, open reading frame, introns, exons, systems biology
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What is a gene?
• Genes are carried on chromosomes, and DNA is the molecule of heredity.
So, what exactly is a gene?
• Hermann Muller showed that X-rays caused mutations in genes.
• Beadle and Tatum showed that when the bread mould, Neurospora
crassa, was irradiated with X-rays, it was not able to make some enzymes.
• Beadle and Tatum concluded that each gene contained information for
making one enzyme (one gene-one enzyme hypothesis).
• Since enzymes are proteins, this was extended to the one gene-one
protein hypothesis). Nowadays, even this has been rephrased as the one
gene-one polypeptide hypothesis). Recently, this has been changed, yet
again!!
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Arginine synthesis
Beadle and Tatum studied mutant Neurospora that could not synthesize arginine. The mold
had three different mutations, each in a different enzyme of a biochemical pathway. Each
enzyme was encoded by a different gene.
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So, what is a gene?
Genes ….
• specify biological traits (Mendel’s pea experiment, Griffiths’
bacterial transformation experiment).
• Are contained in chromsomes (sex-linkage, sex
determination).
• When damaged by X-rays, fails to produce enzymes (proteins).
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So, what is a gene?
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The gene is the basic physical and functional unit of heredity. It
consists of a specific sequence of nucleotides at a given position on a
given chromosome that codes for a specific protein (or, in some cases,
an RNA molecule).
The structure of genes
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Genes consist of three parts:
• coding regions, called exons, which specify a sequence of amino
acids
• non-coding regions, called introns, which do not specify amino acids
• regulatory sequences, which play a role in determining when and
where the protein is made (and how much is made)
Note: prokaryotic genes do not contain exons and introns. Each prokaryotic gene
contain a single , uninterrupted coding region
Prokaryotic genes• Prokaryotes ‘read’ genes from an uninterrupted stretch of
nucleotides = open reading frame (ORF) = coding region
Coding region (dark green) = ORF = codes for a single polypeptide.
Regulatory regions (lime green) = flank ORF and regulate the expression of the gene.
5’ 3’
http://www.ncbi.nlm.nih.gov/bookshelf/picrender.fcgi?book=mga&part=A132&blobname=ch2f4.jpg
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Eukaryotic genes
• The region of DNA that encodes a single polypeptide is often separated into
discrete portions by intervening non-expressed DNA.
• polypeptide encoding portions of DNA = exons (EXpressed DNA)
• non-polypeptide encoding portions of DNA = introns (INTervening DNA)
5’ 3’
http://www.ncbi.nlm.nih.gov/bookshelf/picrender.fcgi?book=mga&part=A132&blobname=ch2f4.jpg
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The polypeptide-encoding sequences of DNA are laid out in different
ways by prokaryotes and eukaryotes.
http://www.ncbi.nlm.nih.gov/bookshelf/picrender.fcgi?bo
ok=mga&part=A132&blobname=ch2f4.jpg
Completed
genomes
Genome: All the hereditary
information of an organism; may
include both chromosomal DNA and
extrachromosomal DNA, and also
coding DNA and noncoding DNA.
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Extensive variation in genome size within and among the main groups of life
• Eukaryotic genomes vary dramatically in terms of size
and gene counts.
• Eukaryotic genome sizes vary enormously and that this
is unrelated to intuitive ideas of morphological
complexity.
• Largest known genome: Paris japonica
152,230,000,000 bp
• In prokaryotes, genome size and gene number are
strongly correlated, but in eukaryotes the vast majority
of nuclear DNA is non-coding.
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Extensive variation in genome size within and among the main groups of life
• As with genome size, having more protein-coding genes does
not necessarily translate into greater complexity. This is
because the eukaryotic genome has evolved other ways to
generate biological complexity (e.g. alternative splicing) –
discussed in a later lecture.
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Extensive variation in genome size within
and among the main groups of life
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The genome sizes of 9,000 species
is now available. The figure
illustrates the means and overall
ranges of genome size that have
been observed so far in the main
groups of living organisms, and are
loosely arranged according to
common ideas of complexity to
further emphasize the disparity
between this parameter and genome
size.
Number of genes does not correlate with complexity
Species and Common Name Estimated Total Size of Genome (bp)* Estimated Number of Protein-
Encoding Genes*
Yeast 12 million 6,000
Malaria parasite 23 million 5,000
Nematode 95.5 million 18,000
Fruit fly 170 million 14,000
Mustard 125 million 25,000
Rice 470 million 51,000
Chicken 1 billion 20,000-23,000
Dog 2.4 billion 19,000
Mouse 2.5 billion 30,000
Human 2.9 billion 20,000-25,000
Water flea 200 million 35,000
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Alternative splicing: expressing several proteins from a single gene.
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Even though it is
translated from a
single gene, the
information within
an mRNA
transcript can be
rearranged during
mRNA splicing.
The final mRNA
would be
translated into a
protein with a
different number or
order of protein
subunits than what
was coded for by
the pre-spliced
mRNA.
The Drosophila Dscam gene, involved in
adhesion between neurons, contains 4
clusters of exons, each with array of
possible exons. These are spliced into the
mRNA in an exclusive fashion, so that
only one of each of the possible exons is
represented. If all combinations of these
exons are used in alternative splicing, the
Dscam gene can produce 38,016 different
proteins.
Eukaryotes have relatively more DNA per cell
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Genome of Propionibacteria
(yellow and green lines indicate
open reading frames)
Gene clustering on maize chromosomes. Each chromosome
has been divided into 2-μm intervals. The maize genome is
2,500 000 000 bp in length.
Eukaryotic genomes contain much non-coding DNA
Characteristic Bacteria (E.coli) genome Human genome
Genome Size (base pairs) 4.6 Mb 3.2 Gb
Chromosome Structure Circular Linear
Number of chromosomes 1 46
Number of genes 4,288 20,000
Presence of Introns No Yes
Average Gene Size 700 bp 27,000 bp
Percentage of genome that
codes for proteins65 1.5
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Human DNA function
Only a very small fraction of human DNA encodes proteins. A
large fraction contains either introns or transposons.Biol115_2014_Lecture 5 20
Why do eukaryotes have more DNA than
prokaryotes?Non-expressed DNA can be:
(1) pseudogenes - non-functional copies of “normal”
genes
(2) introns within genes
(3) highly repetitive DNA sequences between genes -
satellites and microsatellites
(4) large regulatory regions upstream and downstream
of genes
(5) structural: forming critical regions within
chromosomes;
e.g. centromeres and telomeres = 10% of total DNA
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telomere
centromere
Systems biology
Interactions of proteins among various flagellate bacteria.Biol115_2014_Lecture 5 22
Systems biology
Interactions of drugs, host genomes, and bacterial genomes
can influence disease outcomes.Biol115_2014_Lecture 5 23
SummaryBy now, you should be able to:
• Define the term ‘gene’ and how it is a fundamental concept that links classical genetics, molecular genetics and genomics.
• Compare and contrast prokaryotic and eukaryotic gene architectures.
• Explain what genomes are and how such information is gathered.
• Explain why the numbers of genes encoded in genomes are not a true reflection of organismic complexity.
• Explain why eukaryotes contain more DNA in their genomes and what their roles may be.
• Describe the goals of systems biology.
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