lecture 5 dna, genes and genomes - sham nairshamnair.com/biol115_2014_lecture-5_dna.pdf ·...

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)

Biol115_2014_Lecture 5 2

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


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!!


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.


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).


So, what is a gene?


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


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


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



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.


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.


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.


Extensive variation in genome size within

and among the main groups of life


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


Alternative splicing: expressing several proteins from a single gene.


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


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


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


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.


lecture 5 dna, genes and genomes - sham nairshamnair.com/biol115_2014_lecture-5_dna.pdf ·...

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