Lec.

, 2

The organization and

structure of genomes
Genetics: study of inherited phenotypes.
Genomics: study of genomes.
• Genome – The complete set of sequences in the
genetic material of an organism.
– It includes the sequence of each chromosome plus any
DNA in organelles. (genomic DNA isolation, gDNA)
• Transcriptome – The complete set of RNAs
present in a cell, tissue, or organism.
– Its complexity is due mostly to mRNAs, but it also
includes noncoding RNAs.
• Proteome – The complete set of proteins that is
expressed by the entire genome.
– The term is sometimes used to describe the complement
of proteins expressed by a cell at any one time.
--omics the science study each one
Genomics, transcriptomics, proteomics
 Introduction,… continued
Prokaryotes and Eukaryotes genomes,
Prokaryotes Eukaryotes
Single cell Single or multi cell
No nucleus Nucleus
No organelles Organelles
One piece of circular DNA Chromosomes
No mRNA post transcriptional Exons/Introns splicing
modification
In bacteria, mRNA is polycistronic; mRNA is usually monocistronic

– Polycistronic: one mRNA codes for more than one polypeptide

– moncistronic: one mRNA codes for only one polypeptide

Generally organelles genome (cpDNA and mtDNA)

looks likes prokaryotes genome
 Prokaryote genomes
• E. coli contains amount of 4X106 base pairs (4000Kb)
• > 90% of DNA encode protein
• 4,285 genes, 122 structural RNA genes
• Circular and supercoiled DNA
• Lacks a membrane-bound nucleus.
• Histones not present
• Contain one large circular piece of DNA referred to as a
"chromosome" (not a true chromosome).
• Many bacteria have small circular DNA structures called
plasmids which can be exchanged between neighbors
and across bacterial species
 Eukaryotic genome
• Example: C. elegans, 10 chromosomes
• 19,099 genes, Coding region – 27%
• Average of 5 introns/gene
• Both long and short duplications
A small fraction of the total DNA encodes protein.
•Many repeats of non-coding sequences
 All chromosomes are contained in a membrane
bound nucleus
•DNA is divided between two or more chromosomes

A set of five histones

•DNA packaging and gene expression regulation
Eukaryotic organism Nuclear chromosome
DNA
Mitochondria
chromosome (mtDNA)
Chloroplast
chromosome
(cpDNA)
Genes in
Mitochondria : Oxidative
phosphorylation ATP

Chloroplast : Photosynthesis

Content : small
Human nuclear chromosome : 3,000,000 Kb (100,000 genes)
Human mtDNA : 17Kb (37 genes)
• “Control Center”
Nucleus
• Contains chromosomes
• Nuclear genome
Individual Genomes Show Extensive Variation
• Single Nucleotide Polymorphism (SNP) –
polymorphism (variation in sequence between individuals)
caused by a change in a single nucleotide, responsible for
most of the genetic variation between individuals.
• Polymorphism may be detected at the phenotypic level
when a sequence affects gene function..
• haplotype – The particular combination of alleles in a
defined region of some chromosome; in effect, the genotype
in miniature.
• Will studied in more detailed latter
 Some organelles have DNA
• Mitochondria and chloroplasts have genomes that show
non-Mendelian inheritance. Typically they are maternally
inherited.
• Extranuclear genes – Genes that reside outside the
nucleus, in organelles such as mitochondria and chloroplasts.
• Comparisons of human mitochondrial DNA suggest that it is
descended from a single population that existed ~200,000
years ago in Africa.
• Organelle genomes are usually (but not always)
circular molecules of DNA.
– Mitochondrial DNA (mtDNA)
– Chloroplast DNA (cpDNA or ctDNA)
• Organelle genomes encode some, but not all, of the
proteins used in the organelle.
 Mitochondria
Singular: Mitochondrion
• “Powerhouse” of the cell
• Produces energy in the form of ATP

• Primary site of oxidative phosphorylation

• Contains own genome
• No recombination
• No introns
• Variable control region
• Own genetic code
• Animal mtDNA is extremely
compact and typically encodes
13 proteins, 2 rRNAs, and 22
tRNAs.
• D loop – A region of the animal
mtDNA molecule that is variable
in size and sequence and
contains the origin of replication.
• Yeast mtDNA is 5× longer than
animal cell mtDNA because of
the presence of long introns.
 Diversity of mitochondrial genomes

Plants Fungi Animals

Size 14kb - 42kb 17kb - 180kb 184kb - 2,400kb

Non-coding DNA Very Low Variable Very High

Mutation rate High Low Very Low

Recombination  / 

Introns   

Universal genetic code  Mostly 

 Mitochondrial DNA
• Mitochondrial DNA is a single double stranded circular
molecule.
• There are several copies in each mitochondrion and there are
many mitochondria in each of your cells.
• Mitochondrial DNA is similar to prokaryotic DNA. There are
no histones or any other protein associated with mt DNA.
• The genes contain no introns. Maternal inheritance.
• Because it is in a highly oxidizing environment it has a much
higher rate of mutations than nuclear DNA.
• The genes in mt DNA code for mitochondrial ribosomes and
transfer RNAs.
• Some genes code for polypeptide subunits of the electron
transport chain common to all mitochondria.
 Chloroplast
• Site of photosynthesis
• Plant cells ONLY
• Contains the pigment chlorophyll

1 µm

Electron microscopic image of a circular DNA

molecule isolated from a soybean chloroplast (a ctDNA)
Chloroplast Biology-Structure
1. double-membrane envelope
2. stroma: large soluble interior
3. thylakoid membrane system
4. intrathylakoid space or lumen
thylakoid membrane envelope

stroma
II. Functions
1. many important biochemical (anabolic)
pathways, e.g.,
photosynthesis*
starch synthesis
fatty acid synthesis*
amino acids synthesis
pigment synthesis*
nucleotide synthesis
nucleic acids* and protein synthesis
sulfur and nitrogen assimilation
2. own genetic system*
* Indicates that pathway involves a chloroplast
encoded gene in at least some organisms
 V. Chloroplast Genetics
1. Inheritance is typically uniparental, usually maternal.
Multiple mechanisms involved, not well understood:
- in Chlamydomonas (next slide), the paternal (-) cpDNA
is destroyed, and the maternal (+) cpDNA is
preferentially replicated
- in some land plants, the paternal plastids are excluded
during fertilization or absent from the sperm cell
2. Essentially all plastids have DNA, usually the same DNA
throughout the organism (homoplasmy).
3. The DNA sequence does not change during differentiation.

There are exceptions to the last 2 statements.

 Chloroplast DNA (cpDNA)

General features:
1. double-stranded, circular molecule
2. no histones, but have bound proteins (e.g.,
Hu), organized into nucleoids
3. G-C content typically less than nuclear DNA
4. multiple copies (~30-100) per plastid (i.e., all
cp genes are multi-copy)
5. can be 10-20% of the total DNA in leaves
 The Chloroplast Genome Encodes Many
Proteins and RNAs
• Chloroplast genomes vary in size, but are large enough to
encode 50 to 100 proteins as well as rRNAs and tRNAs.

The chloroplast genome in land

plants encodes 4 rRNAs, 30 tRNAs,
and ~60 proteins.
Mitochondria and Chloroplasts Evolved by
Endosymbiosis

• Both mitochondria and chloroplasts

are descended from bacterial
ancestors.
• Most of the genes of the mitochondrial
and chloroplast genomes have been
transferred to the nucleus during the
organelle’s evolution.

Mitochondria originated by a endosymbiotic event when a

bacterium was captured by a eukaryotic cell.
 Extranuclear Inheritance
The past couple of lectures, we’ve been exploring
exceptions to Mendel’s principles of transmission
inheritance.
Scientists have observed inheritance patterns that
do not fit either Mendelian principles or the
extensions of Mendelian genetics.
Now that DNA has been discovered in places outside
the nucleus, these phenomena are explained.
 Maternal (Organelle) Inheritance
DNA contained in mitochondria or chloroplasts
determines the phenotype of the offspring.

These phenotypes arise due to the source of

organelles—only from the egg—such that
there is only a maternal influence on
phenotype.
Genome structure - Chromatin
Genetic Information: Chromosomes

– (1) Double helix DNA strand.

– (2) Chromatin strand (DNA with histones)
– (3) Condensed chromatin during interphase with centromere.
– (4) Condensed chromatin during prophase
– (5) Chromosome during metaphase
Chromosome

Condenced scaffold

fibers connected to
chromosome scaffold

chromatin fibers

chromatin

DNA
 Genome structure - Chromosomes
Human cells have 46 chromosomes: 22 normal
chromosomes (autosomes), in pairs (from father
and mother), and two sex chromosomes (X from
the mother, X or Y from the father).

In preparation for normal cell division (mitosis),

chromosomes are replicated, but remain joined
at their centromere (prophase). This gives the
chromosomes their “X” shape. Both “halves” of
the X are called (sister) chromatids.

When cells are not replicating, this is the usual form

of chromosomes.

http://biology.unm.edu/ccouncil/Biology_124/Summaries/Sex.html
The DNA content of the
haploid genome.
.

The minimum genome size found in

a range of organisms
 Chromosomes
Organism Number of base pair number of Chromosomes (in pairs)
---------------------------------------------------------------------------------------------------------
Prokayotic
Escherichia coli (bacterium) 4x106 1
Eukaryotic
Saccharomyces cerevisiae (yeast) 1.35x107 17
Drosophila melanogaster(insect) 1.65x108 4
Homo sapiens(human) 2.9x109 23
Zea mays(corn) 5.0x109 10

• Bacteria 1 • Fox 34
• Fruit fly 8 • Mouse 40
• Garden Pea 14 • Rat 42
• Yeast 16 • Rabbit 44
• Frog 26 • Human 46
• Cat 38 • Chicken 78
 Genome structure - Genes
Darwin (1809-1882) used the term “gemmule” to denote a microscopic
unit of inheritance. Major problem in his day: why do traits not
“blend out” by mixing.

Mendel (1822-1884) first to suggest the existence of factors conveying

traits from parent to offspring, and the pattern of their inheritance
(e.g., two copies per individual, one from each parent; segregation
during gamete production; different traits segregate independently),
solving the problem of blending.

1889: Hugo de Vries coined term “pangen”, later shortened to “gene”.

1910: Thomas Hunt Morgan: genes reside on specific chromosomes
1941: Specific genes code for specific proteins. “One gene one enzyme” hypothesis.
1977: Roberts and Sharp discover introns
2003: Genes often overlap; single genes have multiple product.
 The Central Dogma
• One gene, one protein
• Like most dogmas, not entirely true
• Alternative splicing permits the manufacture
of many products from a single gene
• The protein products are sometimes called
the proteome
• With current technology, more gene
information is available than protein
information
Central Dogma ‫معادلة الحياة‬
 Replication
Transcription Translation
Dupilcation DNA RNA Protein
Reverse transcription
Differences in gene expression between prokaryotes and eukaryotes
Translation and Translation and
transcription occur at transcription occur
same time separatly

Polypeptide chain
• In the genes of many eukaryotes, the protein-
encoding sequence is interrupted by uncoding
sequences DNA called introns. The origin and
functions of introns are still unclear. They are
excised (removed or splicing) from the primary
transcript during the formation of mRNA. The
segments of coding sequence between the
introns are called exons.
Gene (cistron) the fundamental unit of genetic function.
Gene (muton) the fundamental unit of genetic mutation.
Gene (recon) the fundamental unit of genetic recombination.
Gene (codon) the fundamental unit of genetic coding.

Gene (cistron) is the segment of DNA involved in producing a

polypeptide chain; it includes regions preceding and
following the coding region (leader and trailer) as well as
intervening sequences (introns) between individual coding
segments (exons).
Allele is one of several alternative forms of a gene occupying a
given locus on a chromosome.
Locus is the position on a chromosome at which the gene for a
particular trait resides; locus may be occupied by any one
of the alleles for the gene.
 Eukaryotic Gene Structure
Start Codon Stop Codon
Cis- ATG TAA, TAG, TGA
Regulatory
Elements
Exon1 Exon2 Exon3
Promoter/
Enhancer 5’ UTR 3’ UTR

Exon1 Exon2 Exon3

Start Codon Stop Codon

polyA tail
Exon1 Exon2 Exon3 AAAAAAAA
5’ UTR 3’ UTR
 structure of a eukaryotic gene

promoter

This example has three introns and four exons

Structure genes (which are transcripted,)

Functional genes (which control gene transcription like

promoter and terminator(
 Genes

• A gene: DNA sequence that is needed to encode amino acid

sequence of a protein
Eukaryotic protein-coding genes consist of:
• Promoter region, with transcription initiation site
• 5’ untranslated region (5’ UTR)
• Translation initiation site (includes start codon)
• Alternating sequence of exons (protein- coding) and introns
• Translation stop site (stop codon)
• 3’ UTR
• Polyadenylation (poly-A) signal
• Translation stop site
 Types of exons
Transcription start polyA Stop
5’ GT AG GT AG GT AG GT AG
Gene
3’
promoter
Open reading frame
Initial exon
Internal exon
Internal coding exon
Terminal exon
Translation Translation
Start Stop

mRNA 5’ 3’

5’ untranslated Protein 3’ untranslated

region coding region
region
 structure of a eukaryotic gene

promoter

This example has three introns and four exons

Structure genes (which are transcripted,)

Functional genes (which control gene transcription like

promoter and terminator(
 Gene action in eukaryotic cell
• Outside the nucleus of the cell is a complex array
of membranous structures, including the
endoplasmic reticulum and Golgi apparatus, and
organelles such as mitochondria and
chloroplasts. The nucleus contains most of the
DNA, but note that mitochondria and
chloroplasts also contain small chromosomes.
Each gene encodes a separate protein, each with
specific functions either within the cell
View of gene action in a eukaryotic cell.
View of gene action in a eukaryotic cell.
• The basic flow of genetic information is from
DNA to RNA to protein. Four types of genes are
shown. Gene 1 responds to external regulatory
signals and makes a protein for export; gene 2
responds to internal signals and makes a protein
for use in the cytoplasm; gene 3 makes a protein
to be transported into an organelle; gene 4 is
part of the organelle DNA and makes a protein
for use inside its own organelle.
• Some protein-encoding genes are transcribed
more or less constantly; these are the
“housekeeping” genes (typically constitutive
genes that are required for the maintenance of
basic cellular function) , that are always needed
for basic reactions, like Lactate dehydrogenase A,
also known as LDHA, is an enzyme in human.
• Other genes may be rendered to suit the
functions of the organism at particular times and
under particular external conditions. The signal
that masks or unmasks a gene may come from
outside the cell.