The Structure and Organization of Genomes

Genome = The totality of DNA in a cell.

—ome = the full set of <something> in

the cell or genome of an organism

… and new ‘omes are still being defined

The Structure and Organization of Genomes

Genome: The totality of DNA in a cell.

Chromosome: Continuous threads of DNA in a cell or nucleus
Karyotype: Chromosome complement an of individual (often photographed at
metaphase showing the chromosomes arranged by size).

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 The Structure and Organization of Genomes

Genome: The totality of DNA in a cell.

Chromosome: Continuous threads of DNA in a cell or nucleus
Karyotype: Chromosome complement an of individual (often photographed at
metaphase showing the chromosomes arranged by size).

Prokaryotic vs. Eukaryotic Genomes

Domains of Life (groups above Kingdoms): Archaea, Bacteria, Eukaryotes

1. DNA of eukaryotes is contained in a membrane-

bound nucleus

2. Eukaryotes contain other membrane-bound

organelles (mitochondria, chloroplast, Golgi)
3. Prokaryotes have a rigid plasma membrane
whereas eukaryotes have a semi-permeable
membrane with an internal cytoskeleton.

The Structure and Organization of Genomes

Genome: The totality of DNA in a cell.

Chromosome: Continuous threads of DNA in a cell or nucleus
Karyotype: Chromosome complement an of individual (often photographed at
metaphase showing the chromosomes arranged by size).

Prokaryotic vs. Eukaryotic Genomes

Domains of Life (groups above Kingdoms): Archaea, Bacteria, Eukaryotes
Eukaryotes

Archaea
Bacteria

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 Features of some sequenced genomes
Species Genome size (mb) # of Genes
Eukaryotes (41, up from 37 last yea r )
Arabidopsis thaliana 125 25,500
Caenorhabditis elegans 97 19,000
Drosophila melanogaster 108 13,600
Homo sapiens 3200 32,000
Saccharomyces cerevisiae 12 5,800

Bacteria (341, up from 233 last year )

Escherichia coli 4.64 4,400
Mycobacterium tuberculosis 4.41 4,000
Mycoplasma genitalium 0.58 500
Pseudomonas aeruginosa 6.26 5,700
Streptococcus pneumoniae 2.16 2,300
Vibrio cholerae 4.03 4,000
Yersinia pestis 4.65 4,100

Archaea (27, up from 23 last year )

Archaeglobus fulgidus 2.18 2,500
Methanococcus jannaschii 1.66 1750
Nanoarchaeum equitans 0.49 550

Plus there are 976 “ongoing” bacterial genome sequencing projects,

629 eukaryotic & 57 archaeal (and 50+ “metagenomic” datasets)

Sizes (C-values) of assorted genomes

Species Genome size (kb)

Navicola pelliculosa (diatom) 35,000
Drosophila melanogaster (fruitfly) 180,000
Parameciumaurelia (ciliate) 190,000
Gallus domesticus (chicken) 1,200,000
Cyprinus carpio (carp) 1,700,000
Boa constrictor (snake) 2,100,000
Rattus norvegicus (rat) 3,100,000
Xenopus laevis (toad) 3,100,000
Homo sapiens (bubba) 3,200,000
Nicotiana tabaccum (tobacco) 3,800,000
Paramecium caudatum (cilate) 8,600,000
Allium cepa (onion) 18,000,000
Lilium formosanum (lily) 36,000,000
Amphiuma means (newt) 68,000,000
Pinus resinosa (pine) 84,000,000
Protopterus aethiopicus (lungfish) 140,000,000
Ophioglossum petiolatum (fern) 160,000,000
Amoeba dubia 670,000,000

What is the source of the variation in genome sizes?

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 Cot curves can show the nature of sequences in a genome
DNA is purified, sheared and melted into single strands, and then allowed to
renature by gradual cooling. % of reassociated dsDNA (y-axis) is shown as a
function of the product of DNA concentration and time (x-axis)

Foldback DNA

Highly Repetitive DNA

Middle Repetitive

Single copy DNA

Determining the relative amounts of repetitive & scDNA via Cot curves

Species C value (gb) %scDNA

Tetrahymena pyriformis 0.2 90
Aplysia californica 1.8 55
Drosophila melanogaster 0.2 60
Limulus polyphemus 2.7 70
Gallus domesticus (chicken) 1.2 80
Ciona intestinalis 0.2 70
Bufo bufo 6.9 20
Xenopus laevis 3.1 75
Mus musculus 3.4 70
Homo sapiens (bubba) 3.4 64

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 Classes of Repetitive Elements in Eukaryotes
Highly repetitive: long rows of short repeats (100s bp, 10000s of copies)
Middle repetitive: longer repeats, tandem/dispersed, some transpose (1000s bp)
Mini- or Microsatellites: few tandem copies of simple sequence repeats (10s bp)
Gene & segmental duplications: multiple copies of genes/regions that have a
common ancestry (related function, multigene family) (up to 100000s bp)

Types of Repetitive Elements Prevalent in Mammalian Genomes

Classes & Ages of Repetitive Elements in Mickey & Bubba

How might it be possible to determine the age of repetitive elements in a genome?

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 Have any functions been ascribed to this large non-coding fraction?
1. Correlation between C-value and (i) duration of meiosis and mitosis, (ii)
metabolic rate, (iii) generation time, (iv) development time in lizards, seed size
and CO2 response in plants, morphological complexity in amphibian brains
2. Genome architecture, e.g., for the spacing and regulation of genes
3. “Junk” DNA with no function (Ohno 1972)
4. “Selfish” DNA, which is actively maintained by intragenomic selection

How do the copy numbers of repeats increase?

1. “Passive” processes: unequal crossing over; replication slippage
2. “Active” processes by transposable elements: replicative transposition
(via a DNA intermediate); retrotransposition (via an RNA intermediate)

Types of genome-wide repeats in the human genome

(adapted from Brown, Table 1.2)

Type of Repeat Subtype Number of Copies

SINES Alu 1,190,000
100 – 300 bp MIR 393,000
GC-rich, No RT MIR3 75,000

LINES LINE-1 516,000

3 – 5 kb LINE-2 315,000
AT-rich LINE-3 37,000

LTR elements ERV class 1 112,000

Retrotransposons EVR(K) 8,000
Encode RT EVR(L) 83,000
MaLR 240,000

DNA transposons hAT 195,000

Tc-1 75,000
PiggyBac 2000
_____________________________________________________________

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 Contents of a eukaryotic genome
(adapted from Page & Holmes, Molecular Evolution, 1998)

Single copy genes

Multicopy RNA genes Tandem
Coding DNA
Multigene families
Regulatory sequences Dispersed

Satellite
Tandem repeats Minisatellites
Non-coding DNA Transposons (& retroelements) Microsatellites
Spacer DNA (& non-coding within genes)

Large scale expansions in eukaryotic genomes:

multigene families & segmental duplications

Are eukaryotic genomes ever-expanding?

Are there any limits to genome size?
What are the determinants of overall genome size?

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 Bacteria differ from eukaryotes in genome organization
and in having very little repetitive DNA

Human

Yeast

Fruit fly

Maize

E. coli

Figure 2.2 from Brown, page 34

Structure and Organization of Genomes: Chromosomes

Chromosome features:

• Number (variation among species)

• Size (variation within genome)
• Centromere Position (p,q arms)
• Variable (orange) regions (within species)
• Banding patterns (G,R,Q,C)

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Structure and Organization of Genomes: Isochores

Structure and Organization of Genomes: Isochores

________________________________________________
Fraction % GC % Genomea % Genes Gene densityb
________________________________________________

L1 38% 30% —
} 34% 1 per 100 kb
L2 41% 32% —

H1 44% 21% —
} 38% 1 per 50 kb
H2 49% 10% —

H3 53% 3% 39% 1 per 6.4 kb

________________________________________________
a
Remaining portion of the genome corresponds to satellite and
ribosomal sequences.
b
Calculations were based on a 3 gigabase genome containing
50,000 (!?!) genes.

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 Organellar Genomes

Species Size (kb) # Genes

Mitochondria
Plasmodium falciparum (protozoan) 6 5
Chlamydomonas reinhardtii (alga) 16 12
Mus musculus (mouse) 16
Homo sapiens (human) 17 37
Drosophila melanogaster (fruitfly) 19
Aspergillus nidulans (fungus) 33
Reclinomonas americiana (protozoan) 69 92
Saccharomyces cerevisiae (yeast) 75 35
Brassica oleracea (cabbage) 160
Arabidopsis thaliana (vetch) 367 52
Zea mays (corn) 570
Cucumis melo (melon) 2500

Chloroplast
Pisum sativum (pea) 120
Pryza sativa (rice) 136
Nico tabacum (tobacco) 156
Chlamydomonas reinhardtii (alga) 195

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