Biology 340 Molecular Biology
Lectures 15 and 16
Eukaryotic Genomes
Reading: Chap. 9 Lodish et al.
Outline:
1. Gene organization prokaryotes vs. eukaryotes
2. Eukaryotic DNA sequences
3. Transposable elements
4. Chromosome structure
1. Gene organization
A. Gene=DNA coding region for RNA or protein plus signals for gene
expression.
B. In prokaryotes, many genes for proteins of related function lie next to each
other on the chromosome= operon. Introns are rare.
--example lac operon
C. In eukaryotes, most genes
--monocistronic
--interrupted by introns, esp. in higher eukaryotes, removed by splicing
--contain 5' control regions and transcription terminates downstream of a poly(A)
addition signal.
--alternate splicing enables multiple different proteins to be produced
2. Eukaryotic DNA sequences
Types of sequences in eukaryotic chromosomes
A. protein coding genes
--single copy genes
--gene families (duplicated and diverged genes)
Example:  globin: , , A, G,  -- five different functional genes encode
subunits of hemoglobin.
Hemoglobin: consists of 4 subunits, 2 alpha and 2 beta
 genes arose by duplication of ancestral gene followed by divergence
some genes evolve to be non-functional = pseudogenes
human  globin gene cluster (chromosome 11)
B. tandemly repeated genes
--rRNAs, tRNAs, histones
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C. Repetitive DNA
--simple sequence (example: AC repeat)
--mobile DNA elements (moderately repeated DNA)
--transposons
--retroposons
--LINES=long interspersed elements
--SINES=short interspersed elements
"C-value paradox" = Concept that we are not able to consistently predict DNA
content of an organism from its evolutionary complexity.
Mammalian DNA consists of 50-60% single copy DNA=genes, introns, some
spacer DNA; 25-40% moderately repeated DNA elements; 10-15% simple
sequence DNA, highly repetitive localized to centromeres and telomeres.
3. Transposable Elements
=mobile DNA elements
="selfish DNA"
=molecular parasites
Exist only to maintain themselves.
Discovered in 1940 by Barbara McClintock in corn. She later won the Nobel
prize for this work.
Mobile elements: Two categories (Fig. 9-10)
A. DNA transposons: replicate via a DNA intermediate.
Examples: Bacterial: IS elements and transposons. Transposons are larger
and typically contain an antibiotic resistance gene flanked by IS elements.
Eukaryotic: P elements of Drosophila and Ac and Ds elements of corn.
B. Retroposons: replicate via RNA intermediate which is copied by reverse
transcriptase into DNA.
Eukaryotic elements
Viral: Ty elements (yeast) and Copia elements (Drosophila)
Non-viral: LINE and SINE elements (mammals)
LINE elements: 600,000 in human genome (~15% of human DNA)
Need only one functional copy in genome for others to be able to transpose
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Alu elements (human)
~300 bp element present at 1 million sites in the human genome
(~10% of human DNA)
Retroposons appear to have no functional significance.
4. Chromosome organization
Bacterial chromosome:
--circular DNA chromosome
--naked DNA associated with + charged polyamines
--DNA is tightly supercoiled
Eukaryotic chromosomes:
--eukaryotic DNA exists in chromatin
--chromatin=DNA + histones + non-histone proteins
--five types of histone proteins: H1, H2A, H2B, H3, H4
contain many + charged amino acids which interact with - charged
phosphates of DNA
Chromatin structure: About 150 bp of DNA wrapped around histone core and 50
bp of DNA serves as linker to which H1 is bound.
Chromatin becomes more extended when genes are actively transcribed.
Histone acetylation is associated with more extended chromatin and active
genes.
Key components of chromosome structure:
1. Non-histone protein scaffold (Fig. 9-34)
2. Heterochromatin=regions of chromatin that remain condensed throughout the
cell cycle. Mostly this consists of repeated simple sequence DNA at the
centromere and telomeres.
3. ARS=Autonomously replicating sequences. Act as origins of replication.
Many ARS required to replicate a eukaryotic chromosome.
4. Centromere. Conserved DNA sequence elements (see Fig. 9-41).
5. Telomeres. Simple DNA sequence elements on the ends of chromosomes
produced by the enzyme telomerase. Required to maintain chromosome
integrity and stability.
Yeast Artificial Chromosomes: (YACs): vectors used for cloning larger
chromosomal regions such as human genomic fragments.
YACs consist of TEL (telomeres), CEN (a centromere), ARS (autonomously
replicating sequence) plus foreign DNA (50-1000 kb).
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