Download Transposable elements become useful genes

The Stability of the Genome
Duplication, Deletion, Transposition
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Duplication of DNA sequences
• Could result from unequal crossover
– chromosomes are not perfectly aligned during
meiosis
– One gets a duplication; the other gets a
deletion
– Process continues, to build tandem repeats
• After duplication, base substitutions
(variation)
• Multiple gene family members from one
ancestral copy - divergence required
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Figure 10.24
Evolution of globin genes
• Hemoglobin is tetramer: 4 globin chains
• Globin genes from different vertebrates have
common features
– All globins have 3 exons & 2 introns
• Globin-like proteins are different
– leghemoglobin from plants; muscle myoglobin
– 4 exons & 3 introns
– ancestral? (4 exons to 3 exons)
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Evolution of globin genes
• fusion of 2 exons (~800 million years ago)
• Some primitive fish have only one globin gene
• perhaps fish diverged before the first duplication
• First duplication formed a & b (~500 million yrs ago)
•
a & b separated transposition/translocation
• today's organization humans
– a-globin genes clustered on chromosome 16,
– b-globin genes clustered on chromosome 11
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Figure 10.26
Evolution of globin genes
• Hemoglobin made of 2 pairs of chains
– One pair always a-family; the other always b-family
– Combinations differ with stage of development
– embryonic, fetal, adult
• Clusters also contain pseudogenes
– have mutations that stop function
– evolutionary relics
– widespread in many gene families
– function unknown (junk?)
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Evolution of globin genes
• Parts of globin genes evolve at very different
rates
– DNA of coding regions is highly conserved
– Noncoding regions are much more variable
– Coding area changes are most frequently one
base substitutions
– Noncoding - often include additions & deletions
as well
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Evolution of gene families
• Evolving Sequence and Function
– Growth hormone & prolactin are pituitary
hormones
• Related amino acid sequences
• Evoke completely different responses from
target cells
– Number of changes only ROUGHLY
corresponds to time
– Redundant codons allow “silent” substitutions
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Transposons
• Described by Barbara McClintock (Cold Spring
Harbor, late 1940s)
– Nobel Prize – 1983
– Initially ignored: papers (and subject) complex
– Studied patterns & markings in leaf & kernel
coloration maize
– Noticed instability in markers in both germ line and
soma
– Concluded movement of genetic elements affecting
gene expression
– Defined terms: transposition and transposable
elements
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Transposons
• Eventually (late 1960s) verified transposons in bacteria
– Encode transposase enzyme
– Excision from donor site & insertion at target site
– bind to specific sequences (IR’s) ends of transposon
– complex binds to target DNA
– catalyzes integration
– Integration creates small duplication in target (DR’s)
– “Footprints” left behind when transposon excises
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
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Karp/CELL & MOLECULAR BIOLOGY 3E
Figure 10.28
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Figure 10.29
Transposons
• Eukaryotic genomes contain large numbers
of transposable elements
– ~40% of DNA in human cell nucleus from
transposable elements
– Vast majority are crippled by mutation or
suppressed
– they insert almost randomly within target DNA
• sometimes cause mutations in genes
• ~1 in 500 human mutations caused by
transposons
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Mechanisms of transposition are complex
• Some are excised from donor site and
inserted into target
– Example: mariner family of transposons
– Found throughout plant & animal kingdoms
• Some are replicated leaving donor site
unchanged (bacteria)
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Mechanisms of transposition are complex
• Often, transposition in eukaryotes involves RNA
intermediate
– DNA transcribed, producing an RNA
– Converted to DNA by reverse transcriptase
– dsDNA copy is integrated into target DNA site
– Retrotransposons sometimes have gene for RVTase
– Retroviruses, like the AIDS virus related to
retrotransposons
• Acquired envelope protein genes
• Or, loss of envolope gene could make transposon
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Figure 10.30
Mobile elements and evolution
• Most moderately repeated sequences of
genome are
– interspersed & arise by transposition
– 2 most common families: Alu & L1 families
– both transpose by means of RNA intermediates
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Mobile elements and evolution
• L1
– ~500,000 copies; ~15% of total nuclear DNA
– Vast majority of these are incomplete & defective
– Likely present in earliest eukaryotic cells (found
everywhere)
– Full length, human L1 sequence
• at least 6000 bp in length)
• encodes unique protein with 2 catalytic activities
• Endonuclease activity cleaves target DNA
• Reverse transcriptase activity makes DNA from RNA
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Mobile elements and evolution
• Alu
– roughly 1 million copies
– Family of short sequences ~300 bp in length
– Related to 7S RNA
• present in signal recognition particles
• found with membrane-bound ribosomes
– Alu origin: 7S RNA & reverse transcription?
– Amplification aided by L1 endonuclease?
– Seen only in higher primates
– First appearing ~60 million years ago
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Mobile elements and evolution
• Proposed functions of transposable elements
– No function - a genetic parasite
– Fuels evolution
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Support for evolutionary role
• Found as essential parts of regulatory regions
– Human parathyroid hormone gene expression
controlled, in part, by relics of transposable element
• Can clearly reorder genomes
– Domain shuffling using introns as breakpoints
• Transposable elements become useful genes
– Telomerase derived from reverse transcriptase?
– Enzymes involved in antibody gene rearrangement
are derived from transposase encoded by ancient
DNA transposon
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E
Support for evolutionary role
• Transposable (P) element of Drosophila
melanogaster
– T. H. Morgan's flies from 1900s devoid of the P
element
– All members of the wild species have it today
– Spread rapidly (80 years)
• Transmission likely mediated by parasites
Copyright, ©, 2002, John Wiley & Sons, Inc.,
Karp/CELL & MOLECULAR BIOLOGY 3E