Transcript Duplications create multigene families and gene superfamilies

PowerPoint to accompany
Genetics: From Genes to
Genomes
Fourth Edition
Leland H. Hartwell, Leroy Hood,
Michael L. Goldberg, Ann E. Reynolds,
and Lee M. Silver
Prepared by Mary A. Bedell
University of Georgia
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PART
VI
Beyond the Individual Gene and Genome
CHAPTER
Evolution at
the Molecular
Level
CHAPTER OUTLINE




20.1 The Origin of Life on Earth
20.2 The Evolution of Genomes
20.3 The Organization of Genomes
20.4 A Comprehensive Example: Rapid Evolution in the Immune Response and in HIV
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Charles Darwin's theory of evolution
"On the Origin of Species by Means of Natural Selection"
• Published in 1859, based on 5 years of collecting
specimens from around the globe
Three principles:
• Variation exists among individuals of a population
• Variant forms of traits can be inherited
• Some variant traits confer an increased chance of
surviving and reproducing
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The origin of life on earth
Self-replicating molecules may have led to the complexity of
cells
The first step in life had to fulfill three requirements:
• Encode information by variation of letters in strings of
a simple digital alphabet
• Fold in three dimensions to create molecules capable
of self-replication and other functions
• Expand the population of successful molecules
through selective self-replication
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The RNA world
1980s, Thomas Cech discovered ribozymes - RNA that can
catalyze chemical reactions
RNA satisfies all three requirements of
the first replicator: linear strings encode
information, folds into a 3-dimensional
molecular machine, reproduces itself
Intrinsic disadvantages of RNA
• Relatively unstable
• Limited capability for 3-dimensional
folding compared to proteins
• No record of intermediates between
an RNA world and cell complexities
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Fig 20.1
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Evolution of living organisms
4.5 billion yrs ago − coalescence of planet earth
4.2 billion yrs ago − emergence of informational RNA
3.7 billion yrs ago − life began
3.5 billion yrs ago − oldest fossilized cells (see Fig 20.2)
1.4 billion yrs ago − emergence of eukaryotes
• Symbiotic incorporation of single-celled organisms into
other single-celled organisms
• Complex compartmentalization of cell interior (nucleus)
1 billion yrs ago − ancestors of plants and animals diverged
0.57 billion yrs ago − explosive appearance of multicellular
animals (metazoans) and plants
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Living organisms evolved into three kingdoms
The length of the branches is proportional to the times of
species divergence
Fig 20.3
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The Burgess shale of southeastern
British Columbia
One of the most amazing finds in paleontology!
Enormous diversity in body plans – many are extinct but
some still exist
Punctuated evolution – short periods of explosive change
All basic body plans of metazoans are represented
Fig 20.4
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The evolution of humans
35 million yrs ago − humans arose from a common
ancestor to most contemporary primates
6 million yrs ago – divergence of humans and
chimpanzees from a common ancestor
Fig 20.5
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Similarities between chimps and humans
Genomes are 99% similar
Karyotypes are nearly the same (see Fig 12.11)
No significant differences in gene function
Differences between species may have been caused by only
a few thousand isolated genetic changes
Species-specific differences probably occurred because of
alterations in regulatory sequences
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DNA alterations form the basis of
genomic evolution
New mutations provide a continuous source of variation
Replacement of individual nucleotides in coding regions:
• Synonymous – substitutions have no effect on
encoded amino acid
• Nonsynonymous – substitutions cause change in
amino acid or premature termination codon
Order and types of transcription factor binding sites in gene
promoters can be altered
Mutations can be deleterious, neutral, or favorable
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Classification of mutations according to effect
Neutral mutations are not affected by the agents of selection
• Survive or disappear from a population by genetic drift
• Synonymous mutations can produce minute advantage or
disadvantage
 Availability of different tRNAs and tRNA-synthetases?
Deletions and insertions almost certainly have an effect
Mutations with only deleterious effects disappear because of negative
selection
Mutations with advantageous effects will increase in the population
because of positive selection
• May become fixed in the population
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Gene regulatory networks may dominate
developmental evolution
Sea urchins and sea stars diverged ~ 500 million yrs ago
But, they share some basic gene networks (Fig 20.6b)
Fig 20.6a
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Gene regulatory
networks in
sea urchins
and in sea stars
Rewiring of a gene
regulatory network
can encode enormous
phenotype change
Fig 20.6b
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An increase in genome size generally
correlates with evolution of complexity
Duplication and diversification of genomic regions
• Can occur at random throughout genome
• Sizes range from a few nucleotides to the entire
genome
• Can occur through transposition or unequal crossingover
• Either the original or copy of the gene can accumulate
mutations
Acquisition of repetitive sequences – can make up more
than 50% of a genome
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Transposition may occur through excising and
reinserting the DNA segment
Fig 20.7a
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Transposition events that produce duplications
Transposition through an RNA
intermediate
Transposition through a DNA
intermediate
Fig 20.7b
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Fig 20.7c
17
Transposition through
direct movement of a
DNA sequence
After transposition occurs in
a germ cell, the new copy of
the transposon may become
fixed in the next generation
Fig 20.8
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Duplications resulting from
unequal crossing- over
Also referred to as
"illegitimate recombination"
Mediated by sequence
similarity between related
sequences located close to
each other
After the initial duplication,
subsequent rounds of
unequal crossing over can
occur readily
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Fig 20.9
19
Duplicated genes can evolve into
pseudogenes or evolve new functions
Pseudogenes – nonfunctional genes that results from
random mutations in a duplicated gene
• Loss of regulatory function, substitutions at critical
amino acids, premature termination, frame-shift
mutation, altered splicing patterns
• Accumulate mutations at a fast pace
New functions can arise in a duplicated gene
• Random mutations provide selective advantage to the
organism
• The new gene usually has a novel pattern of
expression
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Evolutionary histories are diagrammed
in phylogenetic trees
Molecular clock – provides a good
estimate of time of divergence
because rate of evolution is
constant across all lineages
Phylogenetic tree illustrates
relatedness of homologous
gene or proteins
• Nodes are taxonomic units
• Branch lengths represent
time that has elapsed
Fig 20.10
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Four levels of gene duplication have fueled
evolution of complex genomes
At each level, diversification and selection can occur
• Exons duplicate or shuffle
• Entire genes duplicate to create multigene families
• Multigene families duplicate to produce gene
superfamilies
• Entire genome duplicates to double the number of
copies of every gene and gene families
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Duplications create
multigene families
and gene superfamilies
Hierarchical generation of
greater amounts of new
information at each level
Fig 20.11
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The basic structure of a gene
Fig 20.12
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Domains in antibody proteins
Discrete exons can
encode the structural
and functional
domains of a protein
Duplication of exons,
can create tandem
functional domains
Fig 20.13
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The tissue plasminogen activator gene evolved
from shuffling of three genes
New proteins with different combinations of functions can
be created by exon shuffling
Fig 20.14
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Duplications of entire gene can create
multigene families
Multigene family – set of genes descended by duplication
and diversification from one ancestral gene
Fig 20.15
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Unequal crossing over can expand and
contract gene numbers in multigene families
Fig 20.16
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Intergenic gene conversion can increase
variation in members of a multigene family
Alternative outcome to
unequal crossing-over
Allows transfer of
information from one
gene to another
Fig 20.17
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Increasing the number of alleles through
gene conversion
Major histocompatibility complex (MHC) of mice – a
pseudogene family was the reservoir of genetic information
to produce a dramatic increase in variation
Fig 20.18
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Concerted evolution can lead to
gene homogeneity
Fig 20.19
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Evolution of gene superfamilies
Gene superfamily – large set of related genes that is
divisible into smaller families
Genes in each family are more closely related to each other
than to other members of the superfamily
Repeated gene duplication events followed by divergence
Globin gene superfamily – three branches in all vertebrates
• Two multigene families (β-like genes and α-like genes) and a
single myoglobin gene
Hox gene superfamily – four branches in mice, only one in
Drosophila
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Evolution of the mouse globin superfamily
Fig 20.20
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Evolution of the Hox gene superfamily of
mouse and Drosophila
Fig 20.21
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Repetitive “nonfunctional” DNA families
constitute nearly one-half of the genome
Many repetitive nonfunctional DNA families consist of
retroviral elements that have integrated into the host
• Provirus can be active or inactive
Long INterspersed Elements – LINE family
• "Selfish DNA", encodes reverse transcriptase
• Very old family, exists in many organisms
• May have been source material for retroviruses
Short INterspersed Elements – SINE family (e.g. Alu element
in humans)
• Does not encode reverse transcriptase
• Evolved from small cellular RNAs
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Creation of a LINE gene family
Fig 20.22
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Creation of a SINE gene family
SINEs depend on availability of reverse transcriptase
encoded by other elements (LINEs or retroviruses)
Fig 20.23
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The potential selective advantage of
selfish elements
SINEs and LINEs have had profound impacts on wholegenome evolution
Catalyze unequal homologous crossover events
• These duplication events can initiate formation of
multigene families
Some evolved regulatory functions – can act as enhancers
or promoters
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Simple sequence repeats (SSRs)
Tandem, nonfunctional repeats scattered throughout
mammalian genomes
Vary in size of repeating units (2 – 100s of nucleotides)
Microsatellites, minisatellites, and macrosatellites
Very useful molecular markers for genome analysis and
genotyping (Chapter 11)
Highly susceptible to unequal crossing-over and are highly
polymorphic in size
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Centromeres and telomeres contain
many repeat sequences
Centromeres – tandem arrays of noncoding sequences that
interact with mitotic and meiotic spindle fibers
•e.g. Human alphoid DNA – 171 bp repeat that extends > 1 Mb on
either side of centromere in each chromosome
•Each repeat is < 200 bp in length
•Increase efficiency and/or accuracy of chromosome segregation
Telomeres – tandem arrays of noncoding sequences that
are at ends of all mammalian chromosomes
•Arrays are 5 – 10 kb in length
•Each repeat is 6 bp in length
•Essential role in maintaining chromosome length
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A comprehensive example: Rapid evolution in
the immune response and in HIV
Evolutionary battle at the molecular level between the AIDS
virus and cells of the immune system
After viral infection, virus-specific immune response ensues
that can destroy the pathogen
HIV has a high mutation rate and is able to diversity and
amplify itself via selection
Speed of viral evolution is faster than the immune response
Effective triple-drug therapies act to reduce the rate of viral
replication
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The immune response
Differentiated B cells secrete
antibodies that destroy or
neutralize antigens
Expanded numbers of
memory T cells and B cells
allow a rapid response to the
2nd encounter with an antigen
Fig 20.24
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