Comparative Genomics and the Evolution of Animal Diversity

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Chapter 19

• Comparative Genomics and the Evolution of Animal
  Diversity

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• The evolution of diversity among organisms
  is not due to the presence of different
  specialized genes.
• Rather,animal evolution depends on deploying
  the same set of genes in different ways.

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Most animal phyla fall into three major
groupsthe lophotrochozoans,ecdysozoans,and
deuterostomes.
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The figure shows the relationships among those
animals whose genomes have been sequenced to date
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• Where did the evolutionary diversity come from?
• How do genes acquire new patterns of expression
  during evolution?

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O U T L I N E

• Most Animals Have Essentially the Same Genes
• Three Ways Gene Expression is Changed during
  Evolution
• Experimental Manipulations that Alter Animal
  Morphology
• Morphology Changes in Crustaceans and Insects
• Genome Evolution and Human Origins

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Topic 1 Most Animal Have Essentially The Same
Genes
Comparison of the currently available
genomes reveals one particularly striking
featuredifferent animals share essentially the
same genes.
98 conservation in the protein coding genes
between human and chimp. The conservation
between human and mouse is over 80.
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Phylogenetic tree showing gene duplication of
the fibroblast growth factor genes(FGF)
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1-2 How Does Gene Duplication Give Rise to
Biological Diversity

• The increase in gene number seen in
  vertebrates is largely due to gene
  duplication.But how lead to increased
  morphological diversity?
• There are two models for how duplication genes
  can create diversity
• First,the duplication process creates genes
  encoding related proteins with slightly different
  activities.
• Second,duplication genes acquire new
  regulatory DNA sequences.

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Topic 2 Three Ways Gene Expression is
Changed Evolution
Changes in gene expression during evolution
depend on altering the activities of a special
class of regulatory genes,called pattern
determining genes. How changes in the
deployment or activities of these pattern
determining genes produce diversity during
evolution?
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There are three major strategies for altering
the activities of pattern determining genes.

• Changes in their expression profiles.
• Changes in the function of the encoded regulatory
  proteins .
• Changes in the enhancers that are regulatory and
  regulated by pattern determining proteins.

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FigSummary of the three strategies for altering
the roles of pattern determining genes.
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Topic 3 Experimental Manipulations that
alter Animal Morphology
How the morphology of the fruit fly can be
altered by manipulation the activities of
specific pattern determining genes? Then apply
these strategies to the interpretation of the
evolutionary diversification seen in different
groups of arthropods.
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3-1 Changes in Pax6 Expression Create Ectopic
Eyes
The most notorious pattern determining gene is
Pax6,which controls eye development in most or
all animals. Changes in the expression pattern
of the Pax6 gene are probably responsible for
some of the morphological diversity seen among
the eyes of different animals.
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Pax6 is normally expressed within developing
eyes. But when misexpressed in the wrong
tissues,Pax6 causes the development of extra eyes
in those tissues.
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Adult eye
Figure shows Misexpression of Pax6 and eye
formation in Drosophila. (a) Wild-type fly (b)
Abnormal leg with misplaced eye.The eye and legs
arise from imaginal disks in the larvae.
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3-2 Changes in Antp Expression Transform
Antennae into Legs

• A second Drosophila pattern determining
  gene, Antp(Antennapedia),controls the development
  of the middle segment of the thorax,the
  mesothorax,which produces a pair of legs that are
  morphologically distant from the forelegs and
  hindlegs.
• Antp encodes a homeodomain regulatory protein
  that is normally expressed in the mesothorax of
  developing embryo.
• The gene is not expressed,for example,in the
  developing head tissues.But a dominant Antp
  mutation,caused by a chromosome inversion, brings
  the Antp protein coding sequence under the
  control of a foreign regulatory DNA that
  mediates gene expressing in head
  tissues,including the antennae.

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A dominant mutation in the Antp gene results
in the homeotic transformation of antennae into
legs.
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3-3 Importance of Protein FunctionInterconver
sion of ƒtz and Antp

• Two related pattern determining genes in
  Drosophila,the segmentation gene ftz(fushi
  tarazu) and the homeotic gene Antp.
• The two encoded proteins are related and contain
  very similar DNA-binding domains(homeodomains)
• Antp contains a tetrapeptide sequence motif,
  YPWM,which mediates interactions with a
  ubiquitous regulatory protein called
  Exd(Extradenticle)
• In contrast, Ftz contains a pentapeptide
  sequence,LRALL,which mediates interactions with a
  different ubiquitous regulatory protein,FtzF1.

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FigureDuplication of ancestral gene leading to
Antp and ƒtz.
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3-4 Subtle Changes in an Enhancer Sequence can
Produce New Patterns of Gene Expression

• The third mechanism for evolutionary diversity
  is changes in the target enhancers that are
  regulated by pattern determining genes.This
  mechanism is nicely illustrated by the Dorsal
  regulatory gradient in the early fly embryo.
• Target enhancers that contain low-affinity
  Dorsal binding sites are expressed in the
  mesoderm,where there are high levels of the
  Dorsal gradient.
• Enhancers with high-affinity sites are expressed
  in neurogenic ectoderm,where there are
  intermediate and low levels of the gradient.

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• Single nucleotide substitutions that covert each
  site into an optimal Dorsal binding site cause
  the modified enhancer to be activated in a
  broader pattern.
• When combined with the two nucleotide
  substitutions that produce high-affinity Dorsal
  binding site,the modified enhancer now directs a
  broad pattern of gene expression in both the
  mesoderm and neurogenic ectoderm.
• A modified enhancer, containing optimal Dorsal
  sites,Twist activator sites,and Snail repressor
  is expressed only in the negurogenic ectoderm
  where there are low levels of the Dorsal
  gradient.

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FigureRegulation of transgene expression in the
early Drosophila embryo
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3-5 The Misexpression of Ubx Changes the
Morphology of the Fruit Fly
The analysis of Drosophila pattern
determining gene called Ubx illustrates all three
principles of evolutionary changenew patterns of
gene expression are produced by changing the Ubx
expression pattern,the encoded regulatory
protein,or its target enhancers. Ubx encodes
a homeodomain regulatory protein that controls
the development of the third thoracic segment,the
metathorax.And it specifically repress the
expression of genes that are acquired for the
development of mesothorax.
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In adult flies,the mesothorax contains a pair
of legs and wings,while the mesothorax contains a
pair of legs and halteres.
Ubx mutants cause the transformation of the
metathorax into a duplicated mesothorax.
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Misexpression of Ubx in the mesothorax results in
the loss of wings.
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• 3-6 Changes in Ubx Function Modifty the
  Morphology
• The Ubx protein can function as a
  transcriptional repressor that precludes the
  expression of Antp and other mesothoraxgenes in
  the developing metathorax.
• It is not currently known how Ubx functions as a
  repressor.However,the Ubx protein contains
  speific peptide sequences that recruit repression
  complexes.

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FigureChanging the regulatory activities of
the Ubx protein.
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• 3-7 Changes in Ubx Target Enhancers Can Alter
  Patterns of Gene Expression
• Ubx binds DNA as a Ubx-Exd dimer.
• Many homeotic regulatory proteins interact with
  Exd and bind a composite Exd-Hox recognition
  sequence.
• Exd binds to a half-site with the core
  sequence,TGAT,whereas Hox proteins such as Ubx
  bind an adjacent half-site with a different core
  consensus sequence,A-T-T/G-A/G.

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Interconversion of Labial and Ubx binding sites
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Topic 4 Morphological Changes In Crustaceans And
Insects
The first two mechanisms,changes in the
expression and function of pattern determining
genes,can account for changes in limb morphology
seen in certain crustaceans and insects. The
third mechanism,changes in regulatory
sequences,might provide an explanation for the
different patterns of wing development in fruit
flies and butterflies.
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4-1 Arthropods Are Remarkably diverse
Arthropods embrace five groupstrilobites(sadl
y extinct),hexapods(such as insects),crustacean
s(shrimp,lobsters,crabs,and so on),myriapods(centi
pedes and millipedes),and chelicerates(horseshoe
crabs,spiders,and scorpions).
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4-2 Changes in Ubx Expression Explain
Modifications in Limbs Among the Crustaceans

• Artemia belongs to an order of crustaceans known
  as branchiopods.
• A different order of crustaceans called
  isopods.Isopods contain swimming limbs on the
  second through eighth thoracic segments just like
  the branchiopods.
• The limbs on the first thoracic segment of
  isopods have been modified.They are smaller than
  the others and function as feeding limbs,which
  called maxillipeds

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Changing morphologies in two different groups
of crustaceans.
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Why Insects lack Abdominal Limbs?
The loss of abdominal limbs in insects is due to
functional changes in the Ubx regulatory protein.
Evolutionary changes in Ubx protein function
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What is the basis for this functional
difference between the two Ubx protein? It
turns out that the crustacean protein has a short
motif containing 29 amino acid residues that
block repression activity.When this sequence is
deleted, the crustacean Ubx protein is just as
effective as the fly protein at repressing Dll
gene expression.
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Comparison of Ubx in crustacean and in insects.
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4-4 Modification of Flight Limbs Might Arise
from the Evolution of Regulatory DNA Sequences
Ubx has dominated morphological change in
arthropods.
Approximately five to ten genes are repressed
by Ubx.These genes encode proteins that are
crucial for the growth and patterning of the
wings.
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Changes in the regulatory DNA of Ubx target
genes
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Topic 5 Genome Evolution and Human Origins
Consider Functional diversity among different
mammals. The genomes of mice and humans have
been sequenced and assembled,and their comparison
should shed light on our own human origins.
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5-1 Humans Contain Surprisingly Few Genes

• A variety of gene prediction programs are used to
  identify protein coding genes in whole-genome
  assemblies.
• Predicted genes are sometimes confirmed by
  independent tests-most frequently,the isolation
  of cDNAs corresponding to the encoded mRNAs.
• Therere numerous inaccuracies in the intro-exon
  structure of predicted genes due to the
  degeneracy and simplicity of the sequence signals
  required for splicing.

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• The human genome contains only 25000-30000
  protein coding genes.
• Organismal complexity is not correlated with gene
  number,but instead depends on the number of gene
  expression patters.

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5-2 The Human Genome Is very Similar to that
of the Mouse and Virtually Identical to the Chimp

• Mice and humans contain roughly the same number
  of genes-about 28000 protein coding genes.
• The chimp and human genomes are even more hightly
  conserved.
• Regulatory DNA evolve more rapidly than
  proteins.Perhaps the limited sequence divergence
  between chimps and humans is sufficient to alter
  the activities of several key regulatory DNAs.

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5-3 The Evolutionary Origins of Human Speech

• Alone humans possess the capacity for precise
  communication in the form of speech and written
  language.
• Speech depends on the precise coordination of
  the small muscles in our larynx and mouth.Reduced
  levels of a regulatory protein called FOXP2 cause
  severe defects in speech.

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• The FOXP2 gene was isolated in a variety of
  mammals,including mice,chimps,and orangutans.
• But in humans therere two amino acid residues at
  position 303 and 325 that are unique to
  humansthr to asn(T to N) at position 303 and asn
  to ser(N to S) at position 325.Perhaps these
  changes have altered the function of the human
  FOXP2 protein.
• Alternatively,changes in the expression pattern
  or changes in FOXP2 target genes might be
  responsible for the ability of FOXP2 to promote
  speech in humans.

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FIG 17 Summary of amino acid changes in the
FOXP2 proteins of mice and primates.
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FIG 18 Comparison of the FOXP2 gene sequences in
human,chimp, and mouse.
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5-4 How FOXP2 Fosters Speech in Humans

• The three mechanisms for changing the
  function of regulatory genes such as FOXP2.
• Changes in the FOXP2 expression pattern
• Changes in the FOXP2 amino acid sequence
• Changes in FOXP2 target genes
• Those are might explain the emergence as an
  important mediator of human speech.

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FIG 19 A scenario for the evolution of speech in
humans
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5-5 The Future of Comparative Genome Analysis

• Its possible to infer the function of roughly
  half of all predicted protein coding genes based
  solely on primary DNA sequence information.
• If a codon exists,which regulatory DNAs that
  mediate similar patterns of gene expression
  share,then it might be possible to infer both the
  timing and sites of gene expression by simply
  scanning the DNA sequences associated with any
  given gene.
• The continuing development of new computational
  methods and the availability of new genome
  assemblies offer exciting prospects for the use
  of comparative methods to reveal the mechanism of
  evolutionary diversity.

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