Chapter 19 Comparative Genomics and the Evolution of Animal Diversity

1
Chapter 19 Comparative Genomics and the Evolution
of Animal Diversity

• Most animals have essentially the same genes
• Three ways gene expression is changed during
  evolution
• Experimental manipulations that alter animal
  morphology
• Morphological changes in crustaceans (?????) and
  insects
• Genome evolution and human origins

2
Fig 19-1 summary of phyla (?) Phyla a basic type
of animal Bilaterians deuterosomes
???? lophotrochozoans ectysozoans
3

• Whole-genome sequence information is now
  available for both ecdysozoans (fruit fly,
  nematode worm) and deuterostomes (mouse, puffer
  fish, zebrafish).

4
Fig 19-2 phylogeny ?????of assembled genome
5
Most animals have essentially the same genes

• Pufferfish, mice, and humans-each contain about
  30,000 genes. With very few exceptions, about
  every human gene has a clear counterpart in the
  mouse genome.
• The increase in gene number in vertebrates is
  mainly due to duplications of genes already
  present in ecdysozoans, rather than the invention
  of entirely new genes.

6
Fig 19-3 phylogenetic tree showing gene
duplication of the fibroblast growth factor genes
(FGFs). Ciona FGFs orange 6 Vertebrate FGFs
black 22 Each gene in the sea squirt duplicated
into an average of four copies in vertebrates.
7

• How does gene duplication give rise to biological
  diversity?

• Gene duplications give rise to related proteins
  with slightly different functions through
  mutations
• Duplicated genes do not necessarily take on new
  functions, but instead take on new regulatory DNA
  sequences, and the genes are expressed in
  different patterns

8
Box 19-2 Duplication of globin genes produce new
expression patterns and diverse protein
functions.
9
Three ways gene expression is changed during
evolution

• Pattern determining genes cause the correct
  structure to develop, but in the wrong place,
  when they are misexpressed in development
• eg. Pax6
• The average animal genome contain about 1,000
  kinds of regulatory genes, and about 100 are
  pattern-determining genes

10
Three strategies for altering the activities of
pattern-determining genes

• Pattern-determining gene itself be expressed in
  a new pattern
• Protein encoded by a pattern-determining gene can
  acquire a new function
• Target gene of a pattern-determining gene acquire
  new regulatory DNA sequences

11
Fig 19-4 three strategies for altering the roles
of pattern determining genes
12
Experimental manipulations that alter animal
morphology
13
Change in Pax6 expression create ectopic eyes
Fig 19-5 Misexpression of Pax6 (also called ey)
and eye formation in Drosophilla.
14
(No Transcript)
15
Changes in Antp (Antennapedia) expression
transform antenna into legs
Fig 19-6 A dominant mutation in the Antp gene
results in the homeotic transformation of
antennae into legs
16
Importance of protein function interconversion
of ftz and antp
Figure 19-7 Duplication of ancestral gene leading
to Antp and ftz
17
Subtle changes in an enhancer sequence can
produce new patterns of gene expression
18
Fig 19-8 Regulation of transgene expression in
the early Drosophila
19
The misexpression of Ubx changes the morphology
of the fruit fly

• Ubx encodes a homeodomain regulatory protein
  that controls the development of the third
  thoracic segment, the metathorax
• Ubx represses Antp and restricts Antp expression
  to be in the second thoracic segment, the
  mesothorax.

20
Fig 19-9 Ubx mutants cause the transformation of
the metathorax into a duplicated mesothorax
Ubx represses Antp in the metathorax and
restricts the expression of Antp to mesothorax.
In Ubx mutants, Antp is expressed in both
mesothorax and metathorax, and therefore the
metathorax is transformed into a mesothorax.
21
Fig 19-10 Misexpression of Ubx in the mesothorax
results in the loss of wings
The Cbx mutation disrupts the regulatory region
of Ubx, causing its misexpression in the
mesothorax and results in its transformation into
the metathorax.
22
Changes in Ubx function modify the morphology of
fruit fly embryos

• Ubx protein can function as a transcriptional
  repressor that precludes the expression of Antp
  and other mesothorax genes in the developing
  metathorax.
• Conversion of Ubx into a transcriptional
  activator causes it to function like Antp and
  promote the development of mesothorax.

23
Fig 19-11 Changing the regulatory activities of
the Ubx protein.
24
Changes in Ubx target enhancers can alter
patterns of gene expression
Fig 19-12 Interconversion of Labial and Ubx
binding site
Lab is a Hox protein that controls the
development of anterior head structure.
25
Morphological changes in crustaceans and
insectsArthropods ????? are remarkably diverse

• Trilobites ??? (extinct)
• Hexapods ??? (such as insects)
• Crustaceans ??? (shrimp, lobster, crabs etc)
• Myriapods ??? (centipedes ??, millipedes ???)
• Chelicerates ?????? (horseshoe crabs, spiders,
  scorpions)

26
Changes in Ubx expression explain modifications
in limbs among the crustaceans
Fig 19-13 changing morphologies in two different
groups of crustaceans. In branchiopods Scr
expression is restricted to head regions where it
help promote development of feeding appendage.
In isopods, Ubx is missing in T1 and so Scr is
expressed in both head segment and T1. Swimming
limb in T1 is thus transformed into a feeding
appendage.
27

• During the divergence of branchiopods and
  isopods, the Ubx regulatory sequences changed in
  isopods.
• The Ubx gene is not expressed in T1, therefore
  Scr is expressed in T1 and cause the development
  of maxillipeds.

28
Why insects lack abdominal limbs?

• The loss of abdominal limbs in insects is due to
  functional changes in the Ubx regulatory protein.
  
• In insects, Ubx and abd-A repress the expression
  of Distalless (Dll) in first seven abdominal
  limbs.

29

• Fig 19-14 Evolutionary changes in Ubx protein
  function.
• Dll enhancer is normally activated as 3 spots in
  drosophila embryos.
• (b) Missexpression of Drosophila Ubx in these 3
  spots cause the reduction of Dll expression
• (c) Missexpression of artemia Ubx in the three
  spots does not decresase Dll expression,

30
Fig 19-15 Comparison of Ubx in crustaceans and in
insects.
31
Modifications of flight limbs might arise from
the evolution of regulatory DNA sequences
Fig 19-16 Changes in the regulaotry DNA od Ubx
target genes. The Ubx repressor is expressed in
the halteres of dipterans and hindwings of
lepidopterans.
32
Genome evolution and human origins

• Humans contains surprisingly few genes
• 25,000-30,000
• Organismal complexity is not correlated with gene
  number, but instead depends on the number of gene
  expression patterns.

33

• Nematodes
• gene number 20,000
• patterns of gene expression 30,000
• Drosophila
• gene number 14,000
• patterns of gene expression 50,000

34
The human genome is very similar to that of the
mouse and virtually identical to the chimp

• There are very few new genes in humans that are
  completely absent in mice.

35
The evolutionary origins of human speech

• 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. Afflicted
  individuals exhibit difficulties in articulation.
• Potential target genes of the FOXP2 regulatory
  proteins might encode neurotransmitters or other
  critical signals in the developing larynx.

36
Fig 19-17 summary of amino acid changes in the
FOXP2 proteins of mice and primates.
37
Fig 19-18 Comparisons of the FOXP2 gene sequences
in human, chimp, and mouse.
38
Fig 19-19 A scenario for the evolution of speech
in humans
39
The future of comparative genome analysis
Patterns of gene expressions
40
Expression of the yeast transcriptional activator
Gcn4 is controlled at the level of translation
Gcn4 a transcription activator that regulate the
genes that direct amino acid biosynthesis. Gcn4
itself is regulated at the translational level.
Low amino acid Gcn4 is translated High amino
acid Gcn4 is not translated.
41
uORF
mRNA encoding Gcn4 contains 4 small open reading
frames (uORF) upstream of the coding sequence.
Once uORF1 is translated, 50 of the small
subunit of ribosomes remain bound to the RNA and
resume scanning for the downstream AUG start
codon. However, before scanning the downstream
AUG, 40s subunit must bind eIF2 and initiating
tRNA fMET-tRNA.
42
(No Transcript)
43
Amino acid starvation eIF2 is phosphorylated
reduce the ribosome binding efficiency. Less
fMET-tRNA is available. Ribosome pass through
uORF2-4 before rebinding eIF2 and fMET-tRNA for
scanning.