Chapter 19 Comparative Genomics and the Evolution of Animal Diversity

✣ Author : 倪佩兰 ✣ Number: ✣生物科学类 1 ＞ Group8

OUTLINE  Three ways gene expression is changed during evolution.  Most animal have essentially the same genes.  Experimental manipulations that alter animal morphology.  Morphological changes in crustaceans and insects.  Genome evolution and human origins.

Preface of this chapter  Charles Darwin: all animals arose from a common ancestor.  There are 25 different animal phyla, but where did evolutionary diversity come?  Animal phyla includes :ecdysozoans,. lophotrochozoans, deuterostomes.  Different genomes offer the promise for diversity.

Figure 19-1 Summery of phyla

Figure 19-2 Phylogeny of assemble d genomes

Topic1: Most Animals Have Essentially the Same Genes  A striking factor: different animals have essentially the same genes (human, pufferfish and mice are similar in genome).  The genetic conversion seen among vertebrates extends to Ciona intestinalis.  Increase in gene number in vertebrates is due to the duplication of genes already present in the ecdysozoans rather than the invention of entirely new genes.

Figure 19-3 Phylogenetic tree show gene duplication of the fibroblast grouth factor genes

✰ How does gene duplication give rise to biological diversity? Two models for how duplicated genes can create diersity: ❶ An ancestral gene produce multiple genes via duplication,and the coding regions of the ew genes undergo mutation. ❷The duplicated genes do not take on new functions,but instead acquire new DNA sequences.

Box19-1 The structures of the genes coding the Gsb and Prd proteins

Box19-2 Duplication of β-Globin gene family in the evolution of vertebrates

Topic2:Three Ways Gene Expression Is Changed During Evolution ❶A given pattern determining gene can itself be expressed in a new pattern (this will cause those genes whose expression it controls to aquire new patterns of expression).( Figure19- 4a) ❷The regulatory protein encoded by a pattern determining gene can aquire new functions. ).( Figure19-4b) ❸Target pattern of a given pattern determining gene can acquire new regulatory DNA sequences, and thus come under the control of a different regulatory gene. ( Figure19-4c)

Figure19-4 Summery of the three strategies for altering the roles of pattern determining genes

Topic3:Experimental Manipulations That Alter Animal Morphology  The first pattern determining gene was identified in Drosophila in the Morgan Fly.Lab  During the past 20 years,a variety of manipulations have document the importance of several pattern determining genes in development.

ⅰ Changes in Pax6 expression create ectopic eyes  Pax6 Pax6 is the most notorious pattern determining gene.  Normally Pax6 express within developing eyes, but mistake appears, Pax6 causes the development of extra eyes.  Altered expression of Pax6 has been correlated with the formation of eye spot.  Pax6 genes from other animals also produce ectopic eyes when mixexpressed in Drosophila.. ⅱ

Figure19-5 Misexpression of Pax6 and eye formation in Drosophila

ⅱ Changes in Antp Expression Transform Antennae into Legs  Antp is a second Drosophila pattern determining gene which contril the development of the middle segment of the thorax,the mesothorax.  Antp encodes a homeodomain regulatory protein that is normally expressed in the mesothorax of the developing enbryo.  When misexpressed in the head, Antp causes a striking change: legs develop instead of antennae.

Figure19-6 A dominant mutation in the Antp geene results in the homeotic transformation of antennae into legs

ⅲ Importance of protein transform Antennae into legs  Pattern determining genes need not be expressed in different places to produce changes in morphology.  Example: two relared pattern deternmining genes in Drosophila :ftz and Antp.

Figure19-7 Duplication of ancestral gene leading to Antp and ftz

ⅳ Subtle Changes in an enhancer sequence can produce of gene expression  Enhancers with high-affinity sites are expressed in the neurogenic ectoderm.  The enhancer contains two low-affinity Dorsal binging sites,and is activate by high levels of the Dorsal gradient in ventral regions.  Dorsal functions synergisticaly with another transcripton factor Twist to activate gene expression in the neurogenic ectoderm.  So the enhancers can evolve quickly to create new patterns of gene expression.

Figure19-8 Regulation of transgene expression in the early Drosophila embryo

ⅴ The misexpression of Ubx changes the morphology of the fruit fly  New patterns of gene expression are produced by changing the Ubx expression pattern, or its target enhancers.  Ubx encodes a homeodomain regulatory protein  In figure 19-9b, Ubx mutants exhibit a spectacular phenotype: fly with four fully developed wings.  In figure 19-10, the Cbx mutation causes Ubx to be misexpressed in the mesothorax; and Ubx now represses the expression of Antp and some other genes.. As a result, in figure 19-10, Cbx mutant flies look like wingless ants.

Figure19-9 Ubx mutants cause the transformation of the metathorax into a duplicated mesothorax

Figure19-10 Misexpression of Ubx in the mesothorax results in the loss of wings

ⅵ Changes in Ubx modify the morphology of Fruit Fly embryos  Ubx functions as a repressor, and the Ubx protein contains specific sequences that recruit repression complexes.  Transgenic fly embryos have been create that either the Antp or Ubx protein coding sequence under the control of the hsp70 heat shock regulatory DNA.  Ubx normally functions as a repressor.

Figure19-11 Changing the regulatory activities of the Ubx protein

ⅶ Changes in Ubx target enhancers can alter patterns of gene expression  Ubx binds DNA as a Ubx-Exd dimer similarly to Antp.  Many homeotic regulatory proteins interact with Exd and binds a composite Exd-Hox recongnition sequence.  Ailering the function or expression of Ubx or its target enhancers changes patterning in the Drosophila embryos and adults.

Figure19-12 Interconve-rsion of labial and Ubx binding sites

Box Orgnization and expression of Hox genes in Drosophilla and in the mouse

Box Conservation of orgnization and expression of homeotic gene complexes in Drosophilla and in the mouse

Box Partial transformation of the first lumbar vertebra in a mutant mouse embryo

Topic4:Morphological Changes In Crustaceans And Insects  Three strategies for altering the activities of pattern determininggenes.  The first two,changes in the expression and function of pattern determining genes, explain changes in limb morphology seen in certain ctastaceans and insects.  The third, changes in regulatory sequences, explain different patterns of wing development in fruit flies and butterflies.

ⅰArthropods are remarkably diverse  Arthropods embrace five groups: trilobites, hexapods, crustaceans, myriapods, and chelicerates.  The success of the arthropods derives from their modular architecture.  These organisms are com[osed of a series of repeating body segments that can be modified in seemingly limitless ways.

ⅱ Changes in Ubx expression modifications in limbs among the crustaceans  Artemia,a group of crustaceans, is most studied.  Slightly different patterns of Ubx expression are observed in branchiopods and isopods.  Explanation: the Ubx regulatory DNA of isopods acquired mutations.

Figure Changing mophologi-es in two different groups of crustaceans

ⅲ Why insects lack abdominal limbs  The loss of abdominal limbs of insects is due to functional changes in the regulatory protein.  In crustaceans, there are high levers of both Ubx and Dll in all 11 thoracic segment.  The drosophila Ubx protein is functionally distinct from Ubx in crustacean. In contrast with fly, the crustacean protein has a short motif containing 29 amino acid residues that block repression activity.  Both the crustacean and fly proteins contain multiple repression genes. ⅲ

Figure19-14 Evolutionary changes in Ubx protein function

Figure19-15 Comparison of Ubx in crustaceans and insects

ⅳ Modification of flight limbs might arise from the evolution of regulatory DNA sequences  In Drosophila, Ubx is expressed in the developing halteres where it functions as a repressor of wing developed.  All members of dipterans contain a sinder pair of wings and a set of halteres.  The two olders diverged from a common ancestor more than 250 million years ago.  Reason for different wing morphologies: changes in the regulatory sequences of several Ubx targrt genes.

Figure19-16 Changes in the regulatory DNA of Ubx targrt genes

Box Distalless expression in various animal embryos

Box The expression of Dll and other pattern determining genes inthe eyespot ofβ.anynana

Topic5:Genome Evolution and Human Origins ⅰHumans contain surprisingly few genes  The human genome contain only protein coding genes.  The higher vertebrates contain sophisticated mechanisms for gene regulation in order to produce many patterns of gene expression.  Fruit flies is more complex than the worm from an increase in the number of gene expression patterns.

ⅱ The human genome is very similar to the mouse and the chimp  Mice and human contain roughly the same number of genes---about protein coding genes.  The chimp and human genomes are even more highly conserved.

ⅲ The evolutionary origins of human speech  One of the defining features of being human-- --speech.  Speech depends on the precise coordination of the small muscles in our larynx and mouth  Human ’ s FOXP2 protein is unique: T to N at position 303 and N to S at position 325.  Changes in the exprssion pattern of or changes in FOXP2 target genes might promote speech in humans. ⅲ

Figure19-17 Summery of amino acid changes in the FOX2 proteins of mice and primates

Figure19-18 Comparison of the FOX2 gene sequences in human, chimp and mouse

ⅳ How FOXP2 fosters speech in humans  Changes in the FOXP2 regulatory DNA might cause the gene to acquire a new pattern of gene expression in the human being.  Perhaps these changes have augmented the levels or timing of gene expression, so critical signals are active in the larynx when effected to language.  It is difficult to estimate the number of “ speech regulatory genes ” evolved in humans. ⅳ

Figure A scenario for the evolution of speech in humans

ⅴ The future of comparative genome analysis  It is impossible to infer the function of roughly half of all predicted protein coding genes based solely on primary DNA sequence information.  There is also a glaring limitation to infer the function of regulatory DNA from simple sequence inspection.  In the future it might e possible to identify changes in the expression profiles of homologous genes. ⅴ

 That is all for Chapter 19.  Thank you for appreciation!