Chapter 19 Comparative Genomics and the Evolution of Animal Diversity 周亚萍 生科1班 200331060105
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.
Most animal phyla fall into three major groups:the lophotrochozoans,ecdysozoans,and deuterostomes.
The figure shows the relationships among those animals whose genomes have been sequenced to date
Where did the evolutionary diversity come from? How do genes acquire new patterns of expression during evolution?
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
Topic 1 Most Animal Have Essentially The Same Genes Comparison of the currently available genomes reveals one particularly striking feature:different animals share essentially the same genes. 98%conservation in the protein coding genes between human and chimp. The conservation between human and mouse is over80%.
Phylogenetic tree showing gene duplication of the fibroblast growth factor genes(FGF)
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.
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,calledpattern determining genes. How changes in the deployment or activities of these pattern determining genes produce diversity during evolution?
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.
Fig:Summary of the three strategies for altering the roles of pattern determining genes.
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.
3-1 Changes in Pax6 Expression Create Ectopic Eyes The most notorious pattern determining gene is Pax6,which controls eyedevelopment 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.
Pax6 is normally expressed within developing eyes. But when misexpressed in the wrong tissues,Pax6 causes the development of extra eyes in those tissues.
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.
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.
A dominant mutation in the Antp gene results in the homeotic transformation of antennae into legs.
3-3 Importance of Protein Function:Interconversion of ƒtz and Antp • Two related pattern determining genes in Drosophila,the segmentation geneftz(fushi tarazu)and the homeotic gene Antp. • The two encoded proteins are related and contain very similar DNA-binding domains(homeodomains) • Antpcontains a tetrapeptide sequence motif, YPWM,which mediates interactions with a ubiquitous regulatory protein calledExd(Extradenticle) • In contrast,Ftzcontains a pentapeptide sequence,LRALL,which mediates interactions with a different ubiquitous regulatory protein,FtzF1.
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.
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.
Figure:Regulation of transgene expression in the early Drosophila embryo
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 change:new 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.
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.
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 “mesothorax”genes 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.
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.
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.
4-1 Arthropods Are Remarkably diverse Arthropods embrace five groups:trilobites(sadly extinct),hexapods(such as insects),crustaceans(shrimp,lobsters,crabs,and so on),myriapods(centipedes and millipedes),and chelicerates(horseshoe crabs,spiders,and scorpions).
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
Changing morphologies in two different groups of crustaceans.
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
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.
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.
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.
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. • There’re numerous inaccuracies in the intro-exon structure of predicted genes due to the degeneracy and simplicity of the sequence signals required for splicing.
The human genome contains only 25000-30000 protein coding genes. • Organismal complexity is not correlated with gene number,but instead depends onthe number of gene expression patters.
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.
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 calledFOXP2cause severe defects in speech.
The FOXP2 gene was isolated in a variety of mammals,including mice,chimps,and orangutans. • But in humans there’re two amino acid residues at position 303 and 325 that are unique to humans:thr 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.
FIG 17 Summary of amino acid changes in the FOXP2 proteins of mice and primates.
FIG 18 Comparison of the FOXP2 gene sequences in human,chimp, and mouse.
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.