Institute of Molecular
Evolutionary Genetics











Fall 2008


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Fall 2002




Speaker: Dr. Zhi-Chun Lai - Dept. of Biology

Title: Mob, Hippo and Warts - Control of tissue growth and organ size by an emerging tumor suppression pathway



Recent studies have lead to the discovery of a new tumor suppression pathway critical for growth inhibition during Drosophila development. Loss-of-function mutation in components of this pathway, such as mob, hippo, or warts, causes tumor formation. The hippo gene encodes a protein kinase and is required for activating both Warts protein kinase and Mats protein through phosphorylation.  Mats binds to and functions as a co-activator of Warts kinase. Our recent work has also shown that subcellular localization is critical for Warts activation. Once activated, Warts kinase phosphorylates growth-promoting Yorkie protein to prevent it from being translocated to the nucleus, where Yorkie acts as a transcription co-activator of Scalloped, a DNA-binding factor.  All of the pathway components are conserved in humans and similar regulatory mechanisms operate in human cells as well. Thus, dis-regulation of the hippo pathway might be involved in tumorigenesis in human cancer patients.


Zhao et al., (2008). TEAD mediates YAP dependent gene induction and growth control. Genes & Development. 22:1962-1971.

Zhao et al., (2007). Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes & Development 21:2747-2761.

Wei et al., (2007). Mob as tumor suppressor is activated by Hippo kinase in growth inhibition in Drosophila. The EMBO Journal 26:1772-1781.

Lai et al., (2005). Control of cell proliferation and apoptosis by Mob as tumor suppressor, Mats. Cell 120: 675-685.


Speaker: Dr. Norman Wickett - Dept. of Biology

Title: Comparative plastid genomics of the gametophyte dominated: examples from the bryophytes.


Bryophyte systematists have traditionally relied on a small number of readily accessible characters based on the architecture of the gametophyte and sporophyte. The combination of few characters and subjective categorization of character-states may account for the high levels of homoplasy revealed by recent phylogenetic analyses based on other sources of characters, primarily DNA sequence data. Families and orders of mosses are partially, to exclusively, defined by the architecture of the peristome. However, many taxa, presumably scattered across the moss tree of life lack a peristome. Inferences from chloroplast genome architecture have permitted us to resolve the precise affinities of some of these, leading, in some cases, to a transfer across ordinal boundaries. Plastid genome content may vary among lineages, which may illuminate informative patterns of molecular evolution or phylogeny. For example, the rpoA gene was lost at most twice during the radiation of mosses, whereas the cysA gene was lost multiple times throughout the evolution of liverworts. Architectural changes in the chloroplast genome (a 71kb inversion) of some mosses corroborated a weak phylogenetic signal carried by sequence data, supporting the establishment of a new order of morphologically reduced mosses. Plastid genome data may also help us understand the effects of dramatic shifts in life history. Aneura mirabilis is a non-photosynthetic liverwort that derives its fixed organic carbon from a host tree using a fungal endophyte as a physiological bridge between liverwort and host. We were able to show that many plastid genes underlying the photosynthetic apparatus are largely lost in structure and function.


Wickett NJ, Y Fan, PO Lewis & B Goffinet. 2008. Distribution and evolution of pseudogenes, gene losses and a gene rearrangement in pthe plastid genome of the non-photosynthetic liverwort, Aneura mirabilis (Metzgeriales, Jungermanniopsida). Journal ofMolecular Evolution 67: 111-122.


Wickett NJ, Y Zhang, SK Hansen, JM Roper, JV Kuehl, SA Plock, PG Wolf, CW dePamphilis, JL Boore & B Goffinet. 2008. Functional gene losses occur with minimal size reduction in the plastid genome of the parasitic liverwort Aneura mirabilis. Molecular Biology and Evolution 25(2): 393-401.


Goffinet B, NJ Wickett, O Werner, RM Ros, AJ Shaw & CJ Cox. 2007. Distribution and phylogenetic significance of the 71 kb inversion in the chloroplast genome in the Funariidae (Bryophyta). Annals of Botany 99: 747-753.


Speaker: Chungoo Park - Dept. of Biology

Title: Coding region structural heterogeneity and turnover of transcription start sites contribute to divergence in expression between duplicate genes


Gene expression divergence is one manifestation of functional differences between duplicate genes. Although rapid accumulation of expression divergence between duplicate gene copies has been observed, the driving mechanisms behind this phenomenon have not been explored in detail.

We examine which factors influence expression divergence between human duplicate genes, utilizing the latest genome-wide data sets. We conclude that the turnover of transcript start sites (TSSs) between duplicate genes occurs rapidly after gene duplication and that gene pairs with shared TSSs have significantly higher expression similarity than those without shared TSSs. Moreover, we find that most (55%) duplicate gene pairs do not retain the same coding sequence structure between the two duplicate copies and this also contributes to divergence in their expression. Furthermore, the proportion of aligned sequences in cis-regulatory regions between the two copies is positively correlated with expression similarity. Surprisingly, we find no effect of copy-specific transposable element insertions on the divergence of duplicate gene expression.

Our results suggest that turnover of TSSs, structural heterogeneity of coding sequences, and divergence of cis-regulatory regions between copies play a pivotal role in determining the expression divergence of duplicate genes.


1. Makova KD, Li WH: Divergence in the spatial pattern of gene expression between human duplicate genes. Genome research 2003, 13(7):1638-1645.
2. Li WH, Yang J, Gu X: Expression divergence between duplicate genes. Trends Genet 2005, 21(11):602-607.


Speaker: Dr. Masafumi Nozawa - Dept. of Biology

Title: Is positive selection really pervasive from recent genome sequence analysis?


Positive selection on amino-acid sequences can be inferred by comparing the rates of nonsynonymous and synonymous substitutions (dN/dS=w). The branch-site method has been popularized to detect positive selection. Using this method, many researchers have detected a considerable number of positively selected genes in genomes. However, the reliability of this method is largely unexplored. In this study, we have therefore conducted a computer simulation to test the reliability of the method in a comparison with the small-sample method based on Fisher’s exact test. The results showed that the branch-site method always gives a higher rate of false-positives than the small-sample method and the w value obtained by the branch-site method is not reliable at all. When positive selection was assigned in the computer simulation, a detection rate of positive selection was higher in the branch-site method than the small-sample method. Yet, the ratio of the detection rate to the false-positive rate was always higher in the small-sample method than in the branch-site method. These results suggest that the small-sample method is more reliable than the branch-site method to test the neutrality. Since the number of positively selected genes was very small when the small-sample test was used for the actual data, a substantial proportion of positively selected genes obtained by the branch-site method may be false-positives. Experimental confirmations are essential before getting conclusions about positive selection.


Yang et al. (2005) Bayes empirical bayes inference of amino acid sites under positive selection. Mol Biol Evol 22:1107-1118.


Zhang et al. (1997) Small sample tests of episodic adaptive evolution: a case study of primate lysozymes. Mol Biol Evol 14:1335-1338.


Bakewell et al. (2007) More genes underwent positive selection in chimpanzee evolution than in human evolution. Proc Natl Acad Sci USA 104:7489-7494.


Speaker: Erika Kvikstad - Dept. of Biology

Title: Ride the wavelet: Scale-specific dynamics of genomic contexts flanking small insertions and deletions



Insertions and deletions have received growing attention in the literature as a significant source of genome variation within and between species. Recent studies have highlighted the differences in rates and patterns of small insertions vs. deletions and revealed that these features are more different than previously expected. What remains unclear is how the local DNA sequence composition contributes to this heterogeneity, and how it can reveal clues to the relative contributions of the various mechanisms of indel mutagenesis. To investigate this, we analyzed sequence contexts of small insertions and deletions in the non-coding, non-repetitive portion of the human genome. Wavelet techniques that ascertain frequency fluctuations, and at multiple scales, were utilized to detect how small sequence motifs associated with mechanisms of DNA polymerase activity, topoisomerase cleavage, double-strand breaks and their repair, facilitate indel formation. Thus, we were able to ascertain the motifs and the scales at which significant patterns in their enrichment and fluctuation implied the participation of a molecular mechanism to insertion/deletion formation. In particular, recombination, via repair of paused replication forks, site-specific recombination and repair of non-B DNA structures, was revealed as a source of small indel mutagenesis., in addition to replication. Moreover, the wavelet analyses presented here confirm that observations of enrichment and significance of patterns are highly dependent on the scale of the interval analyzed and the coding vs. non-coding status of DNA sequences.



Ball, E., P. Stenson, S. Abeysinghe, M. Krawczak, D. Cooper, and N. Chuzhanova. 2005. Microdeletions and microinsertions causing human genetic disease: common mechanisms of mutagenesis and the role of local DNA sequence complexity. Human Mutation 26: 205-213.
Lio, P. 2003. Wavelets in bioinformatics and computational biology: state of art and perspectives. Bioinformatics 19: 2-9.
Kvikstad, E., S. Tyekucheva, F. Chiaromonte, and K. Makova. 2007. A macaque's-eye view of human insertions and deletions: differences in mechanisms. Public Library of Sciences Computational Biology 3: e176.


Speaker: MARKER LECTURE - Dr. W. Ford Doolittle - Biochem & Mole Biol Dalhousie University,  5:30 PM, 112 Borland Building

Title: The Tree of Life: what does it really mean?


Central to Darwin's contribution is the notion that evolution is a process of successive branchings, and thus that a single bifurcating Tree of Life can accurately represent natural relationships between organisms. Biologists have taken this as a fact and concentrated on reconstructing a universal Tree, using gene and more recently whole-genome sequence information. But it turns out that for bacteria and other microbes, transfer of genes across species lines (even over very great evolutionary distances) is sufficiently frequent that the relationships between their genomes are not tree-like. Doolittle argues that the Tree of Life is a hypothesis, not a fact, and that for prokaryotes (Bacteria and Archaea) it should be considered false, suggesting that scientists move to a more pluralistic perspective on natural relationships, just as they have adopted a pluralistic perspective on the forces driving evolutionary change.



Speaker: MARKER LECTURE - Dr. W. Ford Doolittle - Biochem & Mole Biol Dalhousie University, 4:00 PM, Berg Auditorium, 100 Life Sciences Building

Title: Entry-level metagenomics


Doolittle defines and defends the new science of metagenomics and illustrate application of metagenomic methods to four disparate projects/environments/systems currently or recently under investigation in his lab. These are (1) recombination and lateral gene transfer in hypersaline environments, (2) Thermotogas and mesotogas, (3) discovering freshwater microbial rhodopsins, and (4) integron metagenomics of contaminated sites.  He hopes to illustrate the value of mixing cultivated-organism-based, genome-based and metagenomic approaches in identifying and exploring interesting microbiology.



Speaker: Dr. James Marden - Dept. of Biology

Title: Molecules to metapopulations: genes that matter in a fragmented and dynamic landscape


We are examining the effect of metapopulation dynamics on evolution and spatial distribution of phenotypes and genotypes in the butterfly Melitaea cinxia in the Aland islands of Finland.  This butterfly metapopulation persists in a stochastic balance between extinction and colonization of discrete habitat patches.  New populations, particularly those with the lowest connectivity to existing populations, are founded by the most dispersive females.  Isolated opulations that have persisted for at least 5 yr tend to contain more sedentary females.  These traits are heritable and affect other aspects of life history, including fecundity.  We have found that genetic variation in a metabolic enzyme and alternative splicing of a muscle gene vary with population history and affect flight ability.  Using next-generation sequencing of cDNA, we have produced an annotated transcriptome and a custom Agilent microarray that we are using to test the hypothesis that global gene expression varies according to population history and connectivity.  Functional annotation of genes that differ in expression level between New and Old population females provides a hypothesis for a pathway, leading from an insertion/deletion mutation detected in the sequence data, to a cell regulatory pathway, flight metabolic capacity, dispersal ability and metapopulation processes.  These results shed new light on mechanisms and evolutionary processes occurring in populations that inhabit fragmented landscapes.



J. C. Vera, C.W. Wheat, H.W. Fescemyer, M.J. Frilander, D.L. Crawford, I. Hanski, J.H. Marden.  2008. Rapid transcriptome characterization for a non-model organism using 454 pyrosequencing. Molecular Ecology 17: 1636–1647.

Haag, C.R., Saastamoinen, M., Marden, J.H., and Hanski, I. 2005.  A candidate locus for variation in dispersal rate in a butterfly metapopulation.  Proceedings of the Royal Society of London B, 272, 2449-2456.

Hanski, I., Erälahti, C., Kankare, M., Ovaskainen, O. & Sirén, H. 2004. Variation in migration propensity among individuals maintained by landscape structure. Ecology Letters 7, 958-966.



Speaker: Dr. Sabyasachi Das - Dept. of Biology

Title: Evolutionary redefinition of immunoglobulin light chain isotypes in tetrapods



The phylogenetic relationships of immunoglobulin light chain (IGL) genes are difficult to resolve, because these genes are short and evolve relatively fast. Here, we classify the IGL sequences from 12 tetrapod species into three distinct groups, i.e., kappa ( ), lambda ( ), and sigma ( ) isotypes, using conserved amino acid residues, recombination signal sequences, and genomic organizations of IGL genes as cladistic markers. The distribution of the isotypes in tetrapods predicates three conclusions. First, the divergence of the , , and isotypes preceded the radiation of tetrapods. Second, the isotype was lost after the evolution of the amphibian lineage and before the emergence of the reptilian lineage. Third, the isotype was lost at least twice independently during tetrapod evolution, once in the bird lineage and second in the lineage of microbats. Conservation of the cladistic molecular markers for the , , and isotypes suggest that these markers are associated with the functional specialization of the three IGL isotypes. The genomic maps of IGL loci reveal multiple gene rearrangements that occurred in the evolution of tetrapod species. These rearrangements have resulted in interspecific variation of the genomic lengths of the IGL loci and the number and order of IGL constituent genes, but the overall organization of the IGL loci has not changed.


Pilstrom L (2002) The mysterious immunoglobulin light chain. Dev Comp Immunol 26:207-215.
Das S, Nikolaidis N, Klein J, Nei M (2008) Evolutionary redefinition of immunoglobulin light chain isotypes in tetrapods using molecular markers Proc Natl Acad Sci U S A 105:16647-16652.


Speaker: Dr. Kazuhiko Kawasaki - Dept. of Anthropology
Title: Duplication of SCPP genes and diversification of vertebrate mineralized tissues



The vertebrate tooth is covered with a hypermineralized tissue, enamel in most lobe-finned fish or enameloid in cartilaginous fish and ray-finned fish.  The evolutionary relationship among these two tissues, the hardest tissue in the body, and other mineralized tissues has long been a matter of controversy.  We have previously reported that specific combinations of secretory calcium-binding phosphoprotein (SCPP) genes are involved in mineralization of bone, dentin, enameloid, and enamel.  Thus, the early repertoire of SCPP genes would elucidate the evolutionary relationship across these tissues.  I have recently determined the repertoire of SCPP genes in various tetrapods and teleosts.  The result shows many lineage-specific genes and some widely conserved genes that originated in stem bony vertebrates or earlier.  Expression analysis of these genes reveals that some SCPP genes are used primarily in bone but also in dentin and other genes vice versa.  Dentin and enameloid initially use common SCPP genes in the matrix, but enameloid is subsequently hypermineralized.  Notably, enameloid and enamel use an orthologous SCPP gene in the hypermineralization process.  Thus, the hypermineralization machinery ancestral to both enameloid and enamel arose before the divergence of ray-finned fish and lobe-finned fish.  However, enamel employs specialized SCPPs as structuring proteins, not used in enameloid, demonstrating the divergence of enamel from enameloid.  These results show graded differences in mineralized dental tissues, and suggest that duplication of SCPP genes is correlated with incremental diversification of these tissues.



Kawasaki, K. and Weiss, K. M.  2003. Mineralized tissue and vertebrate evolution: The secretory calcium-binding phosphoprotein gene cluster.  Proc. Natl. Acad. Sci. USA. 100: 4060-4065.

Kawasaki, K., Suzuki, T., and Weiss, K. M.  2005. Phenogenetic drift in evolution: The changing genetic basis of vertebrate teeth.  Proc. Natl. Acad. Sci. USA. 102: 18063-18068.

Kawasaki, K. and Weiss, K. M.  2008. SCPP gene evolution and the mineralization continuum.  J. Dent. Res. (Crit. Rev. Oral Biol. Med.) 87: 520-531. 


Speaker: Dr. Nipam Patel - Investigator, Howard Hughes Medical Institute, University of California, Berkeley Dept. of Integrative Biology and Dept. of Molecular Cell Biology

Title: The Evolution of Animal Body Patterning



Genetic and molecular studies in model systems has given us great insights into the mechanisms that guide development.  I will describe how our knowledge of these mechanisms can be used to understand the developmental basis of morphological evolution, focusing on the evolution of appendage patterning within arthropods and snail shells within the molluscs.  Expanding developmental studies outside of standard models also reveals some very surprising differences such as unusual mechanisms for germline fate determination.


VanHook A., N.H. Patel. (2008) Crustaceans. Curr Biol. 18(13):R547-50.

Grande, C. and N.H. Patel (2008).  Nodal signaling is involved in left-right asymmetry in snails. Nature. in press.

Browne, W.E., and Patel, N.H. (2000) Molecular genetics of crustacean feeding appendage development and diversification. Semin. Cell. Dev. Biol. 11: 427-435.
 Averof, M. and N. H. Patel (1997). Crustacean appendage evolution associated with changes in Hox gene expression. Nature 388: 682-686.


Speaker: Dr. Eric Harvill - Dept. of Veterinary and Biomedical Science

Title: Relating Phylogeny, Phenotypes and -Omics to Reveal the Genetic Basis for the Virulence of the Bordetellae



The genomic sequence of three Bordetella species revealed substantially more shared "virulence factors" than are expressed by any individual strain or species, as well as a disproportionately high number of regulators.  We are currrently expanding by five the set of Bordetella genomes sequenced and annotated, and have investigated the differential expression of the shared set of "virulence factors" as it relates to the different virulence phenotypes of distinct but closely related lineages.  In a growing number of cases we have demonstrated that in vivo phenotypes can be related by expression microarrays to differential expression of specific factors, and to the specific genomic changes behind those differences.  A new project involving sequencing of 100s of B. pertussis genomes will extend and further inform this approach as well as identify the SNPs within the many lineages of B. pertussis worldwide, allowing us to distinguish and study the circulation of each.  We are currently seeking to expand our approaches to the analysis of these many genomes, and looking for new collaborators interested in using their analytical tools to examine these important and re-emerging pathogens.



Buboltz AM, Nicholson TL, Parette MR, Hester SE, Parkhill J, Harvill ET. Replacement of adenylate cyclase toxin in a lineage of Bordetella bronchiseptica. J Bacteriol. 2008 Aug;190(15):5502-11. Epub 2008 Jun 13.PMID: 18556799 [PubMed - indexed for MEDLINE]


Speaker: Matthew Heinicke - Dept. of Biology

Title: Diversification of the terraranan frogs, a vertebrate mega-radiation


The nearly 900 species of terraranans comprise fully 13% of known living amphibian species, and are the dominant amphibian group in the West Indies and Central and South America. We have performed molecular phylogenetic analyses including nearly 400 representative terraranan species to better understand the evolutionary history of the group. These analyses detect several strongly-supported clades, which do not correspond to traditional classifications. Clades within Terrarana are strongly linked with geography, with four separate radiations comprising the majority of species in Central America, the West Indies, northern South America, and Southeast Brazil, respectively. Molecular clock analyses show the terraranans to be a surprisingly young group. Analyses suggest the major West Indian and Central American groups arose in the mid-Cenozoic from South American ancestors, when no land bridges among these landmasses existed, while diversification within South America is correlated with the Andean progeny. The relationships of terraranans to other frogs have been poorly understood. Our phylogenetic analyses of 17 genes, including terraranans and other representative frog taxa, show that the closest relative of terraranans is an undescribed species from South America, for which we are describing a new family. The next closest relatives appear to be the marsupial frogs. Like the terraranans, the marsupial frogs are direct developers, suggesting that this reproductive mode evolved earlier than previously believed.


Heinicke, M. P., W. E. Duellman, and S. B. Hedges. 2007. Major Caribbean and Central American frog faunas originated by ancient oceanic dispersal. Proc. Natl. Acad. Sci. (USA) 104:10092-10097.
Hedges, S. B., W. E. Duellman, and M. P. Heinicke. 2008. New World direct-developing frogs (Anura: Terrarana): molecular phylogeny, classification, biogeography, and conservation. Zootaxa 1737:1–182.





Speaker: Dr. Blair Hedges - Dept. of Biology

Title: The Timetree of Life



Discussion on some new data and analyses concerning the relationships and timing of evolutionary divergences of organisms, from the origin of life to more recent divergences among vertebrates.  The work discussed will be from a synthesis in press: The Timetree of Life, S. B. Hedges and S. Kumar, Eds. (Oxford University Press, 2009).


No other references


Speaker: Chih-Hao Hsu - Dept. of Computer Science and Engineering - CANCELLED