Previous IMEG Seminars and Abstracts:
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.
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
Lai et al., (2005). Control of cell proliferation and apoptosis by Mob as
tumor suppressor, Mats. Cell 120: 675-685.
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.
Park - Dept. of Biology
Title: Coding region
structural heterogeneity and turnover of transcription start sites contribute
to divergence in expression between duplicate genes
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
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.
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.
et al. (2005) Bayes empirical bayes
inference of amino acid sites under positive selection. Mol Biol Evol
et al. (1997) Small sample tests of
episodic adaptive evolution: a case study of primate lysozymes. Mol Biol
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
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
Title: The Tree of Life:
what does it really mean?
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
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
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
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.
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
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
Pilstrom L (2002)
The mysterious immunoglobulin light chain. Dev Comp Immunol
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.
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
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:
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:
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
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.
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:
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.
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]
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
NO IMEG SEMINAR~ THANKSGIVING
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
Chih-Hao Hsu - Dept. of Computer Science and Engineering - CANCELLED