Speaker and title of seminar
Speaker: Dr. Stephen W. Schaeffer- Department of
Title: Chromosomal Rearrangement during the Evolution of Drosophila
Abstract: Seven of the 12 Drosophila genomes that have
recently been sequenced provide an opportunity to understand the process
of chromosomal rearrangement because substantial changes in gene order
have taken place. This talk will focus on the method of linkage
chain analysis to infer the number of chromosomal inversion occurring on
various Drosophila lineages. This method examines the
information at conserved linkage group boundaries to link breakpoints
that have been involved in paracentric inversions. The distribution
of breakpoints within linkage chains provide a more accurate estimate of
the total number of inversions that have occurred down different Drosophila
lineages. The use of breakpoint information from outgroup species
allows the ancestral states of each inversion breakpoint to be determined
between a pair of species. The ancestral states can then be used to
infer the gene order of the common ancestral species. As an
example, a complete linkage chain analysis of the six chromosomes between
D. melanogaster and D. pseudoobscura will be presented. The
data show that while there is not a significant difference in the rate of
rearrangement between the two species, several chromosomes show
significant differences in inversion rates. Simulations of the
rearrangement process show that breakpoints are nonrandomly
re-used. I will briefly discuss the implications of genomic
comparison data between D. pseudoobscura and D. persimilis
to models of chromosomal speciation.
S., Y. LIU, B. R. BETTENCOURT, P. HRADECKY, S. LETOVSKY, R. NIELSEN, K.
THORNTON, M. A. TODD, R. CHEN, R. P. MEISEL, O. COURONNE, S. HUA, M. A.
SMITH, H. J. BUSSEMAKER, M. F. V. BATENBURG, S. L. HOWELLS, S. E.
SCHERER, E. SODERGREN, B. B. MATTHEWS, M. A. CROSBY, A. J. SCHROEDER, D.
ORTIZ-BARRIENTOS, C. M. RIVES, M. L. METZKER, D. M. MUZNY, G. SCOTT, D.
STEFFEN, D. A. WHEELER, K. C. WORLEY, P. HAVLAK, K. J. DURBIN, A. EAGAN,
R. GILL, J. HUME, M. B. MORGAN, Y. HUANG, L. WALDRON, D. VERDUZCO, K. P.
BLANKENBURG, H. ROBERTSON, I. DUBCHAK, M. A. F. NOOR, W. W. ANDERSON, K.
WHITE, A. G. CLARK, S. W. SCHAEFFER, W. M. GELBART, G. WEINSTOCK and R.
A. GIBBS, 2005 Comparative genome sequencing of Drosophila
pseudoobscura: Chromosomal, gene and cis-element
evolution. Genome Res. 15: 1-18.
NOOR, M. A., K. L.
GRAMS, L. A. BERTUCCI and J. REILAND, 2001 Chromosomal inversions and the
reproductive isolation of species. Proc. Natl. Acad. Sci. USA 98:
PEVZNER, P., and
G. TESLER, 2003 Human and mouse genomic sequences reveal extensive
breakpoint reuse in mammalian evolution. Proc. Natl. Acad. Sci. USA 100:
D., and P. TRINH, 2005 Chromosomal breakpoint reuse in genome sequence
rearrangement. J Comput Biol 12: 812-821.
Mark Shriver- Department of Anthropology
Title: The Genetic Architecture of Normal Variation in Human
Pigmentation: An Evolutionary
Perspective and Model
Abstract: Skin pigmentation varies substantially across human
populations in a manner largely coincident with ultraviolet radiation
intensity. This observation suggests that natural selection in response
to sunlight is a major force in accounting for pigmentation variability.
We review recent progress in identifying the genes controlling this
variation with a particular focus on the trait's evolutionary past and
the potential role of testing for signatures of selection in aiding the
discovery of functionally important genes. We have analyzed SNP data from
the International HapMap project in 77 pigmentation candidate genes for
such signatures. Based on these results and other similar work, we
provide a tentative three population model (West Africa, East Asia and
North Europe) of the evolutionary-genetic architecture of human pigmentation.
These results suggest a complex evolutionary history with selection
acting on different gene targets at different times and places in the
human past. Some candidate genes may have been selected in the ancestral
human population, others in the 'out of Africa' proto European-Asian
population, while most appear
to have selectively evolved solely in either Europeans or East Asians
separately despite the pigmentation similarities between these two
populations. Selection signatures can
provide important clues to aid
gene discovery. However, these should be viewed as complements, rather
than replacements of, functional studies including linkage and
association analyses, which can directly
refine our understanding of
STILL IN PRESS
Speaker: Dr. Jamie Blair- Plant Pathology -
Speaker: Dr. Helen Piontkivska- Department of
Biology -Kent State University
Title: "Host-pathogen interactions and sequence changes:
evolution of CTL and
epitopes in Human Immunodeficiency Virus (HIV-1)"
Abstract: In human immunodeficiency virus (HIV), mutations
that escape from cytotoxic T-lymphocyte (CTL) recognition have been
documented, and sequence analyses have provided indirect support for the
hypothesis that natural selection has favored CTL escape mutants within
an infected host. Similarly, neutralization of virus particles by
antibodies may also be contributing factor shaping the evolution of the
virus. However, the relative contribution of these two aspects of the
host immune response to selection on proteins of HIV-1 and related
viruses remains unclear. Our analyses of sequence data from the nine
protein-coding genes of HIV-1 showed striking differences in evolutionary
pattern between epitopes for host neutralizing antibodies (Ab) and
epitopes for CTL. Our results showed that the greatest median amino
acid residue diversity was seen at sites that formed part of Ab epitopes,
but not of CTL epitopes. By contrast, sites belonging to CTL epitopes but
not to Ab epitopes showed reduced median amino acid sequence diversity
not only in comparison to sites in Ab epitopes but also in comparison to
non-epitope sites. Further, Ab epitopes that did not overlap CTL epitopes
showed the highest frequency of comparisons in which the rate of
nonsynonymous (amino acid-altering) nucleotide substitution exceeded that
of synonymous nucleotide substitution, supporting the hypothesis that
much of the diversity at Ab epitopes results from positive selection
exerted by the host immune system. Though less frequent than that at Ab
epitopes, there was evidence of such selection at certain CTL epitopes as
well; and amino acid differences between sister pairs of sequences in CTL
epitopes were more likely to be convergent than those in Ab epitopes. The
pattern seen at CTL epitopes may represent the result of conflicting
pressures favoring conservation of the amino acid sequence for functional
reasons and amino acid replacements for reasons of CTL escape.
Speaker: Dr. Cooduvalli
Shashikant ~ Dairy and Animal Science Depart.
cis-regulatory analysis of a vertebrate Homeobox gene"
Abstract: The Hoxc8 early enhancer is a 200 bp
cis-regulatory region that controls initiation and establishment phase of
Hoxc8 expression during mouse embryonic development.
The Hoxc8 early enhancer comprises nearly a dozen elements
identified by comparative studies and mutational analysis in transgenic
mouse embryos. Comparative study shows a remarkably plasticity in
the Hoxc8 early enhancer activity. Species specific variation in
its sequence and elemental composition is reflected in differences in
their enhancer activities when assayed in transgenic mouse embryos.
The Hoxc8 early enhancer determines reporter gene expression by
two distinct mechanisms. One that determines tissue-specific
expression and a second determines the anterior extent of
expression. Transcription factors that are likely to regulate Hoxc8
expression include members of the Cdx, forkhead, Lef1/Tcf, Smad
and Hox families. Among these, Cdx2 is a strong
candidate to regulate Hoxc8 early enhancer activity. Cdx2
protein can bind to two distinct elements within the enhancer. Its
spatiotemporal expression pattern is consistent with the early phase of Hoxc8
expression. Comparison of Hoxc8 and Cdx2 regulation
suggests that they both respond to posteriorizing signals. Furthermore,
cis-regulatory analysis of Cdx2 reveals the presence of
positive-negative regulatory elements that control Cdx2
expression. Taken together these studies will present a model for a
posterior determination mechanism active during mouse embryonic
Bolanowski, S. Anand, and S.M. Anderson. Comparisons of diverged
vertebrate Hoxc8 early enhancer activities reveal modification of
regulatory interactions at conserved cis-acting elements Submitted.
W.C.H. and C.S. Shashikant. Evidence for positive and
negative regulation of the mouse Cdx2 gene. Submitted.
Shashikant C., S.A. Bolanowski, J.
Danke, and C.T. Amemiya. Hoxc8 early enhancer of the Indonesian
coelacanth, Latimeria menadoensis. J.Exp.Zool.
Mol.Dev.Evol. 302, 557-563, 2004.
Wang, C.H.W., S. Anand, D.R. Powell, A.B.
Pawashe, C.T. Amimiya, and C.S. Shashikant. Comparative
cis-regulatory analysis identify new elements of the mouse Hoxc8 early
enhancer. J.Exp.Zool. Mol.Dev.Evol. 302, 436-445, 2004.
Speaker: Dr. Kazuhiko Kawasaki - Department of
Title: Gene duplication and the evolution of vertebrate
Abstract: The mineralized skeleton is a critical innovation
that evolved early in vertebrate history. The tissues found in
dermal skeletons of ancient vertebrates are similar to the dental tissues
of modern vertebrates; both consist of a highly mineralized surface hard
tissue, enamel or enameloid, more resilient body dentin, and basal
bone. These tissues all form on distinct sets or compositions of
protein matrix. Many genes coding these proteins are evolutionarily
related and form the secretory calcium-binding protein (SCPP) gene
family. We hypothesize here the duplication histories of these SCPP
genes, and their common ancestors, SPARC and SPARCL1.
At around the same time that Paleozoic jawless vertebrates first evolved
mineralized skeleton, SPARCL1 arose from SPARC by whole genome
duplication. Then both before and after the split of ray-finned
fish and lobe-finned fish, tandem gene duplication created two types of
SCPP genes, each residing on the opposite side of SPARCL1 on the
same chromosome. One type of these genes was subsequently used in
surface tissue and the other in body tissue. In the tetrapod
lineage after the divergence from amphibians, these two types of SCPP
genes were separated by intrachromosomal rearrangement.
Subsequently, SCPP genes were co-opted for use by milk, saliva, and
eggshell. While new SCPP genes arose by duplication, some old genes
were eliminated from the genome. As a consequence of this
birth-and-death process, phenogenetic drift can occur: while mineralized
skeleton is maintained by natural selection, the underlying genetic basis
has drifted. The different genes used for mineralized tissues may
partly explain the variation of ancient mineralized tissues. Many
SCPP genes present in our genome today arose as redundant genes that survived
and diversified through the adaptive evolution of vertebrate
Kawasaki, K. and Weiss, K. M. Evolutionary genetics
of tissue mineralization: the origin and evolution of the secretory
calcium-binding phosphoprotein family. J. Exp. Zool. (Mol. Dev.
Evol.) 306B, 295-316, 2006.
Kawasaki, K., Suzuki,
T., and Weiss, K. M. Phenogenetic drift in evolution: the changing
genetic basis of vertebrate teeth. Proc. Natl.
Acad. Sci. USA.
102, 18063-18068, 2005.
Suzuki, T., and Weiss, K. M. Genetic basis for the evolution of
vertebrate mineralized tissue. Proc. Natl. Acad. Sci. USA.
101, 11356-11361, 2004.
K. and Weiss, K. M. Mineralized tissue and vertebrate evolution:
The secretory calcium-binding phosphoprotein gene cluster. Proc.
Natl. Acad. Sci. USA. 100, 4060-4065, 2003.
Speaker: Dr. Paula McSteen - Department
and hormonal regulation of inflorescence development in maize
Abstract: Unlike animals,
which make organs during embryogenesis, plants make organs throughout
their lifetime through the action of meristems. My lab focuses on
axillary meristems, which give rise to branches and flowers and therefore
play a fundamental role in plant architecture and reproduction. We aim to
understand how axillary meristems initiate using maize which is a model
system as it produces multiple types of axillary meristem in the
We have shown that auxin (a plant growth hormone) is required for
axillary meristem initiation in maize as treatment of plants with
inhibitors of auxin transport blocks initiation of axillary meristems.
The phenotype of plants treated with auxin transport inhibitors bears
striking resemblance to a large class of mutants in maize, called “barren
inflorescence”. We have taken a genetic approach to identify the genes
regulating auxin transport and perception by characterizing and cloning
the mutants in this class. One of these mutants is barren
inflorescence2 (bif2) which makes fewer branches, spikelets
and ear shoots due to defects in the initiation of axillary meristems.
The bif2 gene encodes a serine/threonine protein kinase which is
conserved in monocots and dicots. We are identifying additional
genes required for axillary meristem initiation by identifying proteins
that interact with BIF2. One of the proteins BIF2 interacts with and
phosphorylates is a transcription factor which is specific to monocots.
Therefore, although bif2 sequence and expression are conserved
between monocots and dicots, at least one of its putative downstream
targets may have diverged.
P. McSteen (2006) Branching out: The ramosa
pathway and the evolution of grass inflorescence morphology. Plant
Cell, 18: 518-522.
P. McSteen, O. Leyser (2005) Shoot
branching. Annual Review of Plant Biology, 56: 353-374.
Speaker: Kerr Wall - Department
Ultrahigh-throughput transcriptome tagging using pyrosequencing
Abstract: Over the last
year, pyrosequencing technology has been used to sequence
microbial and organelle
genomes, as well as small RNA libraries. A first
study has recently been
reported using this same technology to sequence cDNA
libraries. We report results
from several plates of pyrosequenced
transcripts from a model plant
species, Arabidopsis thaliana, and a
non-model basal eudicot,
Eschscholzia californica (California poppy). We
also discuss the implications
of this new technology for transcriptome
sequencing as well as the
advantages and disadvantages over traditional
References: Margulies et al (2005). Genome sequencing in
picolitre reactors. Nature. Sep
Bainbridge et al (2006).
Analysis of the prostate cancer cell line LNCaP
transcriptome using a
sequencing-by-synthesis approach. BMC Genomics. Sep
Moore et al (2006). Rapid and
accurate pyrosequencing of angiosperm plastid
genomes. BMC Plant Biol. Aug
Goldberg et al (2006). A
Sanger/pyrosequencing hybrid approach for the
generation of high-quality
draft assemblies of marine microbial genomes.
PNAS. Jul 25;103(30):11240-5.
Poinar et al (2006)
Metagenomics to paleogenomics: large-scale sequencing of
mammoth DNA. Science. Jan
Lu C et al (2006).
MicroRNAs and other small RNAs enriched in the
Arabidopsis RNA-dependent RNA
polymerase-2 mutant. Genome Res.
Veronica Hinman- Department of Biology, Carnegie Mellon University
Title: Regulatory Gene Network Evolution in
Abstract: We are
undertaking an evolutionary comparison of the gene regulatory network
(GRN) architectures that control specification in sea urchin and sea star
embryos. The extensive analysis of a GRN in sea urchins has
provided a unique opportunity for a comparative investigation to
elucidate mechanism of evolution at this level. We would like to
answer questions such as, which features of a regulatory network are
conserved, how are changes incorporated into a GRN, and how do these
changes relate to the evolution of morphology? The sea star Asterina
miniata has been developed as an ideal experimental model for this
analysis. Gametes are readily available and gene transfer and
perturbation of gene products have been performed. Sea stars last
shared a common ancestor with sea urchins around 500 million years ago,
in the Upper Cambrian. They appear to be at an ideal evolutionary
distance for meaningful comparisons since they share many conserved
aspects in their development and yet there exist specific morphological
We have previously shown that a common
developmental feature of sea star and sea urchin GRNs is the use of an
orthologous three gene positive regulatory feedback loop that serves to
‘lock down’ gene expression required for the specification of the
endoderm and thus to drive development forward. The conservation of
this feature across the immense period of evolutionary time such as
separates these echinoderms demonstrates the indispensable nature of this
process in their development. Several differences were also noted
in the GRN architecture. For example, tbrain (tbr) is
incorporated into the endomesoderm-specification network in the sea star
while it is involved in skeletal lineage specification in sea urchins.
The comparative GRN analysis has been continued
by asking how (in terms of GRN reorganization) tbr has been
co-opted for use in skeletogenesis in sea urchins. In this analysis
it was shown that the otx gene, although conserved in expression
and function, is regulated by Tbr in the sea star but not the sea urchin.
As a logical extension of this work, an extensive comparison of the
cis regulatory control module of the otx gene in the two
taxa was performed. We are able to demonstrate how the evolution of
function of the tbr gene is encoded in the cis regulatory
module of a target gene. These new data will be discussed.
Larroux, C., Fahey, B., Liubicich, D., Hinman, V. F., Gauthier,
M., Gongora, M., Green, K., Worheide, G., Leys, S. P. and Degnan, B. M.
(2006)Developmental expression of
transcription factor genes in a demosponge: insights into the origin of
metazoan multicellularity. Evol. Dev. 8(2):150-173.
Hinman, V. F., and Davidson, E. H. (2005)Expression of AmHNF6, a sea star orthologues of a
transcription factor with multiple distinct roles in sea urchin
development. Gene Expr Patterns. 5:381-386.
Hinman, V. F.,
Nguyen, A. T., Cameron, R. A. and Davidson, E. H. (2003).
Developmental gene regulatory network architecture across 500 million
years of echinoderm evolution. Proc Natl Acad Sci U S A 100,
Masafumi Nozawa - Department of Biology
stability of the number and the repertoire of olfactory receptor genes in
Abstract: Olfactory receptor (OR) genes play an important
role in olfaction and are essential for animals to find desirable items
and to avoid dangers. We have identified all OR genes in the draft
genome sequences of 12 Drosophila species by bioinformatic methods
and investigated their evolutionary dynamics using phylogenetic
analysis. The results have shown that there have been frequent gene
gain and loss events during the Drosophila evolution, suggesting
birth-and-death evolution. Many recent gene duplication events
occurred in tandem, indicating that unequal crossing over would be a
major mechanism for gene duplication. On the other hand,
chromosomal rearrangements and translocations have contributed to
establish the genome-wide distribution of OR genes, since the chromosomal
positions of orthologous genes were substantially different among
distantly related species. In spite of these gene gain and loss
events, all species examined have a similar number (51-66 genes) and
repertoire of functional OR genes. Estimating the numbers of OR
genes in ancestors for these species, we found that the ancestral species
also had similar numbers of OR genes compared to the extant
species. In addition, all clades defined in a phylogenetic tree
already existed in the ancestral species. These results suggest
that the number and the repertoire of OR genes have been stable during
the Drosophila evolution, which is in contrast to the evolutionary
dynamics of the mammalian OR genes. Mechanisms that keep the number
and the repertoire of Drosophila OR genes small and stable will be
Y., and M. Nei. 2005. Evolutionary dynamics of olfactory receptor genes
in fishes and tetrapods. Proc. Natl. Acad. Sci. USA 102: 6039-6044.
H. M., and K. W. Wanner. 2006. The chemoreceptor superfamily in the honey
bee Apis mellifera: expansion of the odorant, but not gustatory,
receptor family. Genome Res. 16 In press.
Hartl- Higgins Professor of Biology Harvard University -Marker Lecture
8:00 PM 104 Keller Bldg.
odds against the less fit: Evidence for positive selection in protein
Abstract: Short description: Analysis of DNA sequence
variation within and between species confirms that many amino acid
polymorphisms are deleterious, that some deleterious polymorphisms can
become fixed, but that the majority of amino acid replacements are
probably driven by weak positive selection. Some explanations are
Hartl- Higgins Professor of Biology Harvard University- Marker Lecture
12:00 PM 117 HUB Auditorium
Title: Transcriptional variation
and plasticity in the yeast genome.
plasticity refers to changes in the level of transcription that take
place in response to changes in the environment. Although a great deal is
known about the transcriptome of laboratory yeast (S. cerevisiae)
and its response to environmental changes, relatively little is known
about either transcriptional plasticity or GEI for transcriptional
plasticity among genetically diverse natural isolates. We have studied
genome-wide patterns of gene expression in six natural isolates grown in
each of four different environments representing a continuum of rich and
poor nutritional conditions. We have also identified a single-gene
difference segregating in natural populations that is associated with
increase in transcription of about 150 genes and a decrease in
transcription of about 200 genes. Evidence is presented that the
polymorphism responsible for these manifold physiological effects is in a
gene that encodes a major sensor of the external nutritional environment.
Speaker: THANKSGIVING HOLIDAY BREAK~ NO SEMINAR
Yogeshwar Kelkar - Department of Biology
Title: Factors affecting microsatellite mutability inferred
from human-chimpanzee genomic alignments
tandemly repeated nucleotide sequences of small motifs (1-6 bp), are
ubiquitous in eukaryotic genomes. They undergo rapid change in their
length due to insertion or deletion of one or multiple basic repeat
units. Though these repeats are simple, their mutational mechanism is not
very well understood. Microsatellite mutations take place at very high
rates, as high as 10-4 to 10-3 mutational events per cell per replication
in humans. Some of these repeats are very unstable and responsible for
more than 40 known neurological, neurodegenerative, and neuromuscular
disorders; though only certain trinucleotide repeats are responsible for
most of these disorders.
It is now widely accepted that number of repeats in a microsatellite is
an important determinant of mutation rate in the sense that longer
microsatellites mutate faster, although there is no clear consensus over
the exact manner in which length affects microsatellites. Also, the motif
that makes up a microsatellite determines mutability of microsatellite to
a large extent.
There is a lot of variation in mutability of microsatellites. It has been
experimentally shown that two similar microsatellites can mutate at very
different rates if the context of their flanking sequences is changed.
Clearly, microsatellite mutation process is a function of inherent
sequence properties, local as well as of large-scale genomic factors. A
comprehensive model that incorporates all known factors affecting
microsatellite mutability is needed. Here we are trying to correlate
various local genomic factors around microsatellites, with the mutability
of microsatellites, as well as to estimate the degree to which
microsatellite length and motif are important in determining
Webster, M.T., N.G. Smith, and H. Ellegren, Microsatellite
evolution inferred from human-chimpanzee genomic sequence alignments.
Proc Natl Acad Sci U S A, 2002. 99(13): p. 8748-53.
Speaker: Dimitria Chalkia - Department of Biology -