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IMEG
SEMINARS
FALL 2002
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Previous
IMEG Seminars and Abstracts: |
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Date |
Speaker and title of seminar |
09/04/02 |
Speaker:
Dr. David Geiser,
Assistant Professor
- Department
of
Plant Pathology
Title:
Applied molecular evolutionary genetics: multilocus phylogenetics of Fusarium, a
plant pathogenic fungus |
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09/11/02 |
Speaker:
Dr. Kazu
Misawa
- Department
of
Biology
Title:
Reanalysis of Murphy et al’s data gives various phylogenetic
trees for the same set of mammalian orders and suggests
over-credibility of Bayesian trees.
Abstract: Murphy et al. (2001) reported that the mammalian phylogeny was
resolved by Bayesian phylogenetics. However, the DNA sequences they
used had many alignment gaps and undetermined nucleotide sites. We
therefore reanalyzed their data by minimizing unshared nucleotide
sites and retaining as many species as possible (13 species). In
constructing phylogenetic trees, we used the Bayesian, maximum
likelihood (ML), and maximum parsimony (MP), and neighbor joining
(NJ) methods with different substitution models. These trees were
constructed by using both protein and DNA sequences. The results
obtained have shown that Bayesian methods often give different
topologies when different types of data (protein and DNA sequences)
and different ways of data analysis were used. The credibility value
obtained for each clade was generally much higher than the bootstrap
values obtained by other tree-building methods. Two different
Bayesian topologies were sometimes supported by high credibility
values, leading to a difficulty of choosing the most likely tree.
This suggests that the credibility value given by Bayesian methods
are often too high to be reliable and there fore the Murphy tree,
which heavily depends on the credibility values, may not be correct.
The bootstrap values obtained by ML, MP, and NJ methods do not give
strong support for the Murphy tree.
Reference:
Murphy, W. J., E. Eizirik, S. J. O'Brien, O. Madsen, M. Scally,
C. J. Douady, E. Teeling, O. A. Ryder, M. J. Stanhope, W. W. de Jong,
and M. S. Springer. 2001. Resolution of the early placental mammal
radiation using Bayesian phylogenetics. Science 294:2348-2351.
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09/18/02 |
Speaker:
Shan Yang, Dept. of Biochemistry,
Microbiology, and Molecular Biology, Penn State Univ.
Title:
Co-variation in divergence by substitution, deletion,
transposition and recombination during mammalian evolution
Abstract: The human genome project provides an enormous amount of information
about our genetic information. At the same time, mouse and
several other mammalian species are being sequenced. The
comparison between human and mouse sequence provides insight into
some fundamental issues in mammalian evolution. Comparative
genomics also provides new approaches to predicting function in both
coding and noncoding regions. The results of the whole genome
human-mouse alignments are freely available at
http://bio.cse.psu.edu/genome/hummus/ as precomputed percent
identity plots and as tracks on the UCSC Genome Browser (http://genome.ucsc.edu).
Many noncoding sequence under selection could be
gene regulatory elements. Finding such candidate function
noncoding sequences is greatly complicated by the variation in the
level of conservation seen across the genome. We are trying to
explain what factors of genomic sequence of human make some regions
more conserved than others.
We studied six measures of evolutionary change in
the human genome. Three of them were derived from the aligned
human and mouse genome. (1) nucleotide substitutions per
4-fold degenerate site in coding regions, (2) nucleotide
substitutions per site in ancestral repeats and (3) fraction of
nonrepetitive human DNA not aligning with mouse, and three are
derived from human genome data along, include (4) SNP density, (5)
frequency of insertion of transposable elements, and (6) rate of
meiotic recombination rate. All these 6 parameters are
measured in megabase windows along the chromosome. It was
found that all six vary significantly genome wide and they vary
together. This suggested that some regions of genome change
faster by all processes that alter DNA while others change slower.
But this regional variation is not completely explained by GC
content in human, change in GC between human and mouse, CpG island
density and density of ancestral transposon relics that predate the
human mouse divergence.
Conservation scores that incorporate the locally
varying neutral rate have been computed genome wide. They can
be examined at the Genome Browser (Mouse Cons track) as an estimate
of predicted level of selection on every aligned sequence.
References:
Ansari-Lari, M. A., J. C. Oeltjen, S.
Schwartz, Z. Zhang, D. M. Muzny, J. Lu, J. H. Gorrell, A. C.
Chinault, J. W. Belmont, W. Miller and R. A. Gibbs. 1998.
Comparative sequence analysis of a gene-rich 16 cluster at
human chromosome 12p13 and its syntenic region in mouse chromosome
6. Genome Res 8: 29-40.
Aquadro, C. F. 1997. Insights into the evolutionary
process from patterns of DNA sequence variability. Curr Opin
Genet Dev 7: 835-840.
Begun, D. J. and C. F. Aquadro.
1992. Levels of naturally occurring DNA polymorphism correlate with
recombination rates in D. melanogaster. Nature 356:
519-520.
Bernardi, G. 1995. The human
genome: organization and evolutionary history. Annu Rev Genet
29: 445-476.
Chiaromonte, F., S. Yang, L.
Elnitski, V. Yap, W. Miller and R. C. Hardison. 2001. Association
between divergence and interspersed repeats in mammalian noncoding
genomic DNA. Proc. Natl. Acad. Sci., USA in press.
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09/25/02 |
Speaker:
Dr. Zhi-Chun Lai,
Associate Professor, Departments of Biology, and Biochemistry &
Molecular Biology, Penn State Univ.
Title:
Cross-talk between Notch and Receptor Tyrosine Kinase Signaling
Pathways
Abstract: Notch and Receptor Tyrosine Kinase (RTK) signaling pathways play a
fundamental role in metazoan development as they provide
evolutionarily conserved mechanisms important for intercellular
communication. However, little is known about how these two
pathways might cross-talk to each other during development. The
Drosophila eye has been used as an experimental system to
address this issue. During Drosophila eye development, one
of the functions mediated by Notch signaling is to restrict cellular
competence for differentiation. Contrary to this, the RTK pathway
provides inductive signals for recruitment of photoreceptors into
developing ommatidia. How these two pathways oppose each other
during differentiation is not clearly understood. A possible answer
to this question lies in the transcriptional regulation of the
yan gene. Yan, a general inhibitor of neural differentiation,
is required to maintain cells in a precursor state prior to
ommatidial recruitment. In our studies, we have isolated an
eye-specific enhancer of the yan gene. We found that Notch
and a critical component of the Notch pathway, Suppressor of
Hairless [Su(H)], are essential for reporter gene transcription via
this 122-bp enhancer as well as endogenous Yan expression. This
activation is disrupted by members of the RTK pathway. One such
member, the ETS-domain protein Pointed (Pnt), is also able to bind
to the yan enhancer and compete with Su(H) for DNA binding.
Thus, the yan gene provides a point where Notch and RTK
pathways intersect in an opposing manner.
Reference:
Rohrbaugh, M., Ramos, E., Nguyen, D., Price, M., Wen, Y., and Lai,
Z.-C. (2002)
"Notch Activation of yan Expression is Antagonized by RTK/Pointed
Signaling in the Drosophila Eye,” Current Biology,
12: 576-581.
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10/02/02 |
Speaker:
Dr. Jim Leebens-Mack,
Associate Professor, Floral Genome Project, Dept. of
Biology, Penn State Univ.
Title:
Uncovering the
Coevolutionary History of the Yucca-Yucca Moth Pollination Mutualism
Abstract:
Yuccas and yucca
moths are tied in an obligate pollination mutualism, commonly cited
as one of the most obvious examples of coevolution. Comparisons of
molecular phylogenies show, however, that extant yucca hosts and
their pollinating yucca moths do not share parallel patterns of
diversification. Whereas a recent burst of diversification (< 5MY)
is evident in a mtDNA-based phylogeny for the yucca moths,
divergence of distinct clades - corresponding to taxonomic sections
- occurred early in the history of the genus Yucca. In
addition, instances of intersectional gene flow in Yucca are
evident in comparisons of gene phylogenies. These issues and the
direction of my future research on this system will be presented.
Background Reading
(Optional):
Pellmyr, O. and J.H. Leebens-Mack. 2000. Reversal of mutualism as a
mechanism for adaptive radiation in yucca moths. American
Naturalist 156:S62-S76.
Pellmyr, O. and J.H. Leebens-Mack. 1999. Forty million years of
mutualism: evidence for eocene origin of the yucca-yucca moth
association. Proceedings of the National Academy of Sciences
96:9178-9183.
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10/09/02 |
Li Hao, Dept. of
Biology, Penn State Univ.
Title: Divergent and Birth-and-Death Evolution of KIR genes
in Higher Primates
Abstract:
A recently identified gene family of natural killer-cell
immunoglobulin-like receptors (KIRs) plays important functions in
the innate immune system. By specifically interacting with major
histocompatibility complex (MHC) class I molecules, they can
regulate the lytic activity of natural killer (NK) cells, which
are characterized by the ability to lyse tumor or virus-infected
cells. Considering their recent emergence in evolution, the KIRs
have unusually high diversity reflected by multiple loci, multiple
haplotypes, multiple alleles, and multiple splicing variants for
the individual locus. Here using the sequences of human and other
primates KIRs, we studied the potential role of natural selection
on the diversification of KIR molecules and the pattern of
long-term evolution of this gene family. The dN/dS
analysis and the inference of the ancestral KIR sequences strongly
suggest that the positive Darwinian selection driven by the
interaction with MHC class I molecules promoted the diversity of
human KIR genes, particularly in the lineage of KIRs with D1+D2
domain organization and HLA-C-binding specificity. Furthermore,
the evolutionary pattern of this gene family agrees with the
birth-and-death model of evolution in which new genes are created
by repeated gene duplication, and some of them are maintained in
the genome at least 26 million years when the OWM diverged from
NWM.
References:
Boyington, J. C., S. A. Motyka, P. Schuck, A. G. Brooks, and P.
D. Sun. 2000. Crystal structure of an NK cell immunoglobulin-like
receptor in complex with its class I MHC ligand. Nature 405:
537-543.
Trowsdale, J. R. Barten, A. Haude, C. A. Stewart, S. Beck, and M.
J. Wilson. 2001. The genomic context of natural killer receptor
extended gene families. Immunol. Rev. 181: 20-38.
Nei, M., Gu, X., and Sitnikova, T. 1997. Evolution by the
birth-and-death process in multigene families of the vertebrate
immune system. Proc. Natl. Acad. Sci. USA 94:7799-7806.
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10/16/02 |
Speaker:
Dr. Kazu Kawasaki,
Depts. of Anthropology and Biology, Penn State Univ.
Title:
Calcium-binding phosphoproteins: The origin of vertebrates?
Abstract:
We
have identified evidence for a common origin of the genes for dental
enamel matrix proteins (EMPs), milk caseins, and salivary
proteins: adjacent chromosomal locations, common structural
features, and specific expression in ontogenically similar tissues.
These proteins are calcium-binding phosphoproteins, and regulate
calcium-phosphate concentration of extracellular environment. Genes
for dentin/bone extracellular matrix proteins also show similar
structural features and constitute a cluster in the vicinity of the
EMP cluster. We speculate that these are also derived from
the common origin.
Conodonts (Late
Cambrian)
appear to have
developed the earliest mineralized exoskeleton as an oral feeding
apparatus, which is composed of both enamel and dentine. Thus,
fossil record cannot resolve the earliest mineralized tissue in
vertebrates.
The sequence of gene duplications of these genes of
extant agnathan will make clear the early events in mineralized
exoskeletal formation, a characteristic of vertebrates. This
cluster may also be informative about the evolution of the
vertebrate head, and of lactation in mammals.
References:
Sansom, I. J.,
Smith, M. P., Armstrong, H. A., and Smith, M. M. 1992. Presence of
the earliest vertebrate hard tissues in conodonts. Science
256: 1308-1311.
Sansom, I. J., Smith, M. P., and Smith, M. M. 1994.
Dentine in conodonts. Nature 368: 591.
Holland, P. W. 1999. Gene duplication: Past, present
and future. Semin Cell Dev Biol 10: 541-547.
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10/23/02 |
Jaime Blair, Dept. of Biology,
Penn State Univ.
Title:
Estimating Divergence
Times in Multicellular Eukaryotes
Abstract:
Understanding the
interactions between biological and geological processes is only
possible with an accurate timeline for each. The Geologic timescale
of Earth is well established from radioisotope dating and the
presence of specific fossils. A timescale for major biological
divergences is not as well established. Here I will present some
recent work estimating divergence times among animals and between
the major groups of multicellular eukaryotes using molecular clock
methods. I will also present some preliminary data using non-clock
methods, and discuss the apparent advantages/disadvantages of each.
References:
Wang et al. Proc. R. Soc. Lond. B 266:163-171 (1999).
Nei et al. PNAS
98:2497-2505 (2001).
Sanderson, MJ. Mol. Biol. Evol.
19:101-109 (2002).
Thorne et al. Mol. Biol. Evol.
15:1647-1657 (1998).
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10/30/02 |
Speaker:
Dr. Yoshihito Niimura,
Dept. of Biology, Penn State Univ.
Title:
The biased base appearance at the second codons in eukaryote
genomes: A possible signal for controlling translation initiation
Abstract:
The codon after the initiation codon affects translation
initiation in bacteria: It is reported that AAA and AAU, the two
most frequent second codons in Escherichia coli, enhance the
translation efficiency in both in vitro and in vivo
translation systems. In this study, we extensively examined
the features of base biases near the gene termini using the
proteomes of seven eukaryotes. We found that the codon appearance
at the second codon is highly biased: NCN is generally preferred, in
particular, GCG is strongly favored in human and plant genes.
We also detected position-dependent base biases characteristic
of each species, such as GC- or C-rich biases observed until about
the 70-th codon for humans or plants. The presence of such biases
implies that the base sequences around the initiation codon,
especially the second codon, control translation of genes in
eukaryote genomes.
References:
Sato, T., Terabe, M., Watanabe, H., Gojobori, T., Hori-Takemoto,
C. and Miura, Ki. 2001. Codon and base biases after the
initiation codon of the open reading frames in the Escherichia
coli genome and their influence on the translation efficiency.
J Biochem. 129: 851-860.
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11/06/02 |
Speaker:
Dr. Cooduvalli Shashikant,
Associate Professor, Dept. of Molecular and Developmental Biology
Title: Hoxc8 Early Enhancer: A Paradigm for Studying Variation
that Reflects Patterning Diversity
Abstract: The Hoxc8 early enhancer is a 200 bp region that
controls early phase of Hoxc8 expression during mouse embryonic
development. This enhancer defines the domain of Hoxc8 expression in
the neural tube and mesoderm of the posterior regions of the
developing embryo. Mutational analyses reveal that at least nine
distinct cis-acting elements, which in different combination determine
reporter gene expression in transgenic embryos in the neural tube,
somites and lateral plate mesoderm. A comparative analysis suggests a
high degree conservation of the enhancer region among vertebrates.
However, several significant variation in the Hoxc8 early enhancer
sequence and activity have been found in different species. These
variations are consistent with changes in Hoxc8 expression, which in
turn correlate with changes in axial morphology among different
species examined. Taken together, we propose that variation in Hoxc8
cis-regulatory sequences may have played a major role in the
diversification of axial morphology among vertebrates.
References:
I will be presenting some of the unpublished results from my
laboratory. References to previous work are:
Shashikant CS, Kim CB, Borbely MA, Wang WC, Ruddle FH.
Comparative
studies on mammalian Hoxc8 early enhancer sequence reveal a baleen
whale-specific deletion of a cis-acting element. Proc Natl Acad Sci U
S A. 1998 Dec 22;95(26):15446-51.
Belting HG, Shashikant CS, Ruddle FH.
Modification of
expression and cis-regulation of Hoxc8 in the evolution of diverged
axial morphology.
Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2355-60.
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11/13/02 |
Speaker:
Dr. Jianzhi Zhang,
Assistant Professor, Dept. of Ecology
and Evolution, Univ. of Michigan
Title:
Tracing functional changes in
protein evolution
Abstract: Abstract: In this talk, I will discuss three case studies in which
we used statistical methods and molecular techniques in delineating
the molecular evolutionary mechanisms behind functional changes
in protein evolution. The three cases are reported in the following
papers:
References:
Zhang, J. and H. F. Rosenberg (2002)
Complementary advantageous substitutions in the evolution of an
antiviral RNase of higher primates. Proc. Natl. Acad. Sci. USA
99:5486-5491.
Zhang, J., Y.-P. Zhang, and H. F.
Rosenberg (2002) Adaptive evolution of a duplicated pancreatic
ribonuclease gene in a leaf-eating monkey. Nature Genet.
30:411-415.
Zhang, J., D. M. Webb, and O. Podlaha
(2002) Accelerated protein evolution and origins of human-specific
features: FOXP2 as an example. Genetics, in press.
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11/20/02 |
Speaker:
Dr. Nikolas Nikolaidis, Dept. of
Biology, Penn State Univ.
Title:
Hsp70 Gene Sequences as Molecular
and Phylogenetic Markers
Abstract:
Nematodes are an important
animal group comprising both parasitic species that threaten the
health of plants, animals, and humans on a global scale, and
free-living species that pervade sediment and soil ecosystems in
overwhelming numbers. Nematode community structure can be used as a
bioindicator in environmental monitoring. Classification and
systematics of Nematodes has been hampered by the lack of reliable
morphological and clearly homologous characters.
The evolutionarily
conserved genetic system of the HSP70 gene family was studied in
several nematode species and populations, attempting to detect
genetic characters in order to distinguish nematode species.
Polymerase chain reactions (PCR) resulted in amplified DNA
fragments, which exhibited distinct and reproducible band patterns
that characterize different nematode species and populations, and
thus we suggest that the different organization of the hsp70
sequences in nematode species can be used as a molecular marker.
A DNA
fragment, encoding 25% of the substrate-binding domain in all
hsp70 sequences, was further used for phylogenetic analyses
among nematodes and between nematodes and other taxa. The results
indicated that this small and easily reproduced sequence could be
used as a molecular phylogenetic marker.
References:
Blaxter, M. L., De Ley, P., Garey, J.
R., Liu, L. X., Scheldman, P., Vierstaete, A., Vanfleteren, J. R.,
Mackey,
L. Y., Dorris, M., Frisse, L. M., Vida, J. T., & W.K.
Thomas, 1998. A molecular evolutionary framework for
the phylum Nematoda. Nature, 392, 71-75.
Ekschmitt, K., Bakonyi, G., Bongers, M.,
Bongers, T., Boström, S., Dogan, H., Harrison, A., Kallimanis,
A.,
Nagy, P., O'Donell, A. G., Sohlenius, B., Stamou, G. P., & V.
Wolters, 1999. Effects of the
nematofauna on microbial energy and
matter transformation rates in European grassland soils. Plant
and Soil, 212, 45-61.
Heschl, M. F. P., & D. L. Baillie,
1990a. The HSP70 multigene family of Caenorhabditis elegans.
Comp.
Biochem. Physiol. B, 96, 633-637.
Hughes, A. L., 1993. Nonlinear
relationships among evolutionary rates identify regions of
functional divergence in heat-shock protein 70 genes. Mol. Biol.
Evol., 10, 243-255.
Marais, G., Mouchiroud, D. & L. Duret,
2001. Does recombination improve selection on codon usage? Lessons
form nematode and fly complete genomes. Proc. Natl. Acad. Sci.
USA, 98, 5688-92.
Morimoto, R. I. 1998. Regulation of the
heat shock transcriptional response: cross talk between a family of
heat shock factors, molecular chaperones, and negative regulators.
Genes Dev., 15, 3788-96.
Nikolaidis, N., & Z. G. Scouras, 2002. A
polymerase chain reaction (PCR) application for free-living
nematodes (Rhabditida) discrimination. Mol. Ecol. Notes, 2,
248-249.
Zhu, X., Zhao, X., Burkholder, W. F.,
Gragerov, A., Ogata, C. M., Gottesman, M. E., & W. A. Hendrickson,
1996. Structural analysis of substrate binding by the molecular
chaperone DNAk. Science, 272, 1606- 1614.
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11/27/02 |
Thanksgiving Holiday |
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12/04/02 |
Speaker:
Kerstin Kauffman,
University of Jena, Germany |
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12/11/02 |
Speaker:
Valer Gotea, Dept.
of Biology, Penn State Univ.
Title:
An Overview of Duplications
Patterns in Several Vertebrate Genomes
Abstract:
Due to the pioneering, independent work of Nei (1969) and Ohno
(1970) we know that duplication is a major force of genomic
evolution. Several studies identified single duplicated genes, or
clusters of duplicated genes before whole genome sequences were
available. We analyzed the publicly available genome sequences of a
few vertebrate organisms, e.g., human, mouse, rat, and Japanese
puffer-fish to identify patterns of duplications in these organisms.
Our preliminary results indicate that several waves of duplications
occurred during this species evolution, but the pattern of
duplications is different for each species. Details of our analysis,
as well as the results of a more in depth analysis of species
duplication patterns will be presented.
References:
Nei, M. 1969. Gene Duplication and
Nucleotide Substitution in Evolution. Nature 221: 40-42
Ohno, S. 1970. Evolution by Gene
Duplication. Springer-Verlag, Berlin
Wong, Z., Royle, N., and Jeffreys
A. 1990. A novel human DNA
polymorphism resulting from transfer of DNA from chromosome 6 to
chromosome 16. Genomics 7: 222-234
Eichler, E. E. 1998. Masquerading
repeats: Paralogous pitfalls of the Human Genome. Genome Res
8: 758-762
Makalowski, W. 2001. Are we polyploids?
A brief history of one hypothesis. Genome Res. 11: 667-670
Bailey, J. A., et al. 2002. Recent
Segmental Duplications in the human genome. Science 297: 1003-
1007
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