Seminars and Abstracts:
Title: "Fusarium infections of
humans: who are the culprits?"
Abstract: . As cytotoxic therapies are increasingly used
to treat a variety of disease syndromes, opportunistic fungal
infections are becoming more common. Fusarium, a genus of
fungi that is most often associated with plant diseases, often causes
superficial or subcutaneous infections that become disseminated in heavily
immunocompromised individuals, frequently causing death. Certain
morphological species of Fusarium tend to be more commonly associated
with human infections than others, particularly F. solani and F.
oxysporum. However, Fusarium species defined
morphologically have proven generally to be diverse species complexes,
raising the question of whether specific species lineages within them are
associated with human infections. Multilocus phylogenetic analyses of
over 400 members of two of the major complexes, the F. oxysporum
complex and F. solani complex, indicated that diverse isolates
within each complex are associated with human infections, with certain
specific clones and lineages showing the greatest association. Some
of these lineages are associated with specific diseases of plants and other
animals. We conclude that the major agents of infection are those
fusaria that are most common in the environment, including the indoor
environment of hospitals. Certain groups of Fusarium also
exhibit a predilection toward both human and plant disease, a unique
characteristic among the fungi. Human Fusarium infections are
thus likely to be truly opportunistic, caused by a diverse set of competent
pathogens that are commonly encountered by humans.
O'Donnell K, Sutton DA,
Rinaldi MG, et al.
diversity of human pathogenic members of the Fusarium oxysporum complex
inferred from multilocus DNA sequence data and amplified fragment length
polymorphism analyses: Evidence for the recent dispersion of a
geographically widespread clonal lineage and nosocomial origin
JOURNAL OF CLINICAL MICROBIOLOGY 42 (11): 5109-5120 NOV 2004
Christipher House - Department of Geosciences
Taxonomy with Environmental Geochemsitry: the Anaerobic Oxidation of
Methane in Cold Seeps & deeply Buried Marine Sediments."
Abstract: The linking of molecular taxonomy
(including 16s rRNA) to environmental geochemistry is a powerful way to
work out the interactions, metabolic activities, and food webs of
microorganisms in their natural setting, whether it is sediment, soil, or a
water column. To this end, we developed a method for coupling an
extant microorganism’s genetic information with geochemical data derived
from the direct analysis of its cell. FISH–SIMS combines fluorescent
in-situ hybridization (FISH) with secondary ion mass spectrometry
(SIMS). FISH is a culture-independent technique used to visually
identify naturally occurring microorganisms by staining their ribosomal
RNA. Secondary ion mass spectrometry (SIMS) is a method by which
geochemical information can be obtained from microsamples. Using FISH-SIMS,
a researcher can measure a target cell’s isotopic or elemental composition
in a mixed environment.
identification and study of methane-consuming microorganisms is an
important step toward understanding the methane cycle and microbial response
to methane release. The recent identification of two distinct Archaea
capable of anaerobic methane oxidation was in part accomplished using
FISH-SIMS. Because natural methane is highly depleted in 13C,
FISH-SIMS is particularly powerful at determining if a particular cell,
collected from the environment, consumed methane as a substrate for its
cell carbon. This research demonstrated that both the ANME-1 and ANME–2
Archaea from the Eel River Methane Seep are highly depleted in 13C due to
growth on methane. Most recently, we have aimed to track the activity
of cells in the cell cluster by monitoring both their natural carbon
isotopic composition and their incorporation of isotopically-labeled
deep marine biosphere is thought to contain abundant microbial inhabitants,
estimated to be a tenth of the Earth’s total biomass. Sediments from this
environment were recovered during Ocean Drilling Program (ODP) Leg 201, and
were analyzed by both molecular biological and organic geochemical
techniques. Of particular interest in these sediments were four
sulfate/methane transition zones seen at ODP Sites 1227, 1229 and 1230, two
of which coincided with strongly elevated cell counts. Archaeal cells in these
zones were analyzed for abundance and d13C composition by whole cell
analysis (FISH-SIMS) and intact membrane lipids (HPLC-ESI-MSn). Cell counts
showed greater archaeal abundance than bacterial, which was reflected by
intact membrane lipid abundance. Isotopic compositions by both techniques
(often around -20‰) suggest that methane is not an important carbon source
for these cells. Autotrophic carbon fixation appears to be an unlikely
metabolism given the relationship between the isotopic composition of DIC
and archaeal biomass. The isotopic evidence suggests that the bulk archaeal
community is heterotrophic, possibly mediating the oxidation of methane
without consuming it as a carbon source.
The importance of
these techniques is that the cells targeted for study can be environmental
species that cannot currently be grown in the laboratory. These
techniques promises to become critical for working out the interactions,
metabolic activities, and food webs of microorganisms in their natural
setting, whether it is sediment, soil, or a water column.
Orphan, V. J., Ussler III, W., Naehr, T.,
House, C.H., Hinrichs, K. U. and Paull, C. K., 2004.
Geological, Geochemical, and Microbiological Heterogeneity of the Seafloor
Around Methane Vents in the Eel River Basin, offshore California.
Chemical Geology, 205: 265-289.
Kenneth Weiss -Department of Anthropology and Genetics
for olfactory receptor regulators."
Abstract: .Olfactory receptors are the largest class of
vertebrate genes and evolve by a history of gene gain, loss, and
translocation. These 1000 genes are dispersed across the mammalian
genome. Yet, only one gene (and only from one homolog) is expressed in each
of the millions of olfactory neurons. I'm reporting on work in
progress that I began last summer in a sabbatical leave in England, to try
to identify regulatory sequence signals that could begin to explain this
phenomenon. There are various kinds of orderliness in the system, and
some precedents from other genes in various organisms. But it is not
yet clear what kinds of signal we should be looking for, or how to look.
Wojciech Makalowski -Department of Biology
Title: "The comparative genomics of
honeybee spliceosomal RNAs."
Abstract: We have examined
the number and distribution of putative snRNA genes in the Apis mellifera
genome and used this as a basis for an analysis of the pattern of
conservation of snRNA genes among insect genomes (Tribolium castaneum,
Bombyx mori, Anopheles gambiae, Aedes aegypti and six Drosophila
species). Small nuclear RNA sequence variants within a species,
including those observed to previously observed to show regulated expression
in Drosophila melanogaster, are not conserved between species.
Instead, the pattern of sequence variation is more suggestive of neutral
variation than functional differentiation. Promoters for different snRNAs
within each insect species share similar sequence motifs that are likely to
correspond to the binding sites of snRNA-specific transcription factors
such as SNAPc. In striking contrast, there is little conservation of
these promoter elements between different insect species. Those
snRNAs that are specific for the minor spliceosome (U11, U12, U4atac and
U6atac) accumulate fixed nucleotide differences at a much higher rate than
do snRNAs found in the major spliceosome. In addition, the genus
Drosophila is characterized by both a loss of U12 introns and rapid
evolution (or loss) of components of the minor spliceosome.
Hastings, M.L. and A.R. Krainer,
Pre-mRNA splicing in the new millennium. Curr Opin Cell Biol, 2001. 13(3):
p. 302-9., Eddy, S.R. and R. Durbin, RNA sequence analysis using covariance
models. Nucleic Acids Res, 1994. 22(11): p. 2079-88., Schneider, C., C.L.
Will, J. Brosius, M.J. Frilander, and R. Luhrmann, Identification of an
evolutionarily divergent U11 small nuclear ribonucleoprotein particle in
Drosophila. PNAS, 2004. 101(26): p. 9584-9589.
Webb Miller -Department of Computer Science
Abstract: The talk will sketch three "works in
1. Computational reconstruction of the boreoeutherian ancestral genome.
Blanchette et al. (2004)
Reconstructing large regions of an ancestral mammalian genome in silico.
Genome Research 14, 2412-2423.
2. A set of programs to search annotation, sequences, and alignments
from UCSC's Genome Browser for rare genomic changes that suggest or confirm
phylogenetic tree topology.
Rokas and Holland (2000)
Rare genomic changes as a tool for phylogenetics.
Trends Ecol. Evol. 15, 454-459.
3. Sequencing the mammoth genome.
Poinar et al. (2006)
Metagenomics to paleogenomics: large-scale sequencing of mammoth DNA.
Science 311, 392-394.
et al. (2004)
Reconstructing large regions of an ancestral mammalian genome in silico.
Genome Research 14, 2412-2423., Rokas and Holland (2000) Rare genomic changes
as a tool for phylogenetics. Trends Ecol. Evol. 15, 454-459., Poinar et al.
Metagenomics to paleogenomics: large-scale sequencing of mammoth DNA.
Science 311, 392-394.
Speaker: Dr. Kai
Meuller -Department of Biology
reconstructions in carnivorous and weedy plants and insights on encoding
microstructural changes and bootstrapping given large taxon
Abstract: The talk will cover ongoing projects on
- reconstructing the phylogeny of the carnivorous
plant-family Lentibulariaceae and related plants, and analyses
of extreme substitutional rate shifts
- reconstructing the phylogeny of Amaranthaceae, the
food of the Aztecs, with insights on the evolution of
highly derived, unique pollen features
- a set of software tools and thoughts about methods
to deal with a) estimating node support when analyzing a great number
of taxa, b) encoding microstructural changes, in particular in cpDNA
evolving at high length-mutational rates
K (2005) Incorporating information from length-mutational events into
phylogenetic analysis. Molecular Phylogenetics and Evolution, doi:10.1016/j.ympev.2005.07.011
Müller K (2005) The efficiency of different search strategies in estimating
parsimony jackknife, bootstrap, and Bremer support. BMC Evolutionary
Biology, 5, 58. Müller K, Borsch T (2005) Phylogenetics of
Amaranthaceae based on matK/trnK sequence data - evidence from parsimony,
likelihood, and Bayesian analyses. Annals of the Missouri Botanical
Garden, 92, 66-102 Müller K, Borsch T (2005) Phylogenetics of Utricularia
(Lentibulariaceae) and molecular evolution of the trnK intron in
a lineage with high substitutional rates. Plant Systematics and
Evolution, 250, 39-67.
Kateryna Makova -Department of Biology
Title: "Mammalian male
mutation bias: impacts of genereation time and regional variation in
Abstract: In mammals, males
undergo a greater number of germline cell divisions
compared with females. Thus, the male
germline accumulates more DNA
replication errors, which result in male
mutation bias the higher
mutation rate for males than for females.
The phenomenon of male
mutation bias has been investigated
mostly for rodents and primates,
however, it has not been studied in
detail for other mammalian
orders. Here we sequenced and analyzed
five introns of three genes
(DBX/DBY, UTX/UTY, and ZFX/ZFY) homologous
between X and Y
chromosomes in several species of
perissodactyls (horses and rhinos)
and of primates. Male mutation bias was
evident: substitution rate
was higher for a Y chromosome intron than
for its X chromosome
homolog for all five intron pairs
studied. Substitution rates varied
regionally among introns sequenced on the
same chromosome and this
variation influenced male mutation bias
inferred from each intron
pair. Interestingly, we observed a
positive correlation in
substitution rates between homologous X
vs. Y introns as well as
between orthologous primate and
perissodactyl introns. The male-to- female mutation rate ratio estimated
from concatenated sequences of
five perissodactyl introns was 3.88 (95%
CI = 2.90-6.07). Using the
data generated here and estimates
available in the literature, we
compared male mutation bias among several
mammalian orders. We
conclude that male mutation bias is
significantly higher for
organisms with long generation times (primates,
felids) than for organisms with short
generation times (e.g.,
rodents) since the former undergo a
greater number of male germline
References: Li, W.-H., S. Yi,
and K. D. Makova. 2002. Current Opinions in
Genetics and Development. Male-driven
evolution 12: 650-656.
BREAK - NO SEMINAR
Heinicke -Department of Biology
Title: "Systematics and
biogeography of the genus Eleutherodactylus."
Abstract: The neotropical
frog genus Eleutherodactylus is the largest among terrestrial vertebrates,
with greater than 700 described species. Eleutherodactylus species
dominate the amphibian faunas of the West Indies and northern Andes, and
are also well-represented in Central America and other parts of South
America. Phylogenetic relationships within the genus have proven
difficult to resolve through traditional morphology-based
systematics. However, molecular data have proven more useful.
We used sequences of 12S and 16S ribosomal RNA genes to infer relationships
within Eleutherodactylus. Our data indicate that the West Indian
species stem from a single, ancient radiation and that many South American
species belong to a second large radiation centered on the Andes.
References: Crawford, A.J. and
E.N. Smith. 2005. Cenozoic biogeography and evolution in direct-developing
frogs of Central America (Leptodactylidae: Eleutherodactylus) as
inferred from a phylogenetic analysis of nuclear and mitochondrial genes.
Molecular Phylogenetics and Evolution 35 (3), 536-555.
Claude dePamphilis -Department of Biology
evolution in parasitic plants: new genomes, surprising
Abstract: Although most species of flowering plants are
free-living and fully photosynthetic about 1% of plant species are direct
parasites on photosynthetic plants, and as a result lead partly to fully
heterotrophic lifestyles. How parasitism originated and how their
genomes evolve under dramatically altered evolutionary constraints are
fundamental problems. The first parasitic plant studied in any detail
was Epifagus virginiana, a nonphotosynthetic plant that retains
greatly reduced, but evidently functional plastid genomes that encode a
small number of genes for nonphotosynthetic function. The insights
gained from studying the Epifagus plastid genome were wide-ranging
and provide a starting point for this lecture. We have recently
completed new plastid genome sequences in a number of parasitic species
that represent independent origins of parasitism within the flowering
plants. These new plastid genomes provide many surprising
findings, including examples of unexpected retention of photosynthetic genes
and pathways in some entirely heterotrophic species and almost perfect
parallel reduction in gene content in others. There is even the
possibility that some nonphotosynthetic plants have entirely lost their
plastid genomes entirely. While plastid and mitochondrial genomes are
now the focus of intensive study in parasitic plants, the nuclear genome of
parasites remains nearly unexplored. I will conclude with a few
unexpected observations about the nuclear genomes of parasites.
Ralph A. 2004. Photosynthetic evolution in parasitic
plants: Insight from the chloroplast genome. BioEssays 26:
235-247., Cui, L, N. Veeraraghavan, A. Richter, K. Wall, R. K. Jansen, J.
Leebens-Mack, I. Makalowska, and C. W. dePamphilis. ChloroplastDB: the
chloroplast genome database. Nucleic Acids Research, 2006, vol. 34,
Database issue, D692-D696., dePamphilis, C.W., and Palmer, J.D. Loss of
photosynthetic and chlororespiratory genes from the plastid genome of a
nonphotosynthetic plant. Nature 1990, 348:337-339., Leebens-Mack,
J.H. and C.W. dePamphilis. Power analysis of tests for loss of selective
constraint in cave crayfish and nonphotosynthetic plant lineages. Molecular
Biology and Evolution 2002, 19:1292-1302., McNeal, J.R., J.H.
Leebens-Mack, C.W. dePamphilis. Utilization of fosmid partial genomic
libraries for sequencing complete organellar genomes. Submitted to
Biotechniques. Under review.,
Mower JP, Stefanovic S, Young GJ, Palmer JD (2004) Gene transfer from
parasitic to host plants. Nature 432: 165-166., Wolfe H, Morden CW,
Palmer JD (1992) Function and evolution of a minimal plastid genome from a
nonphotosynthetic parasitic plant. Proc. Natl. Acad. Sci. USA 89:
10648-10652., Young, N.D. and C.W. dePamphilis. Rate variation in parasitic
plants: correlated and uncorrelated patterns among plastid genes of
different function. BMC Evolutionary Biology 2005, 5:16.
Anton Nekrutenko -Department of Biochemistry and Molecular Biology
Title: "DUAL CODING
GENES IN HUMAN GENOME."
1Center for Comparative Genomics and
Bioinformatics, Penn State
University, University Park, PA, USA
2Dept. of Computer Science, Faculty of
Sciences, Vrije Universiteit,
Amsterdam, The Netherlands
Genes with overlapping reading frames
(dual coding) are frequently
found in viral genomes but though to be
non-existent in eukaryotes.
However, three known cases (XBP1,
p16INK4A and XLaS) have been
studied in mammals so far and show a
remarkable pattern of co- evolution between the two frames. Are there more
of these unexpected
cases in the human genome? A new
comparative approach designed in our
laboratory yielded a number of additional
candidates based on high
stringency criteria including
conservation in other species (mouse,
rat and/or dog), the overlap length, and
the results of the position- specific transition-transversion ratio test.
Most of the candidate
genes are expressed in the nervous
system. Why do human genome
contain such genes? Here we attempt to
answer this question.
1: Nekrutenko A, Wadhawan S,
Goetting-Minesky P, Makova KD.
Oscillating Evolution of a
Mammalian Locus with Overlapping Reading
PLoS Genet. 2005 Aug 12;1(2):e18 [Epub
ahead of print]
PMID: 16110341 [PubMed - as supplied by
Speaker: Xin Ye
-Department of Biology
Analysis of Mob Gene Superfamily."
Program in Genetics, Institute of Molecular Evolutionary Genetics
Department of Biology
A main cause of tumor development is
mutations in tumor-suppressor genes, which normally function as negative
regulators of cell proliferation or positive regulators of apoptosis. We
have newly identified a tumor-suppressor gene named mats (mob as
tumor suppressor) whose loss-of-function mutation was shown to be able
to induce tumors in Drosophila. The protein encoded by mats
is highly conserved both in amino acid sequence and biological function
between human and Drosophila. To investigate more about this
conserved gene family, we carried out a series of evolutionary studies. An
exhaustive database search identified Mob genes present in a variety
of eukaryotes from the primitive Giardia to animals and
plants. Phylogenetic analysis classifies Mob genes into four major
groups (Group I-IV). Interestingly, Mob’s from species like Giardia and
slime mold are present in almost all groups, suggesting that the major
duplications that gave rise to the members of the Mob family should have
occurred very early in evolution. Each major Mob group contains only one
gene from invertebrates but some groups have more than two genes from
vertebrates, suggesting that additional duplication events have resulted in
the different gene repertoire of the vertebrates. The observed branching
pattern suggests that orthologous Mob proteins could accommodate similar
functions. This pattern coincides with the functional study which demonstrated
that a human Mats ortholog of group I (Mats group) could rescue the
tumor phenotype of Drosophila mats mutant. We also looked at the
transcripts levels of human Mob genes which displayed the ubiquitous
expression pattern in most tissues throughout development. Moreover,
protein sequences alignments showed high conservation level among four Mob
groups, which might indicate their important function. In addition, we have
identified and mapped the conserved amino acid changes to the simulated
3-dimensional structure of Mob proteins, to gain an insight into the
putative functional divergence between the paralogous Mob genes.
Lai, Z. C. et al. (2005). Control of cell proliferation and apoptosis
by mob as tumor suppressor, mats. Cell 120, 675-685. Luca, F.C et al. (1998).
MOB1, an essential yeast gene required for completion of mitosis and
maintenance of ploidy. Mol. Biol. Cell 9, 29–46. Bichsel, S J. et
al. (2004). Mechanism of activation of NDR (Nuclear Dbf2-related) protein
kinase by the hMOB1 protein. J. Biol. Chem. 279, 35228–35235.
Stavridi, E S. et al. (2003). Crystal structure of a human Mob1 protein:
toward understanding Mob-regulated cell cycle pathways. Structure 11,
Bouchet -Department of Biology - Cancelled
Daurte -Department of Biology
dynamics of single copy nuclear genes in flowering plants."
authors: Duarte, J. M., Beckmann,
K., Wall, P. K., Leebens-Mack, J., Ma., H., dePamphilis, C.W.
Abstract: Although all major lineages of angiosperms now appear
to have undergone repeated rounds of ancient genome duplication and most
genes belong to multigene familes, there are numerous nuclear genes that
persist as single copies. In order to understand the molecular
evolution of these single copy genes, we have undertaken a bioinformatic
analysis of ~1500 nuclear genes that are single copy in both Arabidopsis
and rice as well as a detailed phylogenetic analysis for twenty of these
genes. Results indicate these genes have distinct sequence
characteristics and functional affiliations, and are likely subject to
selection to maintain low copy number.
Chapman, B.A., J.E.
Bowers, F.A. Feltus, and A.H. Paterson. 2006. Buffering of crucial
functions by paleologous duplicated genes may contribute cyclicality to
angiosperm genome duplication. PNAS 103: 2730-2735.
Cui, L., P.K.
Wall, J. Leebens-Mack, B.G. Lindsay, D.E. Soltis, J.J. Doyle, P.S. Soltis,
J. Carlson, A. Arumuganathan, A. Barakat, V. Albert, H. Ma, and C.W.
dePamphilis. 2006. Widespread genome duplications throughout the history of
flowering plants. Genome Research in press.
Duarte, J.M., L.
Cui, P.K. Wall, Q. Zhang, X. Zhang, J. Leebens-Mack, H. Ma, N. Altman, and
C.W. dePamphilis. 2006. Expression Pattern Shifts Following Duplication
Indicative of Subfunctionalization and Neofunctionalization in Regulatory
Genes of Arabidopsis. Mol. Biol. Evol. 23: 469-478.
Park -Department of Biology
GENOMIC LANDSCAPE UNDERLIES HUMAN X INACTIVATION PROFILE."
to coordinately control gene expression over large genomic distances are complex
and must involve, at some level, the underlying DNA sequence. Mammalian X
chromosome inactivation represents one of the most fascinating examples of
such mechanisms in action. Indeed, most genes on one X chromosome are
silenced, while ~15% of X-linked genes escape inactivation and yet another
~10% exhibit variable patterns of inactivation among individuals (Carrel
and Willard 2005). However, what drives such differences in expression
among X-linked genes is not well understood. One family of repetitive
elements, LINE-1 (L1), has been proposed to play a role in the chromosomal
control of X inactivation. Namely, since the X chromosome is enriched in
L1s as compared with autosomes, these elements were hypothesized to
represent “way stations” for spreading the X inactivation signal (Lyon
1998). In agreement with this hypothesis, an L1 density gradient was found
along a recently sequenced human X: regions with a higher density of L1s,
which are usually located in more ancient evolutionary strata, harbor larger
numbers of X-inactivated genes than other regions (Ross et al. 2005). It is
not clear, however, whether L1s accumulated there due to their importance
in X inactivation or simply because such regions had more time to do so as
compared with the younger strata.
we utilized an experimentally derived comprehensive inactivation profile of the whole human X chromosome (Carrel
and Willard 2005) and developed a rigorous
bioinformatic and statistical framework to identify candidate sequences
that potentially determine inactivation status of human X chromosome genes.
We focused our analysis on the nonpseudoautosomal portion of Xp22
that possesses the youngest evolutionary strata on X. Inactive X expression
patterns in Xp22 are striking; approximately half of the genes tested in Xp22 escape X inactivation, in
contrast with only 10% of genes outside of Xp22. Additionally, Xp22
genes that escape inactivation map to large clusters, providing compelling
support for regional models of gene control. Interestingly, Xp22 is
depleted of L1s compared with the rest of X chromosome.
We subdivided Xp22 into two subgenomes:
Inactivated (I) and Escaping (E) inactivation. Each subgenome
consisted of clusters of neighboring genes with the same (either I or
E) expression status. The two subgenomes were searched for
overrepresented oligomers (8- to 24-mers). Significance of
overrepresentation was assessed by a permutation test. Using oligomers that
were significantly enriched in the I vs. E Xp22
subgenome (or vice versa) as classification features, and data from
the Xp22 region as training sets, we performed Linear Discriminant Analysis
(LDA). Cross-validation within the training data showed success rates of
80-90% in predicting the expression status of Xp22 genes, and we obtained
promising results also when predicting the expression status of X
chromosome genes outside of Xp22. Interestingly, almost all oligomers
significantly overrepresented in the I subgenome of Xp22 are located
within L1 elements, even though L1 frequencies are similar in the I
and E subgenomes of Xp22. This supports the importance of L1
elements in X chromosome inactivation. Our results suggest that the
chromatin microenvironment which is composed of multiple genomic sequence
to the expression patterns found on the X chromosome.
Carrel and Willard. X-inactivation profile reveals extensive variability in
X-linked gene expression in females. 2005. Nature 2005 434 400-404 (2) Chow
et al. Silencing of the Mammalian X Chromosome. 2005 Annu. Rev. Genomics
Hum. Genet. 6:69-92.