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IMEG SEMINARS
Spring 2006
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| Previous IMEG
Seminars and Abstracts: |
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Date |
Speaker |
| 01/18/06 |
Speaker:
Dr. David Geiser
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.
References:
O'Donnell
K, Sutton DA, Rinaldi MG, et al.
Genetic
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 |
| 01/25/06 |
Speaker:
Dr. Christipher House - Department of Geosciences
Title: "Linking
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.
The 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 ammonium.
The 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.
References:
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. |
| 02/01/06 |
Speaker:
Dr. Kenneth Weiss -Department of Anthropology and Genetics
Title: "Searching
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.
References:
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02/08/06 |
Speaker:
Dr. 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.
References:
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.
|
| 02/15/06 |
Speaker:
Dr. Webb Miller -Department of Computer Science
Title: "Three
on-going projects."
Abstract: The
talk will sketch three "works in progress":
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
downloaded
from UCSC's Genome Browser for rare genomic changes that suggest or
confirm a
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.
References:
Blanchette 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. (2006)
Metagenomics to paleogenomics: large-scale sequencing of mammoth DNA.
Science 311, 392-394.
|
| 02/22/06 |
Speaker:
Dr. Kai Meuller -Department of Biology
Title: "Phylogenetic
reconstructions in carnivorous and weedy plants and insights on
encoding microstructural changes and bootstrapping given large taxon
samplings."
Abstract:
The talk will cover ongoing
projects on
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reconstructing the phylogeny of the carnivorous plant-family
Lentibulariaceae and related plants, and analyses of extreme
substitutional rate shifts
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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
References:
Müller 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.
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| 03/01/06 |
Speaker:
Dr. Kateryna Makova -Department of Biology
Title: "Mammalian male mutation bias: impacts
of genereation time and regional variation in substitution rates."
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, perissodactyls, and
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.
|
| 03/08/06 |
Speaker: SPRING
BREAK - NO SEMINAR |
|
03/15/06 |
Speaker:
Matt
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. |
| 03/22/06 |
Speaker:
Dr. Claude dePamphilis
-Department
of Biology
Title:
"Genome evolution in
parasitic plants: new genomes, surprising findings."
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.
References:
Bunggard, 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.
|
| 03/29/06 |
Speaker:
Dr. Anton Nekrutenko
-Department of Biochemistry and Molecular Biology
Title: "DUAL
CODING GENES IN HUMAN GENOME."
Abstract:
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.
References:
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 publisher]
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|
04/05/06 |
Speaker:
Xin Ye -Department of
Biology
Title: "Evolutionary Analysis
of Mob Gene Superfamily."
Abstract:
Intercollege 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.
References:
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, 1163–1170.
|
| 04/12/06 |
Speaker: Marc Bouchet -Department of Biology
- Cancelled
Title:
Abstract:
References: |
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| 04/19/06 |
Speaker: Jill Daurte -Department of Biology
Title: "Evolutionary
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.
References:
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.
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| 04/26/06 |
Speaker:
Chungoo Park -Department
of Biology
Title: "UNIQUE
GENOMIC LANDSCAPE UNDERLIES HUMAN X INACTIVATION PROFILE."
Abstract:
Mechanisms 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.
Here 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 elements
contributes to the
expression patterns found on the X chromosome.
References:
(1) 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.
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