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IMEG
SEMINARS
spring 2002
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Previous
IMEG Seminars and Abstracts: |
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Date |
Speaker and title of seminar |
01/16/02 |
Dr. Mark Shriver,
Dept. of Anthropology, Penn State Univ.
Title & Abstract:
1) Update work on estimating
ancestry and the relationships between ancestry and skin
pigmentation in three population samples
2) Provide a review of the idea of "population genomics"
Reference:
Black et al. 2001 Ann. Rev. Entomol. 46:441-469 and show data on
our initial efforts at a study of human population genomics using
the SNP Consortium data. |
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01/23/02 |
Dr. Yoshiyuki Suzuki, Dept. of
Biology, Penn State Univ.
Title:
Simulation study of the reliability and
robustness of the statistical methods for detecting positive
selection at single amino acid sites
Abstract: Inferring positive selection at single amino acid sites is of
biological and medical importance. The parsimony-based methods
have been developed for this purpose, but the reliabilities of these
methods are not well understood. Since the evolutionary models
assumed in these methods are only rough approximations to reality,
it is desirable that the methods are not very sensitive to violation
of the assumptions made. Here we show by computer simulation
that the parsimony-based method is generally conservative, whereas
the likelihood-based method is sensitive to violation of assumptions
under certain conditions and produces many false-positive results.
These observations, together with those from previous real data
analysis, suggest that the parsimony-based method is generally more
reliable than the likelihood-based method.
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01/30/02 |
Dr. Stephen Schaeffer,
Dept. of Biology, Penn State Univ.
Title:
Molecular population genetics of sequence length diversity in
the Adh region of Drosophila pseudoobscura
Abstract: Two hypotheses have been suggested for how natural selection acts on
intron length in natural populations of Drosophila. Carvalho
and Clark (Nature 401:344) have suggested that introns that are
either too large or small are selected against more efficiently in
regions of high recombination, while Comeron and Kreitman (Genetics
156:1175-1190) have suggested that natural selection favors long
introns in regions of low recombination to enhance genetic exchange.
A 3.5 kilobase segment of the Adh region that includes the
Adh and Adh-related genes was sequenced in 139 D.
pseudoobscura strains collected from 13 populations. Insertion
and deletion variation in the Adh region was used to
determine if sequence variation departs from an equilibrium neutral
model for a gene in a high recombination region. A total of 38
deletion and 46 insertion polymorphisms are segregating within D.
pseudoobscura populations. The Tajima test fails to reject a
neutral model for insertion polymorphisms, but an excess of rare
frequency deletions leads to a rejection of a neutral model of
deletions. Insertions and deletions were classified as repetitive
sequences if the added or missing bases were similar to flanking
sequences. The insertions events had a higher frequency of
repetitive polymorphisms than the deletion events (68% repetitive
insertions versus 41% repetitive deletions). Deletions are
nonuniformly distributed among the noncoding regions, while
insertions do not depart from a uniform distribution. These results
suggest that introns in regions of high recombination will tend to
increase in size because purifying selection acts against deletions,
but not insertions. The nonuniform distribution on deletions is
likely to result from selective constraints for intron sequences
necessary for proper splicing. The source of new information for
insertions tends to be sequences that flank the insertion site.
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02/06/02 |
Dr. Malia Fullerton,
Depts. of Anthropology and Biology, Penn State Univ.
Title:
Population Genetic Variation at the
Type 2 Diabetes Candidate Locus Calpain-10
Abstract:
Previous research has suggested that
haplotypes at the calpain-10 locus (CAPN10) are associated with
increased risk of type 2 or non-insulin dependent diabetes mellitus
(NIDDM) in Mexican-Americans, Finns, and Germans (Horikawa et al.
2000). To inform the original mapping results and look for evidence
of the action of natural selection on CAPN10, we undertook a
population-based genotyping survey of the candidate susceptibility
variants. First, we genotyped sites 43, 19, and 63 (the haplotype-defining
variants proposed by Horikawa et al.) and 4 closely-linked SNPs, in
561 individuals drawn from 11 populations from five continents, and
examined the linkage disequilibrium (LD) among them. We then
examined the ancestral state of these sites by sequencing
orthologous portions of CAPN10 in chimpanzee and orangutan. Our
survey identified larger-than-expected differences in the
distribution of CAPN10 susceptibility variants between African and
non-African populations, with common, derived haplotypes in European
and Asian samples (including one of two proposed risk haplotypes)
being rare or absent within Africa. These results suggest a history
of positive natural selection at the locus resulting in significant
geographic differences in polymorphism frequencies, with possible
implications for disease risk.
References:
Fullerton et al. (in press) "Geographic
and haplotype structure of candidate type 2 diabetes susceptibility
variants at the calpain-10 locus" American Journal of Human
Genetics.
Horikawa et al. (2000) "Genetic
variation in the gene encoding calpain-10 is associated with type 2
diabetes mellitus." Nature Genetics, 26:163-75.
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02/13/02 |
Dr. Claude dePamphilis, Dept. of
Biology, Penn State Univ.
Title:
THE FLORAL GENOME PROJECT: An evolutionary genomic approach to
understanding the origin and diversification of floral architecture
Abstract:
The
sudden appearance of flowers in the fossil record about 100 million
years ago represents a longstanding mystery that has long puzzled
evolutionary biologists. Among the many key questions surrounding
the origin of flowers include: Did the ancestral flower possess the
full complement of genetic information needed to assemble a modern
flower? How did the flower (an inherently bisexual structure)
evolve from ancestors that had inherently unisexual reproductive
parts? What components of genetic diversity causes the important
variation in flower diversity that we see today? Recent studies in
plant developmental genetics and genomics have identified dozens of
genes with specific roles in flower development in Arabidopsis
and other model organisms. Despite this rapid progress, many (if
not most) genes with critical roles remain undiscovered, largely
because of functional redundancy. Furthermore, it is still very
unclear the extent to which one or even a few intensely studied
models will lead to general understanding of the floral
developmental process. In this talk, I will describe Floral Genome
Project (FGP), a newly funded study involving multiple collaborators
at Penn State and other universities, that will address these and
other questions about flower origins and diversification.
Because this project has only begun within the last few months, I
will focus on the project goals, basic design features of our
genomic experiments, and how genomic scale data can be used to
address evolutionary hypotheses.
References:
Albert,
V.A., Gustafsson, H.G., and DiLaurenzio, L. 1998. Ontogenetic
systematics, molecular developmental genetics, and the angiosperm
petal. In Soltis, D. E., Soltis, P.S., Doyle, J. J. (eds).
Molecular Systematics of Plants II, pp 349-374. Kluwer, Norwell,
MA.
Barkman, T. J., G.
Chenery, J. R. McNeal, J. Lyons-Weiler, W. J. Elisens, G. Moore, A.
D. Wolfe, and C. W. dePamphilis. 2000. Independent and combined
analyses of sequences from all three genomic comparments converge on
the root of flowering plant phylogeny.
Proceedings of the
National Academy of Sciences 97:13166-13171.
Ma, H. and C. W.
dePamphilis. 2000. The ABCs of flower
evolution. Cell 101:5-8.
The Floral Genome
Project Research Group. 2002. Missing Links: The genetic
architecture of the flower and flower diversification. Trends In
Plant Science 7:22-31.
Baum, D. A., J.
Doebley, V. F. Irish, E. M. Kramer. 2002. Resonse: Missing links:
the genetic architecture of flower and floral diversification.
Trends in Plant Science 7: 31-33.
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02/20/02 |
Open |
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02/27/02 |
Xi Wang, Depts. of
Biochemistry and Mol. Biol., Penn State Univ.
Title:
Molecular and evolutionary aspect of self incompatibility in
flowering plants
Abstract:
In
flowering plants, self-incompatibility (SI) is a widespread
mechanism that prevents self fertilization and promotes outcrossing.
In the simplest case, SI response is genetically controlled by one
multi-allelic loci, and relies on a series of complex cellular
interactions between self-incompatible pollen and pistil. This
multi-alleic SI locus is one of the most highly polymorphic loci
known and has long interested geneticist and evolutionist. The talk
will describe the recent progress made in molecular study with
several plant species and discuss the implications in evolutionary
aspect.
References:
McCubbin AG, Kao T. (2000) Molecular recognition and response in
pollen and pistil interactions. Annu Rev Cell Dev Biol. 16:333-64.
Hughes A.L. (1999) Adaptive evolution of genes and
genomes. New York : Oxford University Press, p110-115.
Matton, D.P., Luu, D.T., Qin, X., Laublin, G.,
O'Broem, M., Maes, O., Morse, D., and Cappadocia, M. (1999).
Production of an S RNase with dual specificity
suggests a novel hypothesis for the generation of new S alleles.
Plant Cell 11, 2087-2097.
Wang X., Hughes A.L., Tshkamoto T.,
Ando, T., and Kao T.H, (2001) Evidence that Intragenic Recombination
Contributes to Allelic Diversity of the S-RNase Gene. Plant
Physiology 125: 1012-1022.
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03/06/02 |
Spring Break |
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03/13/02 |
Dr. Hiroshi Akashi,
Dept. of Biology, Penn State Univ.
Title:
Gene expression and amino acid composition in the Saccharomyces
cerevisiae proteome
Abstract:
Although translational selection at silent sites is well
established, the role of metabolic constraints on protein structure
remains unclear. The yeast proteome was investigated to determine
whether highly expressed genes preferentially encode translationally
superior amino acids. Both oligo DNA array data and major codon
usage were employed to estimate the translation rates of gene. The
usage of a number of amino acids appears to be strongly dependent on
gene expression levels. Relationships between expression and amino
acid usage remain strong both within protein functional categories
and when simple amino acid sequences are removed. Amino acids that
are used preferentially in highly expressed genes tend to be
recognized by relatively abundant tRNA isoacceptors and/or
relatively inexpensive to synthesize. The base composition of
introns does not show a relationship with transcription rates,
suggesting that transcription-dependent mutational processes do not
account for these patterns. In S. cerevisiae, both
synonymous codon usage and the amino acid composition of proteins
appear to reflect natural selection to enhance the translational or
metabolic efficiency of cells.
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03/20/02 |
Brian Lazzaro, Dept. of Biology,
Penn State Univ.
Title:
Is
Selection Acting on Antibacterial Peptide Genes in Drosophila?
Abstract:
Drosophila
kill bacterial pathogens with an array of potent antibacterial
peptides. Because these peptides bind directly to pathogens, they
may be targets of host-pathogen co-evolution. I have sequenced the
coding region and 1-2 kb upstream sequence of 6 antibacterial
peptide genes from 12 naturally occuring D. melanogaster
chromosomes. The genes are very short, limiting power for many
evolutionary analsyses. Nevertheless, there are several indications
that natural selection may be acting on the loci. The inferred
selective history is not compatible with two simple models of
host-pathogen co-evolutionary genetics, evolutionary arms race and
overdomininant/diverisfying selection.
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03/27/02 |
Joel McNeal,
Dept. of Biology, Penn State Univ.Use it or Lose
it: Chloroplast Genome Evolution of the Parasitic Plant Genus
Cuscuta
Title:
Use it or
Lose it: Chloroplast Genome Evolution of the Parasitic Plant Genus
Cuscuta
Abstract:
Since the
appearance of the first autotrophic life on earth, the transition to
heterotrophy has occurred independently many times with profound
repercussions. The multiple origins of parasitism in angiosperms
serve as an excellent system to study molecular evolution of
photosynthetic genes that may be under relaxed functional
constraint. The parasitic plant genus Cuscuta contains well
over 100 species that show considerable variation in pigmentation
and chloroplast structure. Study of chloroplast gene structure and
apparent levels of selection across the taxonomic range of
Cuscuta should provide insight into which genes are most likely
to be lost, which Cuscuta species may still perform residual
photosynthesis, and which chloroplast genes may be under selection
for functions other than photosynthesis.
Comparison with other independently evolved parasitic lineages
will eventually lead to a better understanding of the similarities
in molecular evolution of genes that are under relaxed selection.
References:
dePamphilis, C. W. 1995. “Genes and genomes.” pp. 177-205 in
Parasitic Plants. M. C Press and J. D Graves eds. Chapman and
Hall, London.
Hibberd, J. M., R.
A. Bungard, M. C. Press, W. D. Jeschke, J. D. Scholes, and W. P.
Quick. 1998. “Localization of photosynthetic metabolism in the
parasitic angiosperm Cuscuta reflexa.” Planta 205:
506-513.
Machado, M. A. and
K. Zetsche. 1990. “A structural, functional, and molecular analysis
of plastids of the holoparasites Cuscuta reflexa and
Cuscuta europaea.” Planta 181: 91-96.
Nickrent, D. L., A.
E. Colwell, A. D. Wolfe, N. D. Young, K. E. Steiner, and C. W.
dePamphilis. 1998. “Molecular phylogeny and evolutionary studies of
parasitic plants.” pp. 211-241 in Molecular Systematics of Plants
II: DNA Sequencing. D. Soltis, P. Soltis, and J. Doyle eds.
Kluwer Academic Publishers, Boston.
van der Kooij, T.A.,
K. Krause, I. Dorr, and K. Krupinska. 2000. Molecular, functional,
and ultrastructural characterization of plastids from six species of
the parasitic flowering plan genus Cuscuta.” Planta
210: 701-707.
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04/03/02 |
Open |
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04/10/02 |
Dr. Mark Batzer, Louisiana State
Univ.Alu elements and human genomic variation
Title:
Alu
Elements and Human Genomic Variation
Abstract:
Alu elements have amplified within primate genomes over 65 million
years through a RNA-dependent mechanism, termed retroposition. The
amplification of Alu repeats within the human genome has resulted in
the generation of the largest family of mobile elements within the
human genome with greater
than 1,100,000
copies. Even though there are 1.1
million Alu copies in the human genome, only a limited
number of Alu elements have been capable of mobilization and have
given rise to a series of distinct subfamilies of Alu
repeats that are different genetic ages. Several
thousand Alu elements have integrated
and been fixed within the human genome after the
divergence of humans and African apes. The insertion of Alu elements
within the human genome has resulted in a number of new detrimental
mutations. Most of the newly integrated Alu insertions serve
as an innocuous source of genetic variation with a subset of
identical-by-descent Alu insertion polymorphisms that are useful for
the study of human population relationships. Post integration
recombination events between Alu elements have acted as a means to
create human genetic diversity and generated a variety of human
genetic disorders. The sequence structure of Alu elements that
have integrated within the human genome has also undergone extensive
gene conversion events that impact the accumulation of single
nucleotide polymorphisms within the human genome. Alu elements are
also one of the primary
sources
of microsatellite sequences in the human genome. Thus, Alu
repeats contribute to human genomic diversity in a number of
different ways.
References:
Deininger, P. L. and M. A. Batzer (1993) Evolution of
Retroposons. In "Evolutionary Biology, Volume 27", M. Hect, R.
J. MacIntyre and M. Clegg (Eds), Plenum Publishing Corporation, New
York, pp. 157-196.
Deininger, P. L.
and M. A. Batzer (1999) Alu repeats and human disease.
Molecular Genetics and Metabolism 67: 183-193.
Stoneking, M., J.
J. Fontius, S. Clifford, H. Soodyall, S. S. Arcot, N. Saha, T.
Jenkins, M. A. Tahir, P. L. Deininger and M. A. Batzer (1997)
Alu insertion polymorphisms and human evolution: evidence for a
larger population size in Africa. Genome Research 7:
1061-1071.
Roy, A. M.
, M. L. Carroll , S. V. Nguyen, M. Oldridge, A.-H. Salem, A.
O. Wilkie, M. A. Batzer and P. L. Deininger (2000) Potential
gene conversion and source genes for recently integrated Alu
elements. Genome Research 10: 1485-1495.
Roy-Engel, A. M.
, M. L. Carroll, E. Vogel, R. K. Garber, S. V. Nguyen, A.-H.
Salem, M. A. Batzer and P. L. Deininger
(2001) Alu insertion polymorphisms for the study of human
genomic diversity. Genetics 159: 279-290.
Carroll, M. L., A.
M. Roy-Engel, S. V. Nguyen, A.-H. Salem, E. Vogel, B. Vincent, J.
Myers, Z. Ahmad, L. Nguyen, M. Sammarco, W. S. Watkins, J. Henke, W.
Makalowski, L. B. Jorde, P. L. Deininger, and M. A. Batzer (2001)
Large-scale analysis of the Alu Ya5 and Yb8 subfamilies and their
contribution to human genomic diversity. Journal of Molecular
Biology 311: 17-40.
Roy-Engel, A. M.
, M. L. Carroll, M. El-Sawy, A.-H. Salem, R. K. Garber, S. V.
Nguyen, P. L. Deininger, and M. A. Batzer (In Press)
Non-traditional Alu evolution and primate genomic diversity.
Journal of Molecular Biology
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04/17/02 |
Wen-Ya Ko, Dept. of
Biology, Penn State Univ.
Title:
Molecular Phylogeny of The Drosophila melanogaster
Species Subgroup
Abstract:
Both molecular and
phenotypic evolution have been extensively studied in the
melanogaster species subgroup. However, phylogenetic
relationships within the subgroup remain unresolved. In particular
the D. yakuba - D. teissieri species pair and D.
erecta - D. orena species pair in relation to the D.
melanogaster, D. simulans, D. mauritiana, and D. sechellia
species complex remains unclear. Recent molecular studies do
not converge on a single topology. The purpose of our study was to
reconstruct the molecular phylogeny of the melanogaster
species subgroup using multiple nuclear genes. We have developed a
strategy employing “vectoerette PCR” to efficiently sequence
orthologous genes from even distantly related species. Regions of
the Adh, Adhr, Gld, and ry genes (totally ~7221 bp)
from 6 melanogaster subgroup species (D. melanogaster,
D. simulans, D. teissieri, D. yakuba, D. erecta , and
D. orena ) and 3 of their sister species (D. eugracilis,
D. mimetic, and D. lutescens) were sequenced for
phylogenetic reconstruction. Phylogenetic analyses employed maximum
parsimony, neighbor-joining, and maximum likelihood methods. Our
results reject the currently favored tree topology and strongly
support (with high bootstrap scores) the topology that groups
yakuba -teissieri closest to erecta -orena
pair. Although stationarity of base composition was rejected in our
data, violation of this assumption had no impact on the analysis;
the same tree topology is supported by simple (Jukes-Cantor) and
more complex (non-stationary base composition) models.
References:
Lachaise, D., M. L. Cariou, J. R. David, F. Lemeunier, L. Tsacas et al., 1988
Historical Biogeography of the Drosophila-Melanogaster
Species Subgroup. Evolutionary Biology 22: 159-225.
Powell, J.
R., 1997 Progress and prospects in evolutionary biology : the
Drosophila model. Oxford University Press, New York.
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04/24/02 |
Kristi Montooth, Dept.
of Biology, Penn State Univ.
Title:
Relating
genetic and biochemical variation in metabolic pathways to
physiological performance in Drosophila.
Abstract:
Great strides have been made in understanding the
relationship between flux through metabolic pathways and metabolic
performance in both bacteria and yeast (e.g. Hartl 1989; Edwards and
Palsson 2000; Cornish-Bowden and Cardenas 2001; Zaslavskaia et al.
2001). However, in multicellular organisms, it remains unclear how
variation in the components of energy metabolism relates to
variation in complex whole organism physiological performance. The
network of genes underlying energy metabolism is well characterized
in Drosophila, and this knowledge enables a pathway approach
to dissecting the genetic architecture of physiological
performance. I will present results from two studies quantifying
and modeling genetic and biochemical variation within metabolic
pathways. First, a quantitative genetic analysis, involving
quantitative trait loci (QTL) mapping, of the complex pathway
underlying glycolytic metabolism reveals the importance of trans-regulatory
variation within the metabolic pathways. It also sheds light on the
relationship between metabolism and flight.
Second, I am quantifying biochemical variation at all
three steps in the ethanol and acetic acid metabolic pathway.
Ethanol and acetic acid are relevant environmental stresses for
species of Drosophila that inhabit rotting fruit, and natural
selection for increased tolerance to both ethanol and acetic acid
could allow species of Drosophila to exploit new habitat
niches, as appears to be the case for D. melanogaster
(McKenzie and Parsons 1972; McKenzie and McKechnie 1979). Thus, the
simple linear pathway underlying ethanol and acetic acid
detoxification in Drosophila offers a unique system to study
the genetic response of a pathway to selection. Kinetic models of
variation in alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH)
and acetyl-CoA synthetase (AcCoAS) enzyme activity may better
predict ethanol and acetic acid tolerance in Drosophila than
simple unitary relationships between any single enzyme and
tolerance.
References:
Cornish-Bowden, A., and M. L. Cardenas. 2001.
Silent genes given voice. Nature 409:571-572.
Edwards, J. S., and B. O. Palsson. 2000. The
Escherichia coli MG1655 in silico metabolic genotype: its
definition, characteristics, and capabilities. Proc Natl Acad Sci U
S A 97:5528-33.
Hartl, D. L. 1989. The physiology of weak
selection. Genome 31:183-9.
McKenzie, J. A., and S. W. McKechnie. 1979. A
comparative study of resource utilization in natural populations of
Drosophila melanogaster and D. simulans. Oecologia
40:299-309.
Zaslavskaia, L. A., J. C. Lippmeier, C. Shih, D.
Ehrhardt, A. R. Grossman, and K. E. Apt. 2001. Trophic
conversion of an obligate photoautotrophic organism through metabolic
engineering. Science 292:2073-5.
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