IMEG

Institute of Molecular
Evolutionary Genetics

 
 
 
          
 

IMEG SEMINARS
FALL 2002
 
Previous IMEG Seminars and Abstracts:
Fall 2009

Spring 2009

Fall 2008

Spring 2008

Fall 2007 Spring 2007 Fall 2006

Spring 2006
Fall 2005
Spring 2005

Fall 2004
Spring 2004

Fall 2003

Spring 2003
Fall 2002

Spring 2002

Fall 2001

Spring 2001

Fall 2000

Fall 1999

Spring 1998

Fall 1997

 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

 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

 12/04/02 Speaker: Kerstin Kauffman, University of Jena, Germany
   
 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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