IMEG

Institute of Molecular
Evolutionary Genetics

 
 
 
          
 

IMEG SEMINARS
Spring 2004
 
Previous IMEG Seminars and Abstracts:

  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

 01/14/04


Speaker: Dr. Arthur Lesk, Dept. of Biochemistry and Molecular Biology, Penn State University


Title: "Evolution of the globins."


Abstract: Globins have been subjects of studies of molecular evolution because of the availability of sequence and structural data.  Many important principles have been developed in studies of this family.  Although the field was considered "cut-and-dried" recent discoveries, of truncated globins that differ very substantially from those known before, have reopened many questions about the conserved and variable features of these molecules.

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 01/21/04

Speaker: Dr. Steven Schaeffer, Dept. of Biology, Penn State University


Title: "Comparative Genomics of Drosophila: A repetitive element is found at rearrangement breakpoints in D. pseudoobscura."


Abstract: Inversion mutations reshape Drosophila genomes by shuffling the order of genes within chromosomes.  Levels of inversion diversity differ among chromosomal arms within and between species, but the mechanism that generates these rearrangements is not widely understood.  Comparative analysis of the D. melanogaster and D. pseudoobscura genomes rejects a random chromosomal breakage model. An analysis of sequences in the neighborhood of conserved linkage breaks identifies a novel conserved sequence motif that is found at elevated frequency at intra- and interspecific breakpoints in D. pseudoobscura and may serve as a hotspot for genomic rearrangements.  This talk will also provide an overview of future Drosophila genome projects that are currently underway.


Reference:
Schaeffer, S. W., P. Goetting-Minesky, M. Kovacevic, J. Peoples, J. L. Graybill et al., 2003. Evolutionary genomics of inversions in Drosophila pseudoobscura: Evidence for epistasis. Proceedings of the National Academy of Sciences USA 100:8319-8324.

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 01/28/04

Speaker: Dr. Jim Marden, Dept. of Biology, Penn State University


Title: "Alternative splicing, muscle contraction and intraspecific variation of dragonfly flight muscle."


Abstract: Flight muscles of Libellula pulchella dragonflies contain a mixture of six alternatively spliced transcripts of a single troponin T (TnT) gene.  Intraspecific variation in the relative abundance of different TnT transcripts affects the calcium sensitivity of skinned muscle fibers and the performance of intact muscles during work loop contraction regimes that approximate in vivo conditions during flight.  The relative abundance of one TnT transcript, or the pooled relative abundance of two TnT transcripts, shows a positive correlation with a ten-fold range of variation in calcium sensitivity of skinned fibers (r2=0.77, p<0.0001), and a three-fold range in peak specific force (r2=0.74, p<0.0001), specific work per cycle (r2 = 0.54; p < 0.0001), and maximum specific power output (r2=0.53, p= 0.0002) of intact muscle. Muscle power output of individual male dragonflies is positively related to their total fat content and to their mating success.  Thus, it appears that alternative splicing of TnT is regulated in a manner that allows a finely tuned match between muscle energy expenditure and energy supply.  Individual males able to accumulate more energy have more powerful muscle and higher fecundity.  Gregarine gut parasites interact with this system in some interesting ways that we are now beginning to examine at the molecular level.  There is also interesting spatial variation in the incidence of gut parasites that is associated with soil quality and habitat productivity, which may affect prey abundance and the ability of dragonflies to resist infection.


References:
Marden, J. H., G.H. Fitzhugh, M. Girgenrath, M. R. Wolf, and S. Girgenrath, 2001. Alternative splicing, muscle contraction and intraspecific variation: associations between troponin T transcripts, calcium sensitivity, and the force and power output of dragonfly flight muscles during oscillatory contraction. J. Exper. Biol. 204:3457-3470.
Relates TnT transcripts to muscle contractility.

Marden, J.H., G.H. Fitzhugh, M.R. Wolf, K.D. Arnold, and B. Rowan, 1999. Alternative splicing, muscle calcium sensitivity, and the modulation of dragonfly flight performance. PNAS 96:15304-15309.
Relates TnT transcripts to free flight wingbeat kinematics.

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 02/04/04

Speaker: Fabia Battistuzzi, Dept. of Biology, Penn State University


Title: "A genomic timescale of prokaryote evolution."


Abstract: The concept of molecular clocks has been applied to many different groups of organisms but a timeline of the major divisions of the prokaryotes is still lacking. Through the application of a local-clock method to a concatenated set of genes we estimated a timeline of the major groups of prokaryotes followed by an analysis of their metabolisms. The role played by these metabolisms on the geochemical conditions during the archean eon suggests that a molecular evolutionary approach could be important not only to outline the phylogenetic history of the prokaryotes but also as a key to the early history of Earth. The analysis of the divergence times of ecologically important groups has suggested, for example, an early evolution of methanogenesis, as well as insights into the evolutionary history of others metabolisms.


Reference:
A. Knoll, 2003.The geological consequences of evolution. Geobiology 1:3-14.

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 02/11/04

Dr. Izabella Makalowska, Dept. of Biology, Penn State University


Title: "Mammalian overlapping genes."


Abstract:
It is believed that 3.2 billion base pairs of the human genome harbor about 35,000 protein-coding genes. On average one could expect one gene per 300,000 nucleotides. Although, the distribution of the genes in the human genome is not random, it is rather surprising that a large number of genes overlap in the mammalian genomes. Thousands of overlapping genes were recently identified in the human and mouse genomes. However, the origin and evolution of overlapping genes are still unknown. We identified 1,316 pairs of overlapping genes in humans and mice and studied their evolutionary patterns. It appears that these genes do not demonstrate greater than usual conservation. Studies of the gene structure and overlap pattern showed that only a small fraction of analyzed genes preserved exactly the same pattern in both organisms.


References:
Veeramachaneni V, W. Makalowski, M. Galdzicki, R. Sood, and I. Makalowska, 2004. Mammalian overlapping genes - the comparative perspective. Genome Research 14:280-286.

Lehner, B., G. Williams, R. D. Campbell, and C. M. Sanderson, 2002. Antisense transcripts in the human genome. Trends Genet 18:63-65.

Shendure, J. and G. M. Church, 2002. Computational discovery of sense-antisense transcription in the human and mouse genomes. Genome Biol 3: RESEARCH0044.

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 02/18/04

Speaker: Dr. Hong Ma, Dept. of Biology, Penn State University


Title: "Functional dissection of the Arabidopsis RAD51 gene family encoding recombination and DNA repair enzymes."


Abstract: DNA double-stranded breaks (DSBs) can form during DNA replication and are induced by DNA damaging radiation and chemicals, and must be repaired to allow cell cycle progression.  A major pathway for repairing DSBs relies on homologous recombination.  In fact, meiotic homologous recombination requires the generation of DSBs by specific enzymes.  In yeast, members of the RAD51 family encode homologs of the E. coli recA recombination protein, and are required for repair of DNA damage by radiation and for meiotic recombination.  In Drosophila and mammalian and chicken cell culture, RAD51 homologs are critical for DSBs repair caused by radiation or chemicals.  Furthermore, mouse knockout mutants of some RAD51 homologs are embryonic lethal, whereas yeast and Drosophila mutants are viable.  As in yeast, RAD51 homologs are important for meiosis in Drosophila, but their role in vertebrate animals is not known due to the early lethality.  Arabidopsis has putative orthologs for at least four of mammalian RAD51 homologs.  One of these was known to be required for meiosis in Arabidopsis and yeast.  We have analyzed the function of the other three and found that each is required for meiosis, but dispensable for mitotic growth.  We will discuss possible implications of these results on the conservation and divergence of this gene family in the context of DNA repair, meiosis, and cell cycle regulation.


References: There are many papers on this topic.  The following might serve as a reference:
Trends Biochem Sci. 2001 Feb; 26:131-6.
The Rad51 and Dmc1 recombinases: a non-identical twin relationship. Masson JY, West SC.
Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, EN6 3LD, Herts, UK.
A double-strand break in genomic DNA that remains unrepaired can be lethal for a cell. Indeed, the integrity of the genome is paramount for survival. It is therefore surprising that some cells deliberately introduce double-strand breaks at certain times during their life cycle. Why might they do this? What are the benefits? How are these breaks repaired? The answers to these questions lie in understanding the basis of meiotic recombination, the process that leads to genetic variation. This review summarizes the key roles played by the two recombinases, Dmc1 and Rad51, in the faithful repair of DNA breaks.

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 02/25/04

WUN Bioinformations Online Seminar Series

Location:  310 Rider II         Time:  12:00 p.m. (Noon)

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 03/03/04

Speaker: Valer Gotea, Dept. of Biology, Penn State University


Title: "Transposable elements can be found in protein structures."


Abstract: The high content in repetitive elements of eukaryotic genomes has intrigued many. Because little was known about their precise function, they were included in the category of "junk" DNA, and regarded as unnecessary components of our genomes, or even as genomic parasites and selfish DNA. Lately, however, they are more and more regarded as genomic treasures, as evidence of their coding capacity and regulatory function started to emerge. Different studies have shown that transposable elements fragments can be found in many protein coding genes, but none has shown three dimensional models of proteins containing such fragments, which should be a definitive proof of the gene translation and protein existence. Therefore, the question still remains: are transposable elements really likely to contribute to the diversity of our proteome? By searching the PDB database, we found evidence suggesting that some transposable elements (LINEs and LTRs) can contribute to our proteomes, while others (Alus) are rather "unsuitable" for this purpose. Because of the small size of current PDB database (24,248 structures as of February 13, 2004), we only found a few cases of proteins with incorporated transposable elements fragments, but the growth of the database in the future should help us in better understanding the impact of transposable elements on protein diversity.


References:
Caras, I. W., M. A. Davitz, et al., 1987. Cloning of decay-accelerating factor suggests novel use of splicing to generate two proteins. Nature 325:545-549.
Brosius, J., 1991. Retroposons - seeds of evolution. Science 251:753.
Makalowski, W., 2000. Genomic scrap yard: how genomes utilize all that junk. Gene 259:61-67.
Nekrutenko, A. and W. H. Li, 2001. Transposable elements are found in a large number of human protein-coding genes. Trends Genet. 17:619-21.
Lorenc, A. and W. Makalowski, 2003. Transposable elements and vertebrate protein diversity. Genetica 118:183-91.

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 03/10/04

No Classes - SPRING BREAK

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 03/17/04

Speaker: Dr. Andrzej Konopka, BioLingua Research


Title: "Systems thinking in biology: Pragmatic inference and other principles of integrative modelling."


Abstract: A concept of a system as something opposite to an arbitrary collection of “parts” has been associated with most (if not all) efforts humans devoted to an explanation of the phenomenon of life for over two recent millennia. However a systematic research programme that specifically aimed at methods of systems thinking is known only since 1930s. This conversation is devoted to a review, a survey and a critique of current general methods of data integration from two different perspectives: 1) logical and 2) relational. As far as logic is concerned a sound distinction needs to be made between the phenomenon to be modelled, its model, and the (biomedical) savant who actually does modelling. [This -so called- epistemic cut is a challenging problem when the terms of modelling and sensitivities of modelers are incompatible with each other in a way that obscures the actual phenomenon to be studied.]  As far as relational principles of clear thinking are concerned one needs to focus on methods that would allow describing objects and relations between them in a interchangeable manner. On the other hand all pragmatic aspects of clear thinking require a relation of order that would enable   principles of causality (everything has its cause) and hierarchical organization (everything is either an ancestor or a descendant of something else). About a third of this conversation will be devoted to specific examples of computational data integration that will illustrate strengths as well as misgivings of general methods of pragmatic inference known to date.


Recommended Reading:
Bertalanffy, von L., 1933. Modern Theories of Development: an Introduction to Theoretical Biology. Oxford: Oxford University Press.
Bertalanffy, von L., 1969. General System Theory: Foundations, Development, Applications. New York: George Braziller.
Konopka, A. K., 2003. Systems biology: aspects related to genomics. In: Cooper DN, ed. Nature Encyclopedia of the Human Genome. Vol. 5. London: Nature Publishing Group Reference, 459-465.
Konopka, A. K., 2002. Grand metaphors of biology in the genome era. Computers & Chemistry 26:397-401.
Konopka, A. K, J. C. Crabbe, 2003. Practical aspects of practicing interdisciplinary science. Computational Biology and Chemistry 27:163-164.
Konopka, A. K., 2002. This is Biology: The science of the living world by Ernst Mayr (Book Review). Computers & Chemistry 26:543-545.
Lewontin, R., 2000. The Triple Helix: Gene Organism and Environment. Cambridge, MA: Harvard University Press.
Lewontin, R., 2001. It Ain't Necessarily So: The Dream of the Human Genome and Other Illusions (2-nd edition). New York: New York Review Books.
Lewontin, R. C., 1996. Evolution as Engineering. In: Collado-Vides J, Smith, T., and Magasanik, B., ed. Integrative Approaches to Molecular Biology. Cambridge, MA: The MIT Press.
Mikulecky, D. C., 2001. Robert Rosen (1934-1998): a snapshot of biology's Newton. Computers & Chemistry 25:317-327.
Mikulecky, D. C., 2001. The emergence of complexity: science coming of age or science growing old? Computers & Chemistry 25:341-348.
Mikulecky, D. C., 2001. Network thermodynamics and complexity: a transition to relational systems theory. Computers & Chemistry 25:369-391.
Pagels, H. R., 1989. The Dreams of Reason : The Computer and the Rise of the Sciences of Complexity. New York: Bantam.
Pattee, H. H., 1969. How does a molecule become a message? In: Lang A, ed. 28th Symposium of the Society of Developmental Biology. New York: Academic Press, 1–16.
Pattee, H. H., 2001. The physics of symbols: bridging the epistemic cut. BioSystems 60:5-21.
Rosen, R., 1991. Life Itself. New York: Columbia University Press.

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 03/24/04

Speaker: Dr. Laura Elnitski, Dept. of Biology, Penn State University


Title: "Evolutionary conservation of exonic splicing enhancer motifs and alternative splicing patterns in whole genome human-mouse-rat alignments."

 
Abstract: It is well established that many exons contain internal sequences that can enhance or repress splicing. We have mapped binding sites for splicing enhancer machinery on the human-mouse-rat whole genome alignments for the purpose of identifying potential exonic splicing enhancers (ESEs)
conserved across the three species. In this approach, specific binding matrices for 4 ESE motifs, SF2/ASF, SC35, SRp40, and SRp55 [1] were mapped to exons annotated in the April 2003 freeze of the Human Genome Browser (http://genome.ucsc.edu/). Of the nearly 5 million conserved binding motifs predicted genome wide, 775,000 intersect with exons. Additionally, we identified alternative splicing events in human, mouse and rat gene orthologues using sim4 [2] alignments of the cDNA
 sequences in the RefSeq and dbEST databases (http://www.ncbi.nlm.nih.gov) with the human or rodent genomic sequences. We report the correlation between the distribution of conserved ESE
motifs and alternatively spliced exons. Furthermore, we provide a queriable resource that integrates predicted ESE regions and single nucleotide polymorphisms or other sequence features through our database called GALA, Genomic Alignments and Annotations [3] which could assist in the
identification of altered splicing patterns associated with human disease.


References:
Cartegni, L., J. Wang, Z. Zhu, M. Q. Zhang, and A. R. Krainer, 2003. ESEfinder: a web resource to identify exonic splicing enhancers, Nucleic Acid Research 31:3568-3571.
Florea, L., G. Hartzell, Z. Zhang, G. M. Rubin, and W. Miller, 1998. A computer program for aligning a cDNA sequence with a genomic DNA sequence, Genome Res. 8:967-974.
Giardine, B., L. Elnitski, C. Riemer, I. Makalowska, S. Schwartz, W. Miller, and R. C. Hardison, 2003.  GALA, a database for genomic sequence alignments and annotations, Genome Res. 4:732-41.

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 03/31/04

Speaker: Wen-Ya Ko, Dept. of Biology, Penn State University


Title: "Lineage-specific patterns of molecular evolution in the Drosophila melanogaster species subgroup."


Abstract: Translational selection at silent sites is well established in many species.  Under the selection-mutation-drift model, the evolutionary dynamics between major (preferred) and nonmajor (unpreferred) codons is determined by the selection force favoring major codons and the mutational pressure changing major codons back to nonmajor codons.  Based on this model, we studied the lineage-specific patterns of codon usage in six D. melanogaster subgroup species (D, melanogaster, D. simulans, D, teissieri, D. yakuba, D. erecta, and D. orena) and two ancestral lineages (D. teissieri-D. yakuba and D. erecta-D. orena).  From the result of 20 nuclear genes (9515 codons), four of the eight lineages had a codon usage pattern biased toward unpreferred substitutions.  When each gene was analyzed separately, this trend was also observed in most of the genes in each of the four lineages.  A significant excess of preferred substitutions was observed in one lineage although the trend was less consistent among the genes.  The patterns of the other three lineages remain uncertain due to the lack of a consistent trend in individual genes.  This may indicate that these three lineages are not significantly departed from the equilibrium.  From pairwise comparisons of the patterns of silent and protein evolutions between sister species pairs, D. melanogaster has more unpreferred silent substitutions and faster rates of protein evolution than its sister species, D. simulans.  Studies of major codon usage patterns in a species would help understand the major cause of protein evolution if a genome-wide biased codon usage pattern reflects the demographic history that changes selection intensities.  Future studies will focus on distinguishing the roles of selection and mutational bias at silent sites and on establishing the patterns of protein evolution in other sister species pairs.


References:
Akashi, H., 1995. Inferring weak selection from patterns of polymorphism and divergence at "silent" sites in Drosophila DNA. Genetics 139:1067-1076.
Akashi, H., 1996. Molecular evolution between Drosophila melanogaster and D. simulans: reduced codon bias, faster rates of amino acid substitution, and larger proteins in D. melanogaster. Genetics 144:1297-1307.
Akashi, H. and S. W. Schaeffer, 1997. Natural selection and the frequency distributions of "silent" DNA polymorphism in Drosophila. Genetics 146:295-307.
Begun, D. J. and P. Whitley, 2002. Molecular population genetics of Xdh and the evolution of base composition in Drosophila. Genetics 162:1725-1735.
Rodriguez-Trelles, F., R. Tarrio, and F. J. Ayala, 2000. Fluctuating mutation bias and the evolution of base composition in Drosophila. J. Mol. Evol. 50:1-10.

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 04/07/04

Speaker: Dr. Anton Nekrutenko, Dept. of Biochemistry and Molecular Biology, Penn State University


Title: "One gene - two proteins."


Abstract: Although genes have been identified for a large number of human congenital disorders, it is often difficult to pinpoint the exact molecular mechanism of a disease. In some cases the cause of the disorder may not be easily discernable because it lies beyond accepted concepts of molecular biology. One such concept is that each mammalian gene is thought to encode a protein in just one reading frame. As a result, if a gene contains an alternative (out of phase) reading frame (ARF) in addition to the canonical coding region, this information is treated as erroneous and almost never included in genetic databases.  Thus, it is unavailable to researchers studying a gene linked to a particular disorder. However, ARFs can be translated and their disruption may lead to severe clinical manifestations! A remarkable example of a human gene encoding two proteins in different reading frames is XLas ­ the extra long form of the G-protein a-subunit. This gene contains an ~1,000 bp ARF nested within the original coding region. The ARF has the same orientation as the original coding region but encodes a protein in a different phase (+1). This arrangement is conserved in XLas genes from other mammals including mouse, rat and dog. The resulting mRNA is translated into two proteins that share no sequence similarity. Interestingly, the two proteins interact with each other. Disruption of this interaction is linked to a series of phenotypic effects that include mental retardation and growth deficiency. 
TheXLas exampleprompts fundamental questions that have never been studied on a genome-wide scale before: Are there other human genes containing ARFs? Is there an evidence for a “hidden proteome” consisting of previously undetected ARF-encoded polypeptides? The answer appears to be “yes”: in a preliminary study we have identified 81 ARF-containing genes using a strict set of criteria (ARFs must contain³200 codons and be conserved in at least two non-primate mammals). Are there human genetic disorders that may be explained by mutations within ARFs? The 81 genes we have identified are linked to 84 genetic disorders. For example, the disruption of an ARF in the mammalian X-box binding protein-1 is linked to severe liver hypoplasia that results in anemia and in uterodeath. 

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 04/14/04

Speaker: Dr. James Leebens-Mack, Dept. of Biology, Penn State University  


Title: "The Utility of Whole Chloroplast Genome Sequencing for Reconstructing Deep Nodes  within Basal Angiosperms."


Abstract: Most recent molecular phylogenies based on one to several genes have suggested that the monotypic Amborella, or Amborella plus waterlilies, represents the basal, extant angiosperm lineage.  Last year the chloroplast genome of Amborella was sequenced and all 61 protein coding genes shared with 12 other available land plant chloroplast genomes were used to assess its phylogenetic position.  Analyses of both nucleotide and amino acid sequence data placed the monocot lineage, rather than Amborella, at the base of the angiosperms.  We have sequenced five new chloroplast genomes to determine if limited taxon sampling could explain this surprising result. These include two monocots (Acorus and Yucca), a waterlily (Nuphar), a basal eudicot (Ranunculus), and a gymnosperm (Ginkgo).  Phylogenetic analyses of both amino acid and nucleotide sequences provided strong support for the basal position of Amborella, and parametric bootstrap analyses implicated long-branch attraction in the original study.


References:
Goremykin, VV., K. I. Hirsch-Ernst, S. Wolfl, and F. H. Hellwig, 2003.  Analysis of the Amborella trichopoda chloroplast genome sequence suggests that amborella is not a basal angiosperm.  Mol. Biol. Evol. 20(9):1499-505.

Zanis, M. J., D. E. Soltis, P. S. Soltis, S. Mathews, and M. J. Donoghue, 2002.  The root of the angiosperms revisited. Proc. Natl. Acad. Sci. USA 99(10):6848-6853.

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 04/21/04

Dr. Eric Davidson, Dept. of Biology, California Institute of Biology, CA
The Department of Biology announces the
Russell Marker Lectures in Evolutionary Biology:

"Evolution and the Genomic Regulatory
Code for Development"


Wednesday, April 21, 2004 at
8:00 p.m.
Location: Room 101 Thomas Building
Title: “Evolution of Animal Body Plans”
Refreshments to follow.

T
hursday, April 22, 2004 at 12:30 p.m.
Location: Kern Building Auditorium
Title: “Five Hundred Million Years of Echinoderm Evolution: Comparison of Gene Regulatory Architecture in a Sea Urchin and a Starfish

Refreshments to follow.

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 04/28/04

Bioinformations Workshop         Click here for powerpoint slides 
 
Location:  310 Rider II         Time:  12:00 p.m. (Noon)

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