Institute of Molecular
Evolutionary Genetics











Fall 2006


Previous IMEG Seminars and Abstracts:

Fall 2013

Spring 2013

Fall 2012


Spring 2012

Fall 2011

Fall 2010


Spring 2010
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


Speaker and title of seminar


Speaker: Dr. Stephen W. Schaeffer- Department of Biology
Title: Chromosomal Rearrangement during the Evolution of Drosophila Genomes
Abstract: Seven of the 12 Drosophila genomes that have recently been sequenced provide an opportunity to understand the process of chromosomal rearrangement because substantial changes in gene order have taken place.  This talk will focus on the method of linkage chain analysis to infer the number of chromosomal inversion occurring on various Drosophila lineages.  This method examines the information at conserved linkage group boundaries to link breakpoints that have been involved in paracentric inversions.  The distribution of breakpoints within linkage chains provide a more accurate estimate of the total number of inversions that have occurred down different Drosophila lineages.  The use of breakpoint information from outgroup species allows the ancestral states of each inversion breakpoint to be determined between a pair of species.  The ancestral states can then be used to infer the gene order of the common ancestral species.  As an example, a complete linkage chain analysis of the six chromosomes between D. melanogaster and D. pseudoobscura will be presented. The data show that while there is not a significant difference in the rate of rearrangement between the two species, several chromosomes show significant differences in inversion rates.  Simulations of the rearrangement process show that breakpoints are nonrandomly re-used.  I will briefly discuss the implications of genomic comparison data between D. pseudoobscura and D. persimilis to models of chromosomal speciation.



NOOR, M. A., K. L. GRAMS, L. A. BERTUCCI and J. REILAND, 2001 Chromosomal inversions and the reproductive isolation of species. Proc. Natl. Acad. Sci. USA 98: 12084-12088.

PEVZNER, P., and G. TESLER, 2003 Human and mouse genomic sequences reveal extensive breakpoint reuse in mammalian evolution. Proc. Natl. Acad. Sci. USA 100: 7672-7677.

SANKOFF, D., and P. TRINH, 2005 Chromosomal breakpoint reuse in genome sequence rearrangement. J Comput Biol 12: 812-821.


Speaker: Dr. Mark Shriver- Department of Anthropology

Title: The Genetic Architecture of Normal Variation in Human

Pigmentation: An Evolutionary Perspective and Model

Abstract: Skin pigmentation varies substantially across human populations in a manner largely coincident with ultraviolet radiation intensity. This observation suggests that natural selection in response to sunlight is a major force in accounting for pigmentation variability. We review recent progress in identifying the genes controlling this variation with a particular focus on the trait's evolutionary past and the potential role of testing for signatures of selection in aiding the discovery of functionally important genes. We have analyzed SNP data from the International HapMap project in 77 pigmentation candidate genes for such signatures. Based on these results and other similar work, we provide a tentative three population model (West Africa, East Asia and North Europe) of the evolutionary-genetic architecture of human pigmentation. These results suggest a complex evolutionary history with selection acting on different gene targets at different times and places in the human past. Some candidate genes may have been selected in the ancestral human population, others in the 'out of Africa' proto European-Asian

population, while most appear to have selectively evolved solely in either Europeans or East Asians separately despite the pigmentation similarities between these two populations. Selection signatures can

provide important clues to aid gene discovery. However, these should be viewed as complements, rather than replacements of, functional studies including linkage and association analyses, which can directly

refine our understanding of the trait.



Speaker: Dr. Jamie Blair- Plant Pathology - CANCELLED



Speaker: Dr. Helen Piontkivska- Department of Biology -Kent State University
Title: "Host-pathogen interactions and sequence changes: evolution of CTL and

antibody epitopes in Human Immunodeficiency Virus (HIV-1)"
Abstract:  In human immunodeficiency virus (HIV), mutations that escape from cytotoxic T-lymphocyte (CTL) recognition have been documented, and sequence analyses have provided indirect support for the hypothesis that natural selection has favored CTL escape mutants within an infected host. Similarly, neutralization of virus particles by antibodies may also be contributing factor shaping the evolution of the virus. However, the relative contribution of these two aspects of the host immune response to selection on proteins of HIV-1 and related viruses remains unclear. Our analyses of sequence data from the nine protein-coding genes of HIV-1 showed striking differences in evolutionary pattern between epitopes for host neutralizing antibodies (Ab) and epitopes for CTL.  Our results showed that the greatest median amino acid residue diversity was seen at sites that formed part of Ab epitopes, but not of CTL epitopes. By contrast, sites belonging to CTL epitopes but not to Ab epitopes showed reduced median amino acid sequence diversity not only in comparison to sites in Ab epitopes but also in comparison to non-epitope sites. Further, Ab epitopes that did not overlap CTL epitopes showed the highest frequency of comparisons in which the rate of nonsynonymous (amino acid-altering) nucleotide substitution exceeded that of synonymous nucleotide substitution, supporting the hypothesis that much of the diversity at Ab epitopes results from positive selection exerted by the host immune system. Though less frequent than that at Ab epitopes, there was evidence of such selection at certain CTL epitopes as well; and amino acid differences between sister pairs of sequences in CTL epitopes were more likely to be convergent than those in Ab epitopes. The pattern seen at CTL epitopes may represent the result of conflicting pressures favoring conservation of the amino acid sequence for functional reasons and amino acid replacements for reasons of CTL escape.




Speaker: Dr. Cooduvalli Shashikant ~ Dairy and Animal Science Depart.

Title: "Comparative cis-regulatory analysis of a vertebrate Homeobox gene"
Abstract:  The Hoxc8 early enhancer is a 200 bp cis-regulatory region that controls initiation and establishment phase of Hoxc8 expression during mouse embryonic development.  The Hoxc8 early enhancer comprises nearly a dozen elements identified by comparative studies and mutational analysis in transgenic mouse embryos.  Comparative study shows a remarkably plasticity in the Hoxc8 early enhancer activity. Species specific variation in its sequence and elemental composition is reflected in differences in their enhancer activities when assayed in transgenic mouse embryos.  The Hoxc8 early enhancer determines reporter gene expression by two distinct mechanisms.  One that determines tissue-specific expression and a second determines the anterior extent of expression.  Transcription factors that are likely to regulate Hoxc8 expression include members of the Cdx, forkhead, Lef1/Tcf, Smad and Hox families.  Among these, Cdx2 is a strong candidate to regulate Hoxc8 early enhancer activity.  Cdx2 protein can bind to two distinct elements within the enhancer.  Its spatiotemporal expression pattern is consistent with the early phase of Hoxc8 expression. Comparison of Hoxc8 and Cdx2 regulation suggests that they both respond to posteriorizing signals. Furthermore, cis-regulatory analysis of Cdx2 reveals the presence of positive-negative regulatory elements that control Cdx2 expression.  Taken together these studies will present a model for a posterior determination mechanism active during mouse embryonic development.


Shashikant C.S., S.A. Bolanowski, S. Anand, and S.M. Anderson.  Comparisons of diverged vertebrate Hoxc8 early enhancer activities reveal modification of regulatory interactions at conserved cis-acting elements Submitted.


Wang, W.C.H. and C.S. Shashikant.  Evidence for positive and negative regulation of the mouse Cdx2 gene. Submitted.


Shashikant C., S.A. Bolanowski, J. Danke, and C.T. Amemiya.  Hoxc8 early enhancer of the Indonesian coelacanth, Latimeria menadoensisJ.Exp.Zool. Mol.Dev.Evol. 302, 557-563, 2004. 


Wang, C.H.W., S. Anand, D.R. Powell, A.B. Pawashe, C.T. Amimiya, and C.S. Shashikant.  Comparative cis-regulatory analysis identify new elements of the mouse Hoxc8 early enhancer. J.Exp.Zool. Mol.Dev.Evol. 302, 436-445, 2004. 


Speaker: Dr. Kazuhiko Kawasaki - Department of Anthropology
Title: Gene duplication and the evolution of vertebrate skeletal mineralization
Abstract:  The mineralized skeleton is a critical innovation that evolved early in vertebrate history.  The tissues found in dermal skeletons of ancient vertebrates are similar to the dental tissues of modern vertebrates; both consist of a highly mineralized surface hard tissue, enamel or enameloid, more resilient body dentin, and basal bone.  These tissues all form on distinct sets or compositions of protein matrix.  Many genes coding these proteins are evolutionarily related and form the secretory calcium-binding protein (SCPP) gene family.  We hypothesize here the duplication histories of these SCPP genes, and their common ancestors, SPARC and SPARCL1.  At around the same time that Paleozoic jawless vertebrates first evolved mineralized skeleton, SPARCL1 arose from SPARC by whole genome duplication.  Then both before and after the split of ray-finned fish and lobe-finned fish, tandem gene duplication created two types of SCPP genes, each residing on the opposite side of SPARCL1 on the same chromosome.  One type of these genes was subsequently used in surface tissue and the other in body tissue.  In the tetrapod lineage after the divergence from amphibians, these two types of SCPP genes were separated by intrachromosomal rearrangement.  Subsequently, SCPP genes were co-opted for use by milk, saliva, and eggshell.  While new SCPP genes arose by duplication, some old genes were eliminated from the genome.  As a consequence of this birth-and-death process, phenogenetic drift can occur: while mineralized skeleton is maintained by natural selection, the underlying genetic basis has drifted.  The different genes used for mineralized tissues may partly explain the variation of ancient mineralized tissues.  Many SCPP genes present in our genome today arose as redundant genes that survived and diversified through the adaptive evolution of vertebrate mineralization.


Kawasaki, K. and Weiss, K. M. Evolutionary genetics of tissue mineralization: the origin and evolution of the secretory calcium-binding phosphoprotein family.  J. Exp. Zool. (Mol. Dev. Evol.) 306B, 295-316, 2006.


Kawasaki, K., Suzuki, T., and Weiss, K. M.  Phenogenetic drift in evolution: the changing genetic basis of vertebrate teeth.  Proc. Natl. Acad. Sci. USA. 102, 18063-18068, 2005.


Kawasaki, K., Suzuki, T., and Weiss, K. M.  Genetic basis for the evolution of vertebrate mineralized tissue.  Proc. Natl. Acad. Sci. USA. 101, 11356-11361, 2004.


Kawasaki, K. and Weiss, K. M.  Mineralized tissue and vertebrate evolution: The secretory calcium-binding phosphoprotein gene cluster.  Proc. Natl. Acad. Sci. USA. 100, 4060-4065, 2003.


Speaker: Dr. Paula McSteen - Department of Biology
Title: Genetic and hormonal regulation of inflorescence development in maize
Unlike animals, which make organs during embryogenesis, plants make organs throughout their lifetime through the action of meristems. My lab focuses on axillary meristems, which give rise to branches and flowers and therefore play a fundamental role in plant architecture and reproduction. We aim to understand how axillary meristems initiate using maize which is a model system as it produces multiple types of axillary meristem in the inflorescence.

          We have shown that auxin (a plant growth hormone) is required for axillary meristem initiation in maize as treatment of plants with inhibitors of auxin transport blocks initiation of axillary meristems. The phenotype of plants treated with auxin transport inhibitors bears striking resemblance to a large class of mutants in maize, called “barren inflorescence”. We have taken a genetic approach to identify the genes regulating auxin transport and perception by characterizing and cloning the mutants in this class. One of these mutants is barren inflorescence2 (bif2) which makes fewer branches, spikelets and ear shoots due to defects in the initiation of axillary meristems. The bif2 gene encodes a serine/threonine protein kinase which is conserved in monocots and dicots. We are identifying additional genes required for axillary meristem initiation by identifying proteins that interact with BIF2. One of the proteins BIF2 interacts with and phosphorylates is a transcription factor which is specific to monocots. Therefore, although bif2 sequence and expression are conserved between monocots and dicots, at least one of its putative downstream targets may have diverged.


P. McSteen (2006) Branching out: The ramosa pathway and the evolution of grass inflorescence morphology. Plant Cell, 18: 518-522.


P. McSteen, O. Leyser (2005) Shoot branching. Annual Review of Plant Biology, 56: 353-374.



Speaker: Kerr Wall - Department of Biology
Title: Ultrahigh-throughput transcriptome tagging using pyrosequencing technology

Abstract: Over the last year, pyrosequencing technology has been used to sequence

microbial and organelle genomes, as well as small RNA libraries.  A first

study has recently been reported using this same technology to sequence cDNA

libraries. We report results from several plates of pyrosequenced

transcripts from a model plant species, Arabidopsis thaliana, and a

non-model basal eudicot, Eschscholzia californica (California poppy).  We

also discuss the implications of this new technology for transcriptome

sequencing as well as the advantages and disadvantages over traditional

capillary-based cDNA sequencing.


References: Margulies et al (2005).  Genome sequencing in microfabricated high-density

picolitre reactors.  Nature. Sep 15;437(7057):376-80.


Bainbridge et al (2006).  Analysis of the prostate cancer cell line LNCaP

transcriptome using a sequencing-by-synthesis approach.  BMC Genomics. Sep



Moore et al (2006). Rapid and accurate pyrosequencing of angiosperm plastid

genomes.  BMC Plant Biol. Aug 25;6:17.


Goldberg et al (2006).  A Sanger/pyrosequencing hybrid approach for the

generation of high-quality draft assemblies of marine microbial genomes.

PNAS.  Jul 25;103(30):11240-5.


Poinar et al (2006) Metagenomics to paleogenomics: large-scale sequencing of

mammoth DNA. Science. Jan 20;311(5759):392-4.


Lu C et al (2006).  MicroRNAs and other small RNAs enriched in the

Arabidopsis RNA-dependent RNA polymerase-2 mutant.  Genome Res.



Speaker: Dr. Veronica Hinman- Department of Biology, Carnegie Mellon University
Title: Regulatory Gene Network Evolution in Echinoderms
We are undertaking an evolutionary comparison of the gene regulatory network (GRN) architectures that control specification in sea urchin and sea star embryos.  The extensive analysis of a GRN in sea urchins has provided a unique opportunity for a comparative investigation to elucidate mechanism of evolution at this level.  We would like to answer questions such as, which features of a regulatory network are conserved, how are changes incorporated into a GRN, and how do these changes relate to the evolution of morphology?  The sea star Asterina miniata has been developed as an ideal experimental model for this analysis.  Gametes are readily available and gene transfer and perturbation of gene products have been performed.  Sea stars last shared a common ancestor with sea urchins around 500 million years ago, in the Upper Cambrian.  They appear to be at an ideal evolutionary distance for meaningful comparisons since they share many conserved aspects in their development and yet there exist specific morphological differences.  

                 We have previously shown that a common developmental feature of sea star and sea urchin GRNs is the use of an orthologous three gene positive regulatory feedback loop that serves to ‘lock down’ gene expression required for the specification of the endoderm and thus to drive development forward.  The conservation of this feature across the immense period of evolutionary time such as separates these echinoderms demonstrates the indispensable nature of this process in their development.  Several differences were also noted in the GRN architecture.  For example, tbrain (tbr) is incorporated into the endomesoderm-specification network in the sea star while it is involved in skeletal lineage specification in sea urchins.   

                The comparative GRN analysis has been continued by asking how (in terms of GRN reorganization) tbr has been co-opted for use in skeletogenesis in sea urchins.  In this analysis it was shown that the otx gene, although conserved in expression and function, is regulated by Tbr in the sea star but not the sea urchin.  As a logical extension of this work, an extensive comparison of the cis regulatory control module of the otx gene in the two taxa was performed.  We are able to demonstrate how the evolution of function of the tbr gene is encoded in the cis regulatory module of a target gene.  These new data will be discussed.


Larroux, C., Fahey, B., Liubicich, D., Hinman, V. F., Gauthier, M., Gongora, M., Green, K., Worheide, G., Leys, S. P. and Degnan, B. M. (2006)Developmental expression of transcription factor genes in a demosponge: insights into the origin of metazoan multicellularity. Evol. Dev. 8(2):150-173.

 Otim, O., Hinman, V. F., and Davidson, E. H. (2005)Expression of AmHNF6, a sea star orthologues of a transcription factor with multiple distinct roles in sea urchin development. Gene Expr Patterns. 5:381-386.

 Hinman, V. F., Nguyen, A. T., Cameron, R. A. and Davidson, E. H. (2003). Developmental gene regulatory network architecture across 500 million years of echinoderm evolution. Proc Natl Acad Sci U S A 100, 13356-61.


Speaker: Dr. Masafumi Nozawa - Department of Biology
Title: Evolutionary stability of the number and the repertoire of olfactory receptor genes in Drosophila species
Abstract: Olfactory receptor (OR) genes play an important role in olfaction and are essential for animals to find desirable items and to avoid dangers.  We have identified all OR genes in the draft genome sequences of 12 Drosophila species by bioinformatic methods and investigated their evolutionary dynamics using phylogenetic analysis.  The results have shown that there have been frequent gene gain and loss events during the Drosophila evolution, suggesting birth-and-death evolution.  Many recent gene duplication events occurred in tandem, indicating that unequal crossing over would be a major mechanism for gene duplication.  On the other hand, chromosomal rearrangements and translocations have contributed to establish the genome-wide distribution of OR genes, since the chromosomal positions of orthologous genes were substantially different among distantly related species.  In spite of these gene gain and loss events, all species examined have a similar number (51-66 genes) and repertoire of functional OR genes.  Estimating the numbers of OR genes in ancestors for these species, we found that the ancestral species also had similar numbers of OR genes compared to the extant species.  In addition, all clades defined in a phylogenetic tree already existed in the ancestral species.  These results suggest that the number and the repertoire of OR genes have been stable during the Drosophila evolution, which is in contrast to the evolutionary dynamics of the mammalian OR genes.  Mechanisms that keep the number and the repertoire of Drosophila OR genes small and stable will be discussed.


Niimura, Y., and M. Nei. 2005. Evolutionary dynamics of olfactory receptor genes in fishes and tetrapods. Proc. Natl. Acad. Sci. USA 102: 6039-6044.

Robertson, H. M., and K. W. Wanner. 2006. The chemoreceptor superfamily in the honey bee Apis mellifera: expansion of the odorant, but not gustatory, receptor family. Genome Res. 16 In press.


Speaker: Dan Hartl- Higgins Professor of Biology Harvard University -Marker Lecture

              8:00 PM 104 Keller Bldg.
Title: Overwhelming odds against the less fit: Evidence for positive selection in protein evolution.
Abstract:  Short description: Analysis of DNA sequence variation within and between species confirms that many amino acid polymorphisms are deleterious, that some deleterious polymorphisms can become fixed, but that the majority of amino acid replacements are probably driven by weak positive selection. Some explanations are suggested.



Speaker: Dan Hartl- Higgins Professor of Biology Harvard University- Marker Lecture

             12:00 PM 117 HUB Auditorium

Title: Transcriptional variation and plasticity in the yeast genome.

Abstract: Transcriptional plasticity refers to changes in the level of transcription that take place in response to changes in the environment. Although a great deal is known about the transcriptome of laboratory yeast (S. cerevisiae) and its response to environmental changes, relatively little is known about either transcriptional plasticity or GEI for transcriptional plasticity among genetically diverse natural isolates. We have studied genome-wide patterns of gene expression in six natural isolates grown in each of four different environments representing a continuum of rich and poor nutritional conditions. We have also identified a single-gene difference segregating in natural populations that is associated with increase in transcription of about 150 genes and a decrease in transcription of about 200 genes. Evidence is presented that the polymorphism responsible for these manifold physiological effects is in a gene that encodes a major sensor of the external nutritional environment.






Speaker: Yogeshwar Kelkar - Department of Biology
Title: Factors affecting microsatellite mutability inferred from human-chimpanzee genomic alignments
Abstract:  Microsatellites, tandemly repeated nucleotide sequences of small motifs (1-6 bp), are ubiquitous in eukaryotic genomes. They undergo rapid change in their length due to insertion or deletion of one or multiple basic repeat units. Though these repeats are simple, their mutational mechanism is not very well understood. Microsatellite mutations take place at very high rates, as high as 10-4 to 10-3 mutational events per cell per replication in humans. Some of these repeats are very unstable and responsible for more than 40 known neurological, neurodegenerative, and neuromuscular disorders; though only certain trinucleotide repeats are responsible for most of these disorders.

          It is now widely accepted that number of repeats in a microsatellite is an important determinant of mutation rate in the sense that longer microsatellites mutate faster, although there is no clear consensus over the exact manner in which length affects microsatellites. Also, the motif that makes up a microsatellite determines mutability of microsatellite to a large extent.

          There is a lot of variation in mutability of microsatellites. It has been experimentally shown that two similar microsatellites can mutate at very different rates if the context of their flanking sequences is changed. Clearly, microsatellite mutation process is a function of inherent sequence properties, local as well as of large-scale genomic factors. A comprehensive model that incorporates all known factors affecting microsatellite mutability is needed. Here we are trying to correlate various local genomic factors around microsatellites, with the mutability of microsatellites, as well as to estimate the degree to which microsatellite length and motif are important in determining microsatellite mutability.


Webster, M.T., N.G. Smith, and H. Ellegren, Microsatellite evolution inferred from human-chimpanzee genomic sequence alignments. Proc Natl Acad Sci U S A, 2002. 99(13): p. 8748-53.   


Speaker: Dimitria Chalkia - Department of Biology - CANCELLED