IMEG

Institute of Molecular
Evolutionary Genetics

 
 
 
          
 

IMEG SEMINARS
Fall 2005
 
Previous IMEG Seminars and Abstracts:

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

Spring 2002

 Date Speaker and title of seminar

 08/31/05

NO CLASS

 09/07/05 Speaker: Dr. Horoshi Akashi - Department of Biology
Title: Molecular evolution in the Drosophila melanogaster species subgroup:
Frequent parameter fluctuations on the time-scale of molecular divergence

Abstract: Although mutation, genetic drift, and natural selection are well-established as determinants of genome evolution, the importance (frequency and magnitude) of parameter fluctuations in molecular evolution is less understood.  DNA sequence comparisons among closely related species allow specific substitutions to be assigned to lineages on a phylogenetic tree.  In this study, we compare patterns of codon usage and protein evolution in 22 genes (>11,000 codons) among Drosophila melanogaster and five relatives within the D. melanogaster subgroup.  We employ a maximum likelihood approach to infer ancestral states and assign changes to eight lineages.  Four of the eight lineages show potentially genome-wide departures from equilibrium synonymous codon usage; three are decreasing and one is increasing in major codon usage.  Several of these departures are consistent with lineage-specific changes in selection intensity (selection coefficients scaled to effective population size) at silent sites.  Intron base composition and rates and patterns of protein evolution are also heterogeneous among these lineages.  The magnitude of forces governing silent, intron, and protein evolution appear to have varied frequently, and in a lineage-specific manner, within the D. melanogaster subgroup. Establishing the mechanisms underlying these patterns will be critical for interpreting tests of adaptive protein evolution that rely on contrasts between silent and replacement changes. 

References:
Ko, W.Y., R. David, and H. Akashi, 2003 Molecular phylogeny of the Drosophila melanogaster species subgroup. Journal of Molecular Evolution 57: 562-573.

Akashi,  H., 2001  Gene expression and molecular evolution. Current Opinions in Genetics and Development 11: 660-666.

Akashi, H. 1995  Inferring weak selection from patterns of polymorphism and divergence at "silent" sites in Drosophila DNA. Genetics 139: 1067-1076.

 09/14/05 Speaker: Dr. Will Provine - Cornell University
Title: Random genetic drift: A reassessment in historical perspective
Abstract: 
Provine will first argue that the "evolutionary synthesis" is a poor guide in modern evolutionary biology, and then address Sewall Wright's use of the concept of random genetic drift in his view of the evolutionary process. Wright always saw random drift and inbreeding as basically the same thing. Provine will attempt to distinguish random genetic drift from inbreeding, founder effects, and small effective population size. An assessment follows of the foundation studies of random drift in the mid-1950s by Wright and Kerr, Kerr and Wright, Buri, Crow and Morton, and Dobzhansky and Pavlovsky.

The second half of the talk is devoted to the role of random drift in deep evolutionary time, namely in the theories of neutral molecular evolution. Provine will argue that summarizing the neutral theories as the "neutral mutation-random drift hypothesis" is inadequate.  Neutral molecular evolution remains the most surprising, important, and robust development in evolutionary biology since the "evolutionary synthesis," whether or not movement of selectively neutral mutations is determined by random drift, hitchhiking, or other means of movement.

 09/21/05 Speaker: Dr. Yoshihito Niimura - Tokyo Medical and Dental University, Tokyo, Japan
Title: Evolutionary Dynamics of Vertebrate Olfactory Receptor Genes
Abstract: 
Vertebrates can discriminate among thousands of different odor molecules in the environment. Odor molecules are detected by olfactory receptors (ORs), which form the largest known multigene family in vertebrates. To understand the evolutionary dynamics of OR genes, we have conducted a phylogenetic analysis of all functional genes identified from the genome sequences of zebrafish, pufferfish, frogs, chickens, humans, and mice. The results suggested that the most recent common ancestor between fishes and tetrapods had at least nine ancestral OR genes, and all OR genes identified were classified into nine groups each of which originated from one ancestral gene. Eight out of the nine group genes are still observed in current fish species, while only two group (a and g) genes were found from mammalian or avian genomes with a few exceptions. In mammals or birds, group g genes expanded enormously, containing ~90% of the entire gene family. Group a and g genes are nearly absent in fishes, while four major group genes present in fishes are completely absent in mammals or birds. The expansion of group g genes has also occurred in frogs, but frogs retain the group genes that are abundant in fishes, indicating that the frog OR gene family has both mammal-like and fish-like characters. These observations can be explained by the environmental change that organisms have experienced after the divergence between fishes and tetrapods. In the tetrapod lineage, repeated gene duplications and massive gene losses appear to have occurred to adapt in the terrestrial environment, whereas the change in OR gene repertoire in the fish lineage seems smaller than that in the tetrapod lineage, reflecting a smaller environmental change from the common ancestor.
References:
Niimura, Y. and Nei, M. (2003) Evolution of olfactory receptor genes in the human genome. Proc. Natl. Acad. Sci. USA 100: 12235–12240.

Niimura, Y. and Nei, M. (2005) Comparative evolutionary analysis of olfactory receptor gene clusters between humans and mice. Gene 346: 13–21.

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

 09/28/05 Speaker: Li Hao - Department of Biology
Title:  Comparative genomics and evolutionary analysis of natural kill cell receptor gene complex
Abstract: 
The natural killer (NK) receptor gene complex (NKC) encodes a large number of C-type lectin receptors which are expressed on NK cells and other immune-related cells. These lectin-type NK cell receptors play an important function in regulating NK-cell cytolytic activity and subsequently protect cells against virus infection and tumorigenesis. To understand evolutionary dynamics of these lectin genes in NKC, we characterized the entire NKC gene structures from humans, mice, rats, and dogs and then conducted phylogenetic analysis of all putative functional genes. Results show that the number of genes in NKC of rodents is twice more than that of humans and dogs, which is mainly due to rodent-specific expansion of certain gene families, including Klra and Ocil, etc. The entire NKC can be divided into 4 smaller genomic clusters (A~D). The birth-and-death rates of the gene families among different genomic clusters are different, in which the cluster C contains more or less the similar number of genes among species, whereas the cluster B and D show a trend of rodent-specific expansion. To investigate the origin of these NKC genes, we also searched the putative NKC sequences from cattle, opossum, and chicken genomes. The results indicate that the expansion of the NKC gene families might have occurred before the separation of placental and marsupial mammals but after the divergence between birds and mammals.
References:

Kelley, J., L. Walter, and Trowsdale. 2005. Comparative genomics of natural killer cell receptor gene clusters.  PLoS Genetics 1:129-139.


 10/05/05 Speaker: Dr. Eddie Holmes - Department of Biology
Title: The Evolutionary Genetics of RNA viruses
Abstract: 
RNA viruses are of great biological importance because of their role as agents of disease.  Herein I will discuss the mechanisms of evolution in RNA viruses in general and then explore how they relate to one important emerging pathogen in particular.  I will begin by examining the key mechanisms of evolution in RNA viruses; mutation (especially the frequency of deleterious mutation), natural selection (including epistasis and immunodynamics), recombination (including reassortment and true RNA recombination) and population size (particularly population bottlenecks at transmission).  I will argue that the rate of deleterious mutation is so great that it acts as a major adaptive constraint and that this may have a major effect on emergibiility, although long-term population sizes may be sufficiently large to avoid fitness losses.  I will then discuss the evolutionary genetics of dengue virus (DENV) in particular.  By examining the evolution of DENV in a variety of epidemiological contexts I will show that deleterious mutations are also commonplace in this virus and may survive in the long-term by a process of complementation.  I will also argue that complex immunodynamics, caused by the co-circulation of multiple serotypes within populations, may also exert a major selective force on this virus.
References:
Moya A, Holmes EC & González-Candelas F. (2004). The population genetics and evolutionary epidemiology of RNA viruses. Nat.Rev.Microbiol. 2, 279-287.

Holmes EC & Twiddy SS. (2003). The origin, emergence and evolutionary genetics of dengue virus. Infect.Genet.Evol. 3, 19-28.

 10/12/05 Speaker: Wen-Ya Ko - Department of Biology
Title: Extreme region-specific heterogeneity in base composition evolution on the Drosophila X chromosome.
Abstract: Fluctuations in base composition have been noted in Drosophila and mammal genomes evolution, but their frequency and genomic breadth, as well as their causes, remain obscure.  Here, we investigated evolution of base composition from fourteen genes located at the telomeric region and nine genes from the non-telomeric regions of X chromosome among Drosophila melanogaster and five of its close relatives.  Substitutions were inferred on each of eight lineages by a maximum likelihood method.  Comparative studies between the two chromosomal regions revealed striking heterogeneities in base composition evolution at the telomeric region in D. yakuba and D. orena.  While AT-increasing synonymous changes were shown in the non-telomeric loci, opposite patterns were found in the telomeric genes in both lineages.  The genomic breadths and magnitudes of changes also differ between these two lineages.  At the telomeric region, loci that show GC-increasing synonymous changes cover a region as large as approximately 1.2 Mb in D. yakuba, but restrict to a much smaller region, approximately 0.13 Mb, in D. orena.  Numbers of AT->GC changes at this small region in D. orena are striking, about 15 folds higher than the numbers of GC->AT changes.  Comparisons of nucleotide substitution patterns between coding and adjacent intronic regions shed some light on the evolutionary mechanisms underlying these patterns.  The GC-increasing patterns of synonymous changes in D. yakuba are less consistent with fluctuations in mutational processes.  On the other hand, neutral mechanism appears to have significant contributions to the GC-increasing patterns found in D. orena.  However, larger magnitudes of GC-increasing silent changes within the coding regions than within the intronic regions suggest contributions of natural selection or biased gene conversion.

References:

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.

Takano-Shimizu, T. 1999. Local recombination and mutation effects on molecular evolution in Drosophila. Genetics 153:1285-1296.

Takano-Shimizu, T. 2001. Local changes in GC/AT substitution biases and in crossover frequencies on Drosophila chromosomes. Mol Biol Evol 18:606-619.


 10/19/05 Speaker: Chiao-Feng Lin - Department of Biology Cancelled
Title: 
Abstract: 

References:

 10/26/05 Speaker: Wen-Yu Chung - Department of Computer Science and Engineering
Title: Rapid and Asymmetric Divergence of Duplicate Genes in the Human Gene Coexpression Network
Abstract: 
Motivation: While gene duplication is known to be one of the most common mechanisms of genome evolution, the fates of genes after duplication are still being debated. In particular, it is presently unknown whether most duplicate genes preserve (or subdivide) the functions of the parental gene or acquire new functions. One aspect of gene function, that is the expression profile in gene
coexpression network, has been largely unexplored for duplicate genes. Results: Here we build a human gene coexpression network using human tissue-specific microarray data and investigate the divergence of duplicate genes in it. The topology of this network is scale-free. Interestingly, our analysis indicates that duplicate genes rapidly lose shared coexpressed partners: after approximately 50 million years since duplication, the two duplicate genes in a pair have only slightly higher number of shared partners as compared with two random singletons. We also show that duplicate gene pairs quickly acquire new coexpressed partners: the average number of partners for a duplicate gene pair is significantly greater than that for a singleton (the latter number can be used as a proxy of the number of partners for a parental singleton gene before duplication). The divergence in gene expression between two duplicates in a pair occurs asymmetrically: one gene usually has more partners than the other one. The network is resilient to both random and degree-based in silico removal of either singletons or duplicate genes. In contrast, the network is especially vulnerable to the removal of highly connected genes when duplicate genes and singletons are considered together. Thus, duplicate genes rapidly diverge in their coexpression profiles in the network and play similar role in maintaining the network robustness as compared with singletons.
References:

Albert, R. and A.L. Barabasi. 2002. Statistical mechanics of complex networks.
Reviews of Modern Physics 74:47-96
Makova, K.D. and W.H. Li. 2003. Divergence in the spatial pattern of gene
expression between human duplicate genes. Genome Res 13:1638-1645
Wagner, A. 2005. Distributed robustness versus redundancy as causes of
mutational robustness. Bioessays 27:176-1
88


 11/02/05 Speaker:  Chiao-Feng Lin  - Department of Biology
Title: Evolution of Minor (U12) Type of Introns
Abstract: 
Two analogous pathways (U2- and U12-dependent) for the splicing of pre-mRNAs are found in many higher eukaryotes, including human, mouse, fruit fly and /Arabidopsis/. But the U12-dependent pathway seems to be missing in yeast and nematode. The minor type of intron is referred to as U12 because these introns are rare and are removed by a much less abundant splicing complex containing U12 rather than U2 snRNA. U12 introns possess two highly conserved motifs (5’ Splice Site and Branch Point Site) that allow us to determine, in silico, whether an intron is of the U12-type or U2-type. It is proposed that very stringent requirement of 5’SS and BPS signals made U12 introns much more susceptible to mutations. Disruption of splicing signals may convert a U12 intron to a U2 intron, while conversion of a U2 intron to a U12 intron is much less likely. Thus, U12-introns tend to be lost from a genome (1). Two genome-wide studies - in human (2) and /Arabidopsis/ (3) - showed that frequencies of U12 introns are significantly different in the two species. However, variation in the frequency of U12 introns among lineages has never been investigated. In this study, using a comparative genomics and phylogenetic approach, we scanned seven complete genomes (/Arabidopsis/, rice, human, mouse, rat, pufferfish, and fruit fly) for U12 introns. Phylogenetic analysis of U12-containing genes enabled us to identify patterns of evolutionary conservation of U12 introns.

References:

1. Burge CB, Padgett RA, Sharp PA 1998. Evolutionary fates and origins of U12-type introns. /Mol Cell/ 1998 Dec; 2(6):773-85
2. Levine, A. and R. Durbin (2001). A computational scan for U12-dependent introns in the human genome sequence. /Nucl. Acids Res/ 29(19): 4006-4013.
3. Zhu, W. and V. Brendel 2003. Identification, characterization and molecular phylogeny of U12-dependent introns in the Arabidopsis thaliana genome. /Nucl. Acids. Res/ 31(15): 4561-4572.


 11/09/05 Speaker: Zhenguo Lin - Department of Biology
Title: Phylogenetic Analyses of RecA/RAD51-like Gene Family
Abstract:  
DNA repair and homologous recombination are critical for cell viability, genome stability and creating genetic diversity. Recombinase RecA/RAD51 family proteins have been found in all cellular organisms and play critical rules in DNA repair and homologous recombination. Multiple members of RecA/RAD51 family have been identified in Archaea (RADA, RADB) and Eukaryota (RAD51, RAD51B, RAD51C, RAD51D, DMC1, XRCC3 and XRCC2, RecA). We performed extensive phylogenetic analyses using RecA/RAD51-like protein sequences and proposed a hypothesis about evolutionary relationships of RecA/RAD51 gene family. Our results demonstrate that all the members of eukaryotic RAD51 like genes were diverged from a common ancestor by ancient gene duplication events. The first gene duplication event occurred before divergence of Archaea and Eukaryota to producing two major subfamilies: Type A including RAD51, DMC1, RADA and Type B including RADB, RAD51C, RAD51B, RAD51D, XRCC2 and XRCC3. Type A proteins play central roles in DNA repair and homologous recombination while Type B proteins, which form different complexes, play supporting rules of RAD51/DMC1 and develop other functions in other processes. Multiple bacteria RecA like genes found in eukaryotic genomes were probably originated from eubacterial endosymbionts by horizontal gene transfer through the endosymbiosis events of chloroplasts and mitochondria. 

References:

Thacker, J. (1999). "A surfeit of RAD51-like genes?" Trends Genet 15(5): 166-8.
Bleuyard, J. Y., M. E. Gallego, et al. (2005). "Differing requirements for the Arabidopsis Rad51 paralogs in meiosis and DNA repair." Plant J 41(4): 533-45.
Masson, J. Y., M. C. Tarsounas, et al. (2001). "Identification and purification of two distinct complexes containing the five RAD51 paralogs." Genes Dev 15(24): 3296-307.


 


 11/16/05 Speaker: Dr. Zhi-Chun Lai - Department of Biology
Title: Growth Inhibition and Tumor Suppression by a Mob Family Protein, Mats"
Abstract:
We have discovered a novel tumor suppressor, Mats, which determines cell number and tissue growth through restricting cell proliferation and promoting apoptosis in Drosophila.  Our genetic and biochemical studies revealed that Mats functions as an activating subunit of another tumor suppressor, Wts protein kinase.  Mats orthologs exist in plants and animals, and Mats-mediated growth inhibition is likely conserved in humans.  Moreover, we have evidence to show that Mats is a key component of Hippo growth inhibitory and tumor suppression pathway.  Thus, this work extends our understanding of tissue growth and cell number control during development and tumorigenesis, and raises the possibility that Mats-dependent growth inhibition and tumor suppression may have important implications for the understanding and treatment of human cancers.


References:

Lai, Z.-C. Wei, X., Shimizu, T., Ramos, E., Rohrbaugh, M., Nikolaidis, N., Ho, L.-L., and Li, Y. (2005). Control of cell proliferation and apoptosis by Mob as tumor suppressor, Mats. Cell 120: 675-685.


 11/23/05 No Classes - THANKSGIVING HOLIDAY

 11/30/05 Speaker: Dr. Teh-hui Kao - Department of Biochemistry and Molecular Biology
Title: S-RNase-Based Self-Incompatibility in Flowering Plants
Abstract:
Self-incompatibility (SI) is an intraspecific reproductive barrier that allows the pistil of many flowering plants to distinguish between self- and non-self pollen.  Self-pollen is rejected whereas non-self pollen is accepted for fertilization.  It is estimated that more than half of the flowering plant species, representing more than 60 families, possess SI.  To date, three different SI mechanisms have been identified from studies of five of the families, and the S-RNase-based SI mechanism is possessed by three of them: the Solanaceae (containing petunia, potato, tobacco, tomato) Scrophulariaceae (containing snap dragon) and Rosaceae (containing almond, apple, cherry).  Here, the highly polymorphic S-locus controls the specificity of SI interactions between pollen and the pistil.  If pollen carries an S-haplotype that matches one of the two S-haplotypes of the pistil, it is recognized as self-pollen and the growth of its tube is inhibited in the style.  The S-locus contains two separate genes: the S-RNase gene, identified in the late 1980s, controls pistil specificity, and the recently identified S-locus F-box (SLF) gene controls pollen specificity.  In this talk, I will focus on our use of Petunia inflata as a model to study the mechanism of S-RNase-based SI.  I will describe how the S-RNase gene and the SLF gene were identified, properties of S-RNase and SLF, and our ongoing effort to study how S-RNase and SLF mediate growth inhibition of self-pollen tubes.
 

References:

 Wang Y, Wang X, McCubbin AG, Kao T-h (2003).  Genetic mapping and molecular characterization of the self-incompatibility (S-) locus in Petunia inflata.  Plant Mol Biol 53: 565-580 Kao T-h, Tsukamoto, T (2004).  The molecular and genetic bases of S-RNase-based self-incompatibility.  Plant Cell 16: S72-83 Sijacic P, Wang X, Skirpan AL, Wang Y, Dowd PE, McCubbin AG, Huang S, Kao T-h (2004). Identification of the pollen determinant of S-RNase-mediated self-incompatibility.  Nature 429: 302-305 Wang Y, Tsukamoto T, Yi K-w, Wang X, Huang S, McCubbin AG, Kao T-h (2004).  Chromosome walking in the Petunia inflata self-incompatibility (S-) locus and gene identification in an 881-kb contig containing S2-RNase.  Plant Mol Biol 54: 727-742

 


 12/07/05 Speaker: Fabia Battistuzzi - Department of Biology
Title: Eukaryote-prokaryote relationships and the origin of eukaryotes
Abstract:
Multiple hypotheses have been proposed in past years for the origin of eukaryotes. Of these the one that has received more evidence and consensus is the symbiotic origin of this domain from eubacterial and archaebacterial lineages. However, the identity of all the symbiotic lineages, and the number of symbiotic events are still unclear. On one hand analyses purely based on similarity of eukaryotic genes versus various prokaryotic lineages have failed to detect a signal significantly stronger than others suggesting that this method may be inadequate to investigate this question. On the other hand phylogenetic analysis show various eukaryote/prokaryote clusters – aside from the expected ones, eukaryote/α-proteobacteria and eukaryote/cyanobacteria – albeit often supported by low bootstrap values. Results from ongoing research will be presented and compared with previous studies.


References:

Esser C, Ahmadinejad N, Wiegand C, Rotte C, Sebastiani F, Gelius-Dietrich G, Henze K, Krestmann E, Richly E, Leister D, Bryant D, Steel MA, Lockhart PJ, Penny D, Martin W. (2004) A genome phylogeny for mitochondria among α-proteobacteria and a predominantly eubacterial ancestry of yeast nuclear genes. Molecular Biology and Evolution, 21: 1643-1660

 


 12/14/05 Speaker: Dimitra Chalkia - Department of Biology
Title: Gestalt Domain Detection Algorithm: a tool for detecting highly diverged functional protein domains
Abstract: 
The plethora of protein sequences, that has been accumulated the last decade, has led to an explosion in the appearance of sequence-based computational methods for protein domain boundary definition. Although these methods by definition do not provide empirical data, they have proven to be one of the most convenient and important tools for understanding the evolution of proteins and their function. A new computational method designated the Gestalt Domain Detection Algorithm (GDDA), which can predict highly divergent functional domains, was recently developed. The innovation of GDDA is that it modifies the query protein sequence by inserting a segment of a consensus domain sequence (seed) at every amino acid position of the query sequence. The modification of the query sequence increases the sensitivity of rps-BLAST, since the seed sequence provides a “constant” alignment initiation sequence allowing BLAST to extend (i.e. ‘filling in the gaps’ hence gestalt) the alignment even between highly divergent sequences. 

I will be presenting results on the predictive ability of the GDDA by using positive controls and on the experimental validation of GDDA predictions in the TEC protein kinases and the TRP Channels.


References:

Altschul,S.F., Madden,T.L., Schaffer,A.A., Zhang,J., Zhang,Z., Miller,W., and Lipman,D.J. (1997). Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389-3402. Marchler-Bauer,A., Panchenko,A.R., Shoemaker,B.A., Thiessen,P.A., Geer,L.Y., and Bryant,S.H. (2002). CDD: a database of conserved domain alignments with links to domain three-dimensional structure. Nucleic Acids Res. 30, 281-283. Patterson,R.L., van Rossum,D.B., Nikolaidis,N., Gill,D.L., and Snyder,S.H. (2005). Phospholipase C-gamma: diverse roles in receptor-mediated calcium signaling. Trends Biochem. Sci. Ponting,C.P. and Russell,R.R. (2002). The natural history of protein domains. Annu. Rev. Biophys. Biomol. Struct. 31, 45-71. Ramsey,S.I., Delling,M., and Clapman,D.E. (2006). An introduction to TPR Channels. Annu. Rev. Physiol. 68, 18.1-18.29 Smith,C.I., Islam,T.C., Mattsson,P.T., Mohamed,A.J., Nore,B.F., and Vihinen,M. (2001). The Tec family of cytoplasmic tyrosine kinases: mammalian Btk, Bmx, Itk, Tec, Txk and homologs in other species. Bioessays 23, 436-446. van Rossum,D.B., Patterson,R.L., Sharma,S., Barrow,R.K., Kornberg,M., Gill,D.L., and Snyder,S.H. (2005). Phospholipase Cgamma1 controls surface expression of TRPC3 through an intermolecular PH domain. Nature 434, 99-104.