IMEG Events Institute of Molecular Evolutionary Genetics

Abstract: The current interest in H5N1 avian influenza virus, and its potential threat to human health, has generated a renewed interest in studies of influenza virus evolution. Here I will show how the study of large amounts of complete genome sequence data has shed light on the key patterns and processes of influenza virus evolution. In particular, I will show that reassortment among human influenza viruses is a far more important process than generally envisaged and may have been important for a number of “antigenic cluster jumps” in H3N2 influenza virus. I will also reveal the evolutionary processes response for the dramatic and global rise in resistance to adamantane drugs that occurred in recent months. Through the intensive study of influenza virus in a single population – New York state from 1995 to 2005 – I will show that rather than being characterized by a single dominant lineage, the viruses present during any season represent a small sample of global genetic diversity, with little antigenic drift occurring over a season. The evolution of influenza A vírus is therefore an episodic process, characterized by occasional selective sweeps.

References:

Holmes EC, Ghedin E, Miller N, Taylor J, Bao Y, St. George K, Grenfell BT, Salzberg SL, Fraser CM, Lipman DJ & Taubenberger JK. (2005). Whole genome analysis of human influenza A virus reveals multiple persistent lineages and reassortment among recent H3N2 viruses. PLoS.Biol. 3(9), e300.

Nelson MI, Simonsen L, Viboud C, Miller MA, Taylor J, St. George K, Griesemer SB, Ghedin E, Sengamalay NA, Spiro DJ, Volkov I, Grenfell BT, Lipman DJ, Taubenberger JK & Holmes EC. (2006). Stochastic processes are key determinants of the short-term evolution of influenza A virus. PLoS Path. 2, e125.

01/24/07

Speaker: Dr. Izabela Makalowska- Department of Life Sciences

Title: "Birth And Death of Gene Overlaps in Vertebrates."

Abstract: Several mechanisms have been proposed to explain gene overlap origination. For instance, Keese and Gibbs suggested that overlapping genes arise as a result of overprinting - a process of generating new genes from preexisting nucleotide sequences. This process supposedly took place after divergence of mammals from birds and overlapping genes represent young, phylogeneticaly restricted genes encoding proteins with diverse functions, and are therefore specialized to the present life-style of the organism in which they are found. Shintani et al. suggested that the overlap between genes ACAT2 (acetyl-Coenzyme A acetyltransferase 2) and TCP1 (t-complex 1) arose during the transition from therapsid reptiles to mammals as a result of translocation accompanied (or followed) by loss of part of 3' URT including polyadenylation signal and adoption of signals from the neighboring gene locus. The ACAT2-TCP1 overlap evolution was placed, similarly as in Keese anf Gibbs hypothesis, after the divergence of mammals from birds. Dahary et al. places the origin of most vertebrate overlaps much earlier. He found that human antisense genes have largely conserved linkage in Fugu which may imply that big fraction of human overlapping genes represents vertebrates' ancestral overlaps. However, our previous study of human and mouse overlapping genes showed that even between much closer related species overlaps are not that well conserved. Here we present results of the comparative analysis of seven vertebrate genomes: human, chimpanzee, mouse, rat, chicken, fugu, and zebrafish. This comparative studies shows that many of the vertebrate gene overlaps are not conserved and are lineage specific. On the other hand, this work reveals new, not published before, cases of genes overlap conservation in vertebrates. We also show new mechanisms of overlapping genes evolution and demonstrate, for the first time, that evolutionary events could not only lead to the new gene overlaps origin but also to the loss of an ancient overlap. Therefore luck of strong overlaps conservation between even closely related species may result not only from the origin of new, lineage specific overlap but also be resulting from the loss of many overlaps in some lineages.
Examples from our studies show that one of the major forces leading to overlaps origin is a development of new splice variant, which could either replace the ancient one or be just an addition to already present variants. In addition, our study emphasizes that in order to fully understand the evolution of overlapping genes one has to work in details on many lineages.

References:Keese PK, Gibbs A: Origins of genes: "big bang" or continuous creation? Proc Natl Acad Sci U S A 1992, 89(20):9489-9493.
Shintani S, O'HUigin C, Toyosawa S, Michalova V, Klein J: Origin of gene overlap: the case of TCP1 and ACAT2. Genetics 1999, 152(2):743-754.

Dahary D, Elroy-Stein O, Sorek R: Naturally occurring antisense: transcriptional leakage or real overlap? Genome Res 2005, 15(3):364-368.
Veeramachaneni V, Makalowski W, Galdzicki M, Sood R, Makalowska I: Mammalian overlapping genes: the comparative perspective. Genome Res 2004, 14(2):280-286.

Zhang Y, Liu XS, Liu QR, Wei L: Genome-wide in silico identification and analysis of cis natural antisense transcripts (cis-NATs) in ten species. Nucleic Acids Res 2006, 34(12):3465-3475.

01/31/07

Speaker: Dr. Wen-Ya Ko- Department of Biology

Title: "Within- and between-species sequence variation in the Drosophila yakuba species complex: adaptive protein evolution on A/T to G/C mutations."

Abstract: Fine-scale investigation of nucleotide changes is critical for studying molecular evolution when the underlying evolutionary parameter(s) fluctuates frequently on a gene tree and/or when patterns and rates of nucleotide changes differ between polymorphism and divergence at terminal lineages. Here, we studied within- and between-species nucleotide variation from 19 loci (4530 codons) in D. yakuba and D. santomea and from 6 loci (1414 codons) in D. teissieri. Analysis of average number of polymorphic mutations per allele showed that each terminal lineage contains a large proportion of polymorphic mutations (0.69, 0.72, and 0.56 for D. teissieri, D. yakuba, and D. santomea, respectively). The results suggest that polymorphic mutations can have pronounced effects on inferring patterns of nucleotide changes in a single-allele analysis where an excess of G/C à A/T polymorphic mutations is observed in each species. Differences in ratios of polymorphism to divergence between protein and different fitness classes of synonymous mutations reveal evidence of adaptive protein evolution for mutations from A/T à G/C, but not for mutations in the reverse direction. Adaptive protein evolution on A/T à G/C mutations possibly relates to selection discriminating a subset of amino acids or codons during the processes of protein synthesis.

References: AKASHI, H., 1999 Within- and between-species DNA sequence variation and the 'footprint' of natural selection. Gene 238: 39-51.
AKASHI, H., W. Y. KO, S. PIAO, A. JOHN, P. GOEL et al., 2006 Molecular evolution in the Drosophila melanogaster species subgroup: frequent parameter fluctuations on the timescale of molecular divergence. Genetics 172: 1711-1726.
FAY, J. C., G. J. WYCKOFF and C. I. WU, 2002 Testing the neutral theory of molecular evolution with genomic data from Drosophila. Nature 415: 1024-1026.
SMITH, N. G., and A. EYRE-WALKER, 2002 Adaptive protein evolution in Drosophila. Nature 415: 1022-1024.

02/07/07

Speaker: Dr. Nikolas Nikolaidis- Department of Biology

Title: "The Land of DANGER: an Ancient Developmental Superfamily."

Abstract: Developmental proteins in general and molecules involved in cell differentiation in particular, play a pivotal role in the origin of animal complexity and diversity. Therefore identifying and characterizing the evolutionary history of such molecules is fundamentally important towards understanding the origin of animal complexity and diversity. We have recently identified a highly divergent developmental protein superfamily (DANGER), which originated before the emergence of animals (~850 million years ago) and experienced major expansion-contraction events during metazoan evolution. Sequence analysis suggests that DANGER proteins diverged via multiple mechanisms, including amino acid substitution, intron gain and/or loss, and recombination. Divergence for DANGER proteins is substantially greater than for the prototypic member of the superfamily (Mab-21 family) and other developmental protein families (e.g., WNT proteins). DANGER proteins are widely expressed and display species-dependent tissue expression patterns, with many members having roles in development. A member of this superfamily, DANGER1A, promotes the differentiation and outgrowth of neuronal processes. Regulation of development may be a universal function of DANGER family members. This family provides a model system to investigate how rapid protein divergence contributes to morphological complexity.

References:

Chow KL, Hall DH, Emmons SW (1995) The mab-21 gene of Caenorhabditis elegans encodes a novel protein required for choice of alternate cell fates. Development 121: 3615-3626.

Davidson EH, Erwin DH (2006) Gene regulatory networks and the evolution of animal body plans. Science 311: 796-800.

Kusserow A, Pang K, Sturm C, Hrouda M, Lentfer J et al. (2005) Unexpected complexity of the Wnt gene family in a sea anemone. Nature 433: 156-160.

Nikolaidis N, D Chalkia, DN Watkins, RK Barrow, SH Snyder, van Rossum DB, RL Patterson. Ancient origin of a new developmental superfamily DANGER. Plos ONE in press.

Technau U, Rudd S, Maxwell P, Gordon PM, Saina M et al. (2005) Maintenance of ancestral complexity and non-metazoan genes in two basal cnidarians. Trends Genet 21: 633-639.

van Rossum DB, Patterson RL, Cheung KH, Barrow RK, Syrovatkina V et al. (2006) DANGER, a novel regulatory protein of inositol 1,4,5-trisphosphate-receptor activity. J Biol Chem 281: 37111-37116.

02/14/07

Speaker: Fabia Battistuzzi- Department of Biology-CANCELLED

Title: "Expanding the phylogeny and timing of prokaryotes."

Abstract: Genome sequences of Eubacteria and Archaebacteria have proven informative for the higher-level phylogeny and timing of these organisms that dominated the biology of the early Earth. As this tree of prokaryotes continues to grow with additional sequences, it is possible to better understand how life coevolved with the planetary environment. However, the chronological patterns and metabolic innovations of prokaryote evolution ultimately rely on the phylogeny of these groups, phylogeny that has proved challenging to define. Results from the comparison of multiple phylogenetic trees (ML and distance methods for amino acids and nucleotides data sets) suggest the presence of super-class prokaryote groups, sub-class clusters, and classes that show a problematic phylogenetic placement, leading to a partially resolved consensus tree. They also show a consistent pattern of short internal branches that might have consequences not only for the branching order but also the time estimation of the major classes.

References: Ciccarelli, F.D. et al. Toward automatic reconstruction of a highly resolved tree of life. Science 311, 1283-1287 (2006).

02/21/07

Speaker: Dr. Hong Ma- Department of Biology

Title: "Highly variable patterns of gene duplications in eukaryotic gene family evolution: possible mechanisms and functional implications."

Abstract: Gene duplication is an important means of gene family evolution, particularly in the birth-and-death model of gene family evolution. We have examined the evolution of multiple gene families in eukaryotes and uncovered a wide range of patterns of gene duplications. Some gene families have very stable gene numbers over most, if not all, of the eukarytic history; many gene families have experienced moderate gene duplication rates. In addition, some gene families have had very high rates of gene births in land plants, particularly flowering plants. It has been proposed that both animals and plants, as well as some fungi, have had large-scale genome duplication(s) during their evolutionary history. If we accept this theory, then the families that maintain stable gene number must eliminate duplicates shortly after their birth. Conversely, the births in some gene families can be explained by large-scale genone duplications. The gene families with very rapid birth rates can be explained by additional mechanisms such as tanden duplications and retro-transpositions. It is possible that the functions of different genes can affect the fate of duplicated genes, and the differential survival of the duplicates in turn facilitate the evolution of specific characteristics. The effects of other factors on gene family evolution is also discussed.

References: Hongzhi K, Leebens-Mack J, Weimin N, dePamphilis C W and Ma H. (2004) Highly Heterogeneous Rates of Evolution in the SKP1 Gene Family in Plants and Animals: Functional and Evolutionary Implications. Mol Biol Evol 21(1):117–128.

Zahn L M, Leebens-Mack J, DePamphilis C W, Ma H, and Theissen G. (2005) To B or Not to B a Flower: The Role of DEFICIENS and GLOBOSA Orthologs in the Evolution of the Angiosperms. J Here 96(3):225–240. Lin Z, Kong H, Nei M, Ma H. (2006). Origin and evolution of the recA/RAD51 gene family: Evidence for ancient gene duplication and endosymbiotic gene transfer. Proc Natl Acad Sci USA, 103:10328-10333.

02/28/07

Speaker: Richard Meisel- Department of Biology

Title: "On the Origin and Evolution of Segmentally Duplicated Genes in the Drosophila pseudoobscura Genome."

Abstract: Gene duplication has been recognized as an important evolutionary force for over three decades. The 12 sequenced Drosophila genomes offer an excellent opportunity to study genome evolution, including gene duplication. We identified recently duplicated genes in the Drosophila pseudoobscura genome that arose via segmental duplication after the divergence of D. pseudoobscura and D. melanogaster. The relative orientations of paralogs, lengths of duplicated regions, and sequences flanking duplicated regions provide insights into the molecular mechanisms underlying segmental duplication in Drosophila genomes. To gain a better understanding of the early evolution of duplicated genes, we analyzed nucleotide and protein coding sequence divergence between paralogs. I will present the results of these analyses of recently segmentally duplicated genes in the D. pseudoobscura genome.

References: Moore and Purugganan. 2003. The early stages of duplicate gene evolution. PNAS 100:15682-25687.Richards, et al. 2005. Comparative genome sequencing of Drosophila pseudoobscura: chromosomal, gene, and cis-element evolution. Genome Res. 15:1-18.

03/07/07

Speaker: Erika Kvikstad -Department of Biology

Title: "A macaque’s-eye view of human insertions and deletions: regional rate variation and mechanisms of mutagenesis."

Abstract: Insertions and deletions (indels) cause numerous genetic diseases and lead to pronounced evolutionary differences among genomes. The macaque sequences provide an opportunity to gain insights into the mechanism of these mutations on a genome-wide scale by establishing the polarity of indels occurring in the human lineage since its divergence from the chimpanzee. Here we apply multiple regression analyses to demonstrate an extensive regional indel rate variation stemming from local fluctuations in male and female recombination rates, divergence, proximity to telomere, and other genomic factors. We find that both replication and, surprisingly, recombination contribute significantly to small indel formation. As the relative input of these factors differs between insertions and deletions, the two types of mutations are likely guided in part by distinct mechanisms. These results bring us closer to unraveling the processes of indel mutagenesis.

References: Hellmann I, Prufer K, Ji H, Zody MC, Paabo S, Ptak SE.

Why do human diversity levels vary at a megabase scale?

Genome Res. 2005 Sep;15(9):1222-31.

03/14/07

Speaker: SPRING BREAK - NO SEMINAR

03/21/07

Speaker: Samir Wadhawan -Department of Biology

Title: "Dual Coding, Duplication, Imprinting, and Exon Shuffling Unite to Shape the Evolution of GNAS/GNAL Complex."

Abstract:Gnas and its paralog Gnal constitute the Gs family of G-proteins that encodes the G-protein alpha subunit. The two loci are imprinted and share significant structural resemblance. But a unique feature distinguishing them is the presence of functional protein-coding regions in Gnas that overlap for over 1,000 nucleotides. The two reading frames are embedded in a large paternally transcribed (~2kb in size) upstream exon known as the XL. Shifted one nucleotide relative to each other, the two frames when translated code for XLαs and ALEX proteins. XLαs represents the extra large form of the stimulatory G-protein alpha subunit. ALEX appears to regulate signal transduction properties of XLαs by binding to XLαs and preventing its association with receptors. The XL exon, which encodes both proteins, evolves so rapidly that it is virtually unalignable between primates and rodents. Even within the rodents it is highly divergent. Despite showing so much divergence, the +1 reading frame encoding ALEX is still preserved in these species. Here we characterize the evolution of this exon by sequencing it in several rodents, and analyzing the sequences together with those available for other mammals from various genome assemblies. In addition we decipher the selection constraints acting on other coding regions at both loci and also analyze the evolution of the Gs family.

References:

1. Nekrutenko, A., S. Wadhawan, et al. (2005). "Oscillating evolution of a mammalian locus with overlapping reading frames: an XLalphas/ALEX relay." PLoS Genet 1(2): e18.

2. Klemke, M., R. H. Kehlenbach, et al. (2001). "Two overlapping reading frames in a single exon encode interacting proteins--a novel way of gene usage." Embo J 20(14): 3849-60.

3. Freson, K., J. Jaeken, et al. (2003). "Functional polymorphisms in the paternally expressed XLalphas and its cofactor ALEX decrease their mutual interaction and enhance receptor-mediated cAMP formation." Hum Mol Genet 12(10): 1121-30.

4. Corradi, J. P., V. Ravyn, et al. (2005). "Alternative transcripts and evidence of imprinting of GNAL on 18p11.2." Mol Psychiatry 10(11): 1017-25.

03/28/07

Speaker: Dr. Hiroshi Akashi- Department of Biology

Title: "Genome evolution in the Drosophila melanogaster subgroup: Lineage effects and the time-scale of parameter fluctuations."

Abstract: Recently sequenced genomes of close relatives of Drosophila melanogaster allow investigation of the frequency, magnitude, and genomic breadth of parameter fluctutations in molecular evolution. In this study, we compare patterns of codon usage and protein evolution among five species in the D. melanogaster subgroup (D. melanogaster, simulans, sechellia, yakuba, and erecta) for close to 10,000 genes. We employ a maximum likelihood approach to infer ancestral states and assign substitutions to five lineages. The magnitude of parameters governing “silent” DNA evolution appears to have varied frequently among lineages, genomic regions, and synonymous families. At least some of this heterogeneity is consistent with lineage-specific selection intensity. Large-scale changes in expression patterns may underly strong regional heterogeneity in codon bias evolution.

References: (1) Akashi, H., W.Y. Ko, S. Piao, A. John, P. Goel, C. F. Lin, and A. Vitins, 2006 Molecular evolution in the Drosophila melanogaster species subgroup: Frequent parameter fluctuations on the time-scale of molecular divergence. Genetics 172: 1711-1726. (2) Ko, W. Y., S. Piao, and H. Akashi, 2006 Strong regional heterogeneity in base composition evolution on the Drosophila X chromosome. Genetics 174: 349-362.

04/04/07

Speaker: Dr. Saby Das- Department of Biology

Title: "Signatures of Dynamic Evolution on Immunoglobulin Variable Gene Families."

Abstract: The distinction of light chain variable genes (V_L) as kappa (V ) and lambda (V ) are often confusing and their evolutionary history is unclear. Different methods for tree building can be used but none of them so far resolved the confusion. On the other hand, the frequency of expansion and contraction of various heavy chain variable (V_H) gene families and their importance for the evolution of immunoglobulin heavy chain repertoire in vertebrates is an open question. To understand the evolutionary dynamics of V_L and V_H genes we identified V_L and V_H sequences from several completely sequenced vertebrate genomes. We clearly defined and distinguished the kappa and lambda variable genes on the basis of three distinct but conserved features. We proposed the kappa ancient hypothesis and a model for the evolution of light chain variable genes. The ratio of the total number of kappa and lambda chain genes varied in different lineage. It is probably due to the differences in lineage specific expansion and/or contraction of V or V genes. The all vertebrate V_H genes can be phylogenetically separated into eight major groups (Group A – H), in which tetrapods are represented by three groups (groups F, G and H). There is a biased expansion of group H genes and/or group G genes. We hypothesized that this biased expansion can be correlated with the biased usage of group H genes and/or group G genes and this relationship is well conserved during evolution. There are enormous diversities in V_H gene numbers and gene orders in eutherian mammals, but the V_H locus is conserved in the subtelomeric region of the chromosome. This diversity in number and organization of V_H genes partly can be explained by differences in evolutionary turnover of subtelomeric regions in different species. Both V_H and V_L genes evolution can be characterized by birth-and-death model. There is a significant positive correlation between total numbers of V_H and V_L families as well as between the numbers of functional genes for the same. It supports the coevolution of V_H and V_L gene families in the peculiarities of the immune systems in various organisms.

References: (1) Hsu E, Pulham N et al (2006). “The plasticity of immunoglobulin gene systems in evolution.” Immunol Rev 210: 8-26.
(2) Zahorsky-Reeves JL, Gregory C (2006). “Similarities in the immunoglobulin response and VH gene usage in rhesus monkeys and humans exposed to porcine hepatocytes.” BMC Immunol. 7: 3. (3) Pilstrom L (2002). “ The mysterious immunoglobulin light chain.” Dev Comp Immunol 26: 207-215. (4) Sitnikova T, Su C (1998). “Coevolution of immunoglobulin heavy- and light chain variable region gene families” Mol Biol Evol 15: 617-625. (5) Ota T, Nei M (1994). “ Divergent evolution and evolution by the birth-and-death process in the immunoglobulin V_Hgene family” Mol Biol Evol 11: 469-482.

04/11/07

Speaker: Valer Gotea- Department of Biology

Title: "The protein coding potential of Alu elements."

Abstract: Transposable elements represent a significant portion of mammalian genomes, and have been shown to impact their functionality in several ways (Makalowski, 2000). Of particular interest to us is their contribution to proteomes, and we recently described cases of functional proteins that contain TE-encoded fragments (Gotea and Makalowski, 2006). Alu elements are particularly important to primate evolution, as they are very abundant (~1.2 million copies in the human genome, ~10% of the genome size) and contribute with alternatively spliced exons to many genes (Sorek et al, 2002). Here we investigate the potential of Alu elements to encode functional protein fragments. We also take advantage of the recently sequenced macaque genome to infer the selection acting on Aluternative exons, and we discuss controversial functional evidence supporting the existence of Aluternative gene variants (Shi et al., 1999).

References: (1) Gotea, V., W. Makalowski (2006) Do transposable elements really contribute to proteomes? Trends in Genetics 22(5): 260-267 (2) Makalowski, W. (2000) Genomic scrap yard: how genomes utilize all that junk. Gene 259(1-2): 61-67 (3) Shi, B. et al. (1999) Identification and characterization of Baxe, a novel Bax variant missing the BH2 and the transmembrane domains. Biochemical and Biophysical Research Communications 254: 779-785 (4) Sorek, R., G. Ast, D. Graur (2002) Alu-containing exons are alternatively spliced. Genoem Research 12: 1060-1067

04/18/07

Speaker: Song Li- Department of Biology

Title: "Global Regulation of Gene Expression in Guard Cells."

Abstract: Guard cells (GC) have been long studied for elucidation of ABA signal transduction using electrophysiological, biochemical and molecular genetic methods. Here we take a genomics approach to study the transcriptome of GC. We have established methods to obtain pure GC RNA with or without ABA treatment and have used these samples to hybridize whole genome Affymetrix chips (ATH1). Leaf (LF) RNA samples with or without ABA were also used to hybridize to ATH1 chips in parallel.

Gene expression in higher eukaryotes is a complex process and is under integrated control of both developmental and environmental cues. We study developmental control by looking at tissue specific gene expression profiles of Arabidopsis guard cells (GC) versus leaves (LF), and we study environmental control by comparing gene expression in the two tissues in response to the stress hormone, abscisic acid (ABA).

We use the gene expression profiles generated from our lab, and integrate other publicly available computational and experimental resources, to study four putative regulatory mechanisms that are likely to be involved in transcriptional regulation in GC and LF. The four mechanisms we look at are cis-regulatory element regulated gene expression, co-expression clusters on chromosomes, microRNA regulated gene expression and cis-antisense regulated gene expression. We finally evaluate the relative importance of four regulatory mechanisms using a log likelihood score (LLS).

References: Sona Pandey*, Song Li*, Zhixin Zhao*, Laetitia Perfus*, Liza Wilson*, Timothy Gookin*, and Sarah M. Assmann*

*Biology Department, Penn State University.

This reference not yet published.

04/25/07

Speaker: Jill Duarte- Department of Biology

Title: "Identification of conserved single copy nuclear genes in Arabidopsis, Populus, and rice and their phylogenetic utility."

Authors: Duarte, J. M., Wall, P. K., Beckmann, K., Landherr, L. L., Leebens-Mack, J. H., dePamphilis, C. W.

Abstract: Although the overwhelming majority of genes found in angiosperms are members of gene families, we have identified a series of genes that are conserved as single copy genes in the Arabidopsis, Populus, and rice genomes. To characterize these genes, we have performed a number of analyses examining GO annotations, cDNA length, number of exons, expression patterns, and presence in the Selaginella and Physcomitrella genomes. There are 1574 single copy nuclear genes conserved in Arabidopsis and rice; 727 single copy genes conserved in Arabidopsis, Populus, and rice; and the majority of these genes are also present in the Selaginella and Physcomitrella draft genomes. The selective forces leading to continuous loss of duplicated genes for some kinds of genes and not others are still unknown, but the collection of genes is biased toward organellar genes and genes of unknown biological function. Public EST sets for 41 species suggest that most of these genes are conserved as single or very low copy genes, though exceptions are seen especially in very recent polyploidy taxa. In order to explore the phylogenetic utility of a number of these genes we have performed a series of phylogenetic analyses using publicly available ESTs. Conserved single copy nuclear genes provide a vast source of new evidence for plant phylogeny, genome mapping, and other applications.

References:

Mort, M.-E., and D. J. Crawford. 2004. The continuing search: low-copy nuclear sequences for lower-level plant molecular phylogenetic studies. Taxon 53:257-261.

Sang, T. 2002. Utility of low-copy nuclear gene sequences in plant phylogenetics. Critical Reviews in Biochemistry and Molecular Biology 37:121-147.

Small, R. L., R. C. Cronn, and J. F. Wendel. 2004. Use of nuclear genes for phylogeny reconstruction in plants. Australian Systematic Botany 17:145-170.

05/02/07

Speaker: Dimitra Chalkia- Department of Biology

Title: “Phylogenetic Analysis of Formin Genes in Eukaryotes and Inference of their Functional Divergence.”

Abstract: One of the most interesting properties of the eukaryotic cell is the ability to change its shape and activity rapidly in response to internal and external signals. This property comes from the cell’s ability to remodel the actin and microtubule cytoskeletons with appropriate timing and precision. Recently, formin has emerged as a key molecular regulator of the eukaryotic cytoskeletal assembly and organization. Formin is a large multidomain protein that is expressed widely in mammalian cells. This dynamic molecule associates with a variety of other cellular factors and assembles actin filaments through a novel migratory mechanism. In this study we have shown that formin genes exist in all eukaryotic genomes while bacterial and archaeal genomes are devoid of formin or formin-like genes. Our phylogenetic analysis, based on formin’s most conserved module (FH2 module), suggests that multiple events of expansion and contraction of copy number have occurred in this gene family. Of special interest is the birth of all metazoan formin gene groups before the emergence of multicellular organisms. Unicellular organisms that form colonies under certain conditions (e.g., Monosiga brevicollis and Dictyostellium discoideum) have multiple copies of formin genes, which are orthologous to most animal formin genes. The pattern of modular architecture of eukaryotic formin proteins can be classified according to the phylogenetic clustering. The conservation of the functionally important residues in all formins implies that the core function of the FH2 domain, i.e. polymerization and assembly of actin filaments is conserved. Our data suggest that the high degree of divergence of different groups of formin molecules is a product of mutations that evolved in a more or less neutral fashion. We speculate that neutral mutations coupled with the insertion/deletion of specific modules provided the means for temporal and/or spatial differentiation of gene function and thus led to the evolution of a highly coordinated cytoskeletal regulatory system.

References: Higgs HN (2005) Formin proteins: a domain based approach. Trends Biochem. Sci. 30(6):342-353.Goode BL and Eck MJ (2007) Mechanism and function of formins in the control of actin assembly. Ann. Rev. Biochem 76:32.1-32.35.