Friday, December 09, 2005

Collected links to scientific discussions on genetics

Links to Notes on Genetics:
General Format for List:
......# Document
Academics Review

Cold Spring Harbor Laboratory
National Center for Biotechnology Information
......# Virtual Library on Genetics
......# Chales M Rader's Website. A Report on Genetically Engineered Crops
Two sections in the essay are relevant to the question of just how unnatural GMO crops are. These are the sections entitled It's Unlike Anything in Nature and Where Transgenes Go .
GMO Pundit
......# Natural GMOs Part 5. Jumping genes cause mutations
......# Natural GMOs Part 7. Nanobot Genetic Engineers called Helitrons created food crops we have used for thousands of years
......# Natural GMOs Part 8. Helitrons upclose, unplugged and sweaty.
......# Natural GMOs Part 9. Different flowering plants often add their genes to create new species.
......# Natural GMOs Part 11. Genetic Chaos on in nature.
......# Natural GMOs Part 12. Nanobot mules from rice to millet.
......# Examples of Nina Fedoroff's science relating to mobile DNA and plant genetics.
......# Gene Shuffling Techniques Lead to Practical Advances
......# More on Mobile DNA in Plants.
......# Jumping Genes Cause Dog Mutation.
......# What is JIGMOD? (Includes some discussion of natural transgenic events and DNA transfer).
......# Natural GMOs Part 14. Surprise in the Transib-erian Express.
......# Genetic dissection of particular genes and molecules versus whole organism biology.
......# Genetic dissection (reductionism) part 2.
......# Natural GMOs Part 16. nDart mobile DNA in rice.
......# Direct evidence of phenotypic diversity in conventional food crops.
......# Plant breeding and climate change.
......# Molecular markers and Soy oil fatty acid profiles.
......# Genetics of pathogen detection by Leucine rich repeat proteins in animals insects and plants.
......# The Full Monty on gene evolution.
......# Natural GMOs Part 19. The Evolutionary Arms Race.
......# Natural GMOs Part 20. The Red Queen.
......# How mutants help us understand normal plant life activities.
......# Natural GMOs Part 21. DNA Gymnastics separates humans from chimpanzees.
......# Natural GMOs Part 22. Search for New Mysteries.
......# Natural GMOs Part 23. Power of Parasites.
Maize Genetics
......# The MaizeGDB website
USDA Agricultural Research Service comments:

Maize genetics and genomics database available on website
December 15, 2005
Luis Pons

Need some detailed data on the genetics and genomics of maize? Then the Agricultural Research Service (ARS) and Iowa State University (ISU) have just the website for you.
The Maize Genetics and Genomics Database, also known as the MaizeGDB, offers loads of information on the traits, genetic sequences and other related features of maize (Zea mays L. ssp. mays), including those aspects having to do with breeding and crop improvement.
The site is a portal to cutting-edge research on this staple crop, as well as to landmark work done decades ago. It also provides contact information for more than 2,400 cooperative researchers, along with web-based tools for ordering items such as maize stocks and cloned sequences.
MaizeGDB was developed by geneticist Carolyn Lawrence and information technology specialists Trent Seigfried and Darwin Campbell at ARS' Corn Insects and Crop Genetics Research Unit in Ames, Iowa, in collaboration with ISU researcher Volker Brendel in Ames and geneticist Mary Schaeffer of ARS' Plant Genetics Research Unit in Columbia, Mo.
According to Lawrence, the site presents maize information in a way that clearly summarizes biological relationships, and features easy-to-use computational tools. With it, a researcher can connect how a plant looks to the genetic sequences responsible for causing its phenotype.
Lawrence explained that maize is much more than a source of food for both people and livestock worldwide. It's also used in the manufacture of diverse commodities including glue, paint, insecticides, toothpaste, rubber tires, rayon and molded plastics. It is also the nation's major source of ethanol.
MaizeGDB is the successor to, and encapsulates the data from, two pioneer databases devoted to maize research: the Maize Database (MaizeDB), started by former ARS geneticist Ed Coe in 1991, and ZmDB, which was launched by the National Science Foundation-funded Maize Gene Discovery Project (MGDP).

ARS is the U.S. Department of Agriculture's chief in-house scientific research agency.

......# Maize Genetics Conferences

......# Nina Fedoroff on Maize genetics
......# GMO Pundit on why hybrids offer advantages to the farmer

......# Walbot Maize Lab Stanford University
......# Walbot Lab Web Links

Mobile genes, transposons

......# Explanation of jumping genes and variegated corn.
......# Kimball on Mobile DNA
Dr. Margaret G. Kidwell, Regents Professor
The University of Arizona

Positions and Education
Regents' Professor, Ecology & Evolutionary Biology, University of Arizona 1994-present

Honors and Awards
Elected Member, National Academy of Sciences, 1996
Regents' Professor of Ecology & Evolutionary Biology, 1994
Wilhelmina Key Invited Lecturer, American Genetic Association, 1993
Elected Fellow, American Academy of Arts and Sciences, 1993
Elected Fellow, American Association for the Advancement of Science, 1992

Research Interests
Margaret Kidwell studies the population genetics and evolution of transposable elements in Drosophila and other Diptera. Recent and ongoing projects include examination of the frequency and possible mechanisms of horizontal transfer of mobile elements and the reconstruction of phylogenetic trees based on molecular data. She also uses computer simulations to model the dynamics of transposable elements in insect populations and population cage studies to explore the feasibility of using transposable elements as genetic drivers in Drosophila and mosquito populations. Other projects include the population genetics of malaria epidemiology and the mechanisms controlling immune responses to infection in Anopheline mosquitoes.
Selected Publications

1. Kidwell, M. G. and D. R. Lisch. 2001. Perspective: Transposable elements, parasitic DNA and genome evolution. Evolution 55: 1-24.

2. Kidwell, M. G. and D. R. Lisch. 2001. Transposable Elements as Sources of Genomic Variation. Chapter In Mobile DNA II. American Society of Microbiology Press. In press.

3. Lyozin, G. T., Makarova, K. S., Velikodvorskaja, V. V., Zelentsova, H. S., Khechumian, R. R., Kidwell, M. G., Koonin, E. V., and M. B. Evgen'ev. 2001. The structure and evolution of Penelope in the Drosophila virilis species group: an ancient lineage of retroelements. J. Mol. Evol. In press.

4. Kidwell, M. G. and D. R. Lisch. 2000. Transposable elements and host genome evolution. Trends Ecol. Evol. 15: 95-99.

5. Kidwell, M. G. and M. B. Evgen'ev. 2000. How valuable are model organisms for transposable element studies? Genetica 107:103-111

6. Evgen'ev, M. B., Zelentsova, H., Mnjoian, L., Poluectova,H., and M. G. Kidwell 2000. Invasion of Drosophila virilis by the Penelope transposable element. Chromosoma 109:350-357.

7. Silva, J. C. and M. G. Kidwell. 2000. Selection and horizontal transfer in the evolution of P elements. Mol. Biol. Evol. 17:1542-1557

8. Evgen'ev, M. B., Zelentsova, H., Poluectova, H., Lyozin, G. T., Veleikodvorskaja, V., Pyatkov, K. I., Zhivotovsky, L. A. and Kidwell, M. G. 2000. Mobile elements and chromosomal evolution in the virilis group of Drosophila. Proc. Natl. Acad. Sci. USA 97:11337-11342.

9. Lee, S. H., Clark, J. B., and M. G. Kidwell. 1999. A P-homologous sequence in the house fly, Musca domestica. Insect Molecular Biology 8:491-500.

10. Zelentsova, H., Poluectova, H., Mnjoian, L., G. Lyozin, V. Veleikodvorskaja, L. Zhivotovski, M. G. Kidwell, and M. B. Evgen'ev. 1999. Distribution and evolution of mobile elements in the virilis species group of Drosophila. Chromosoma 108: 443-456.

11. Kidwell, M. G. 1997. Hybrid dysgenesis determinants and other useful transposable elements. In Drosophila. Encyclopedia of Genetics. E. C. R. Reeve (ed.). Dearborn Publishers. New York.

Older Publications

1. Kidwell, M. G., J. F. Kidwell & J. A. Syed 1977. Hybrid dysgenesis in D. melanogaster: a syndrome of aberrant traits including mutation, sterility & male recombination. Genetics 36: 813-33.

2. Bingham, P. M., M. G. Kidwell & G. M. Rubin 1982. The molecular basis of P-M hybrid dysgenesis: The role of the P element, a P strain-specific transposon family. Cell 29: 995-1004.

3. Kidwell, M. G. 1983. Evolution of hybrid dysgenesis determinants in Drosophila melanogaster. Proc. Nat. Acad. Sci. USA 80: 1655-1659.

4. Anxolabéhère, D., M. G. Kidwell & G. Periquet 1988. Molecular characteristics of diverse populations are consistent with the hypothesis of a recent invasion of Drosophila melanogaster by mobile P elements. Mol. Biol. Evol. 5: 252-269.

5. Daniels, S. B., K. R. Peterson, L. D. Strausbaugh, M. G. Kidwell & A. Chovnick 1990. Evidence for horizontal transmission of the P transposable element between Drosophila species. Genetics 124: 339-355.

6. Houck, M. A., J. B. Clark, K. R. Peterson & M. G. Kidwell 1991. Possible horizontal transfer of Drosophila genes by the mite Proctolaelaps regalis. Science 253: 1125-1129.

7. Kidwell, M. G. 1993. Lateral transfer in natural populations of eukaryotes. Ann. Rev. Genet. 27: 235-256.

8. Clark, J. B., W. P. Maddison & M. G. Kidwell 1994. Phylogenetic analysis supports horizontal transfer of P transposable elements. Mol. Biol. Evol. 11:40-50.

9. Kidwell, M. G. and D. Lisch. 1997. Transposable elements as sources of variation in animals and plants. Proc. Natl. Acad. Sci. 94: 7704-7711.

10. Clark, J. B. and M. G. Kidwell 1997. A phylogenetic perspective on P element evolution in Drosophila. Proc. Natl. Acad. Sci. USA 94: 11428-11433.
......# Jumping genes in the dog
......# Nina Fedoroff
......# See also numerous other Natural GMOs posts listed under GMO Pundit above.
......# Uncle Osmar and his friend Stowaway in the rice genome.
......# Throwing nDarts.
......# Margaret Kidwell's 2000 review, and RAG genes too.
Treasures in the attic: Rolling circle transposons discovered in eukaryotic genomes
Cédric Feschotte and Susan R. Wessler

Since the advent of methodologies to analyze the content of whole genomes (e.g., renaturation kinetics and Cot analysis), it has been known that a large fraction of eukaryotic genomes is highly repetitive.Recent computer-assisted analysis of several sequenced eukaryotic genomes, including Caenorhabditis elegans, Drosophila melanogaster, Arabidopsis thaliana, and humans, has demonstrated that most repetitive DNA is composed of or derived from transposable elements (TEs). In the human genome, for example, TEs are the single most abundant component, accounting for over 40% of the total DNA. Although this amount of TEs is viewed as a hindrance to those engaged in the determination and assembly of DNA sequence, the availability of both complete and partial eukaryotic genome sequences is providing TE biologists with a bonanza of raw material that is being used to understand how genomes evolve.

Before the report in PNAS by Kapitonov and Jurka, all eukaryotic TEs were thought to use one of two mechanisms for transposition. Class 1, or retrotransposons, transpose via an RNA intermediate in reactions catalyzed by element-encoded proteins, including reverse transcriptase. In contrast, the transposon itself is the intermediate for class 2 elements where an element-encoded transposase catalyzes reactions, resulting in TE excision from one site and reinsertion elsewhere in the genome (the so-called cut-and-paste mechanism). In addition to these two mechanisms, some prokaryotic TEs (called IS or insertion sequences), move by another mechanism called rolling circle (RC) transposition. This process is similar to the RC replication of some plasmids, single-stranded (ss) bacteriophage, and plant geminiviruses. In a recent issue of PNAS, Kapitonov and Jurka report that RC transposons also occur in eukaryotes where, surprisingly, they comprise about 2% of the genomes of A. thaliana and C. elegans.

PNAS July 31, 2001 vol. 98 no. 16 8923-8924
Genome Research
Doubling genome size without polyploidization: Dynamics of retrotransposition-driven genomic expansions in Oryza australiensis, a wild relative of rice
Benoit Piegu1, Romain Guyot1, Nathalie Picault1, Anne Roulin1, Abhijit Saniyal3, Hyeran Kim4, Kristi Collura4, Darshan S. Brar2, Scott Jackson3, Rod A. Wing4 and Olivier Panaud1,1
Genome Research 16:1262-1269, 2006

1Laboratoire Génome et Développement des Plantes, UMR 5096 CNRS-IRD, Université de Perpignan, Perpignan 66860, France; , 2Plant Breeding Genetics and Biochemistry Division, International Rice Research Institute, Manila 1099, Philippines, USA; , 3Agricultural Genomics, Purdue University, West Lafayette, Indiana 47907, USA; , 4Arizona Genomics Institute, Department of Plant Sciences, University of Arizona, Tucson, Arizona 85721, USA

Retrotransposons are the main components of eukaryotic genomes, representing up to 80% of some large plant genomes. These mobile elements transpose via a "copy and paste" mechanism, thus increasing their copy number while active. Their accumulation is now accepted as the main factor of genome size increase in higher eukaryotes, besides polyploidy. However, the dynamics of this process are poorly understood. In this study, we show that Oryza australiensis, a wild relative of the Asian cultivated rice O. sativa, has undergone recent bursts of three LTR-retrotransposon families. This genome has accumulated more than 90,000 retrotransposon copies during the last three million years, leading to a rapid twofold increase of its size. In addition, phenetic analyses of these retrotransposons clearly confirm that the genomic bursts occurred posterior to the radiation of the species. This provides direct evidence of retrotransposon-mediated variation of genome size within a plant genus.

Nature Magazine.
......# Human Genome Collection
It is now more than 15 years since work began sequencing the 2.85 billion nucleotides of the human genome. While the draft sequence was published in Nature in 2001, researchers at the Human Genome Project continued to fill the gaps and subject individual chromosomes to ever more detailed analyses. Nature is proud to present here the complete and comprehensive DNA sequence of the human genome as a freely available resource. Produced with support from our sponsors. Nature carries sole responsibility for all editorial content.
.......# Role of mobile genes in evolution

5 October 2006 Nature
Volume 443 Number 7111 p521
Editor's Summary
Jump to it

Once dismissed as junk, selfish or parasitic DNA, transposable elements or 'jumping genes' are now regarded as major players in many of the processes that reshape the genome and control the activity of its genes. Christian Biémont and Cristina Vieira consider the two-pronged evolutionary impact of transposable elements as promoters of genetic diversity, and as agents for inflicting genetic damage and causing disease.

News and Views Feature: Genetics: Junk DNA as an evolutionary force, p521

Transposable elements were long dismissed as useless, but they are emerging as major players in evolution. Their interactions with the genome and the environment affect how genes are translated into physical traits.

Christian Biémont and Cristina Vieira

Cite the following:

1: Gene. 2005 Jan 17;345(1):101-11. Epub 2004 Dec 25.

Transposable elements as a source of genetic innovation: expression and evolution of a family of retrotransposon-derived neogenes in mammals.

Brandt J, Schrauth S, Veith AM, Froschauer A, Haneke T, Schultheis C, Gessler M, Leimeister C, Volff JN.

Biofuture Research Group, Physiologische Chemie I, Biozentrum, University of Wurzburg, am Hubland, D-97074 Wurzburg, Germany.

A family of functional neogenes called Mart, related to the gag gene of Sushi-like long terminal repeat retrotransposons from fish and amphibians, is present in the genome of human (11 genes) and other primates, as well as in mouse (11 genes), rat, dog (12 genes), cat, and cow. Mart genes have lost their capacity of retrotransposition through non-functionalizing rearrangements having principally affected long terminal repeats and pol open reading frame. Most Mart genes are located on the X chromosome in different mammals. Sequence database analysis suggested that Mart genes are present in opossum (marsupial), but absent from the genome of chicken. Hence, the Mart gene family might have been formed from Sushi-like retrotransposon(s) after the split of birds and mammals (310 myr ago), but before the divergence between placental mammals and marsupials (170 myr ago). RT-PCR analysis showed that at least six Mart genes are expressed during mouse embryonic development, with in situ hybridization analysis revealing rather ubiquitous expression patterns. Mart expression was
also detected in adult mice, with some genes being expressed in all tissues tested, while others showed a much more restricted expression pattern. Although additional analysis will be required to establish the function of the retrotransposon-derived Mart neogenes, these observations support the evolutionary importance of retrotransposable elements as a source of genetic novelty.

PMID: 15716091 [PubMed - indexed for MEDLINE]

2: Cytogenet Genome Res. 2005;110(1-4):342-52.

Impact of transposable elements on the evolution of mammalian gene regulation.

Medstrand P, van de Lagemaat LN, Dunn CA, Landry JR, Svenback D, Mager DL.

Department of Cell and Molecular Biology, Biomedical Centre, Lund University, Lund, Sweden.

Transposable elements (TEs) are present in all organisms and nearly half of the human and mouse genome is derived from ancient transpositions. This fact alone suggests that TEs have played a major role in genome organization and evolution.
Studies undertaken over the last two decades or so clearly show that TEs of various kinds have played an important role in organism evolution. Here we review the impact TEs have on the evolution of gene regulation and gene function with an emphasis on humans. Understanding the mechanisms resulting in genomic change is central to our understanding of gene regulation, genetic disease and genome evolution. Full comprehension of these biological processes is not possible without an in depth knowledge of how TEs impact upon the genome.

Publication Types:

PMID: 16093686 [PubMed - indexed for MEDLINE]

3: Curr Opin Plant Biol. 2006 Apr;9(2):157-63. Epub 2006 Feb 3.

Organization and variability of the maize genome.

Messing J, Dooner HK.

Waksman Institute of Microbiology, Rutgers, The State University of New Jersey, 190 Frelinghuysen Road, Piscataway, New Jersey 08854, USA.

With a size approximating that of the human genome, the maize genome is about to become the largest plant genome yet sequenced. Contributing to that size are a whole-genome duplication event and a retrotransposition explosion that produced
a large amount of repetitive DNA. This DNA is greatly under-represented in cDNA collections, so analysis of the maize transcriptome has been an expedient way of assessing the gene content of maize. Over 2 million maize cDNA sequences are now available, making maize the third most widely studied organism, behind mouse and man. To date, the sequencing of large-sized DNA clones has been largely driven by the genetic interests of different investigators. The recent construction of
a physical map that is anchored to the genetic map will aid immensely in the maize genome-sequencing effort. However, studies showing that the repetitive DNA component is highly polymorphic among maize inbred lines point to the need to
sample vertically a few specific regions of the genome to evaluate the extent and importance of this variability.

Publication Types:

PMID: 16459130 [PubMed - indexed for MEDLINE]

4: Genome Res. 2006 Jul;16(7):864-74. Epub 2006 May 22.

Functional noncoding sequences derived from SINEs in the mammalian genome.

Nishihara H, Smit AF, Okada N.

Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.

Recent comparative analyses of mammalian sequences have revealed that a large number of nonprotein-coding genomic regions are under strong selective constraint. Here, we report that some of these loci have been derived from a newly defined family of ancient SINEs (short interspersed repetitive elements).
This is a surprising result, as SINEs and other transposable elements are commonly thought to be genomic parasites. We named the ancient SINE family AmnSINE1, for Amniota SINE1, because we found it to be present in mammals as well as in birds, and some copies predate the mammalian-bird split 310 million years ago (Mya). AmnSINE1 has a chimeric structure of a 5S rRNA and a tRNA-derived SINE, and is related to five tRNA-derived SINE families that we characterized here in the coelacanth, dogfish shark, hagfish, and amphioxus genomes. All of the newly described SINE families have a common central domain that is also shared by zebrafish SINE3, and we collectively name them the DeuSINE (Deuterostomia SINE) superfamily. Notably, of the approximately 1000 still identifiable copies of AmnSINE1 in the human genome, 105 correspond to loci phylogenetically highly conserved among mammalian orthologs. The conservation is strongest over the central domain. Thus, AmnSINE1 appears to be the best example of a transposable element of which a significant fraction of
the copies have acquired genomic functionality.

PMID: 16717141 [PubMed - indexed for MEDLINE]

5: Dev Cell. 2004 Oct;7(4):597-606.

Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos.

Peaston AE, Evsikov AV, Graber JH, de Vries WN, Holbrook AE, Solter D, Knowles BB.

The Jackson Laboratory, Bar Harbor, ME 04609, USA.

A comprehensive analysis of transposable element (TE) expression in mammalian full-grown oocytes reveals that LTR class III retrotransposons make an unexpectedly high contribution to the maternal mRNA pool, which persists in cleavage stage embryos. The most abundant transcripts in the mouse oocyte are from the mouse transcript (MT) retrotransposon family, and expression of this and other TE families is developmentally regulated. Furthermore, TEs act as alternative promoters and first exons for a subset of host genes, regulating their expression in full-grown oocytes and cleavage stage embryos. To our
knowledge, this is the first example of TEs initiating synchronous, developmentally regulated expression of multiple genes in mammals. We propose that differential TE expression triggers sequential reprogramming of the embryonic genome during the oocyte to embryo transition and in preimplantation embryos.

PMID: 15469847 [PubMed - indexed for MEDLINE]

6: Cytogenet Genome Res. 2006;113(1-4):109-15.

Repetitive elements in imprinted genes.

Walter J, Hutter B, Khare T, Paulsen M.

Genetik/Epigenetik, FR 8.3 Biowissenschaften, Universitat des Saarlandes, Saarbrucken, Germany.

Genomic imprinting in mammals results in mono-allelic expression of about 80 genes depending on the parental origin of the alleles. Though the epigenetic mechanisms underlying imprinting are rather clear, little is known about the genetic basis for these epigenetic mechanisms. It is still rather enigmatic which sequence features discriminate imprinted from non-imprinted genes/regions and why and how certain sequence elements are recognized and differentially marked in the germlines. It seems likely that specific DNA elements serve as signatures that guide the necessary epigenetic modification machineries to the imprinted regions. Inter- and intraspecific comparative genomic studies suggest that the unusual occurrence and distribution of various types of repetitive elements within imprinted regions may represent such genomic imprinting
signatures. In this review we summarize the various observations made and discuss them in light of experimental data. 2006 S. Karger AG, Basel.

Publication Types:

PMID: 16575169 [PubMed - indexed for MEDLINE]

7: Nucleic Acids Res. 2005 Apr 7;33(6):2052-9. Print 2005.

Argonaute protein PIWI controls mobilization of retrotransposons in the Drosophila male germline.

Kalmykova AI, Klenov MS, Gvozdev VA.

Institute of Molecular Genetics RAS Kurchatov square 2, 123 182 Moscow, Russia.

Proteins of the Argonaute family have been identified as key components of RNA interference (RNAi) pathway. RNAi-related mechanisms are implicated in the regulation of gene expression and repression of transposable elements in
eukaryotes. The piwi gene encoding protein of the Drosophila Argonaute family was shown to be required for the germ stem cells maintenance. Here, we show that piwi is involved in silencing of LTR retrotransposons in testes. piwi mutations led to derepression of endogenous retrotransposon copia as well as to upregulation of the reporter gene driven by copia LTR. piwi mutation causes accumulation of retrotransposon mdg1 transcripts at the apical tip of testes, including germinal proliferative center where PIWI protein was shown to be expressed. We applied inverse PCR approach to detect the newly arisen insertions of the mdg1 retrotransposon in the progeny of individual piwi mutant males.
Owing to piwi mutation a high rate of mdg1 transpositions was revealed. Thus, piwi is involved in the silencing of retrotransposons in the precursors of male gametes. Our results provide the first evidence that protein of the Argonaute
family prevents retrotranspositions. It is supposed that the disturbance of RNA silencing system in germinal cells might cause transposition burst.

PMID: 15817569 [PubMed - indexed for MEDLINE]

8: Heredity. 2006 Feb;96(2):195-202.

RNAi: a defensive RNA-silencing against viruses and transposable elements.

Buchon N, Vaury C.

INSERM U384, 28 place Henri Dunant, 63000 Clermont-Ferrand, France.

RNA silencing is a form of nucleic-acid-based immunity, targeting viruses and genomic repeated sequences. First documented in plants and invertebrate animals, this host defence has recently been identified in mammals. RNAi is viewed as a conserved ancient mechanism protecting genomes from nucleic acid invaders.
However, these tamed sequences are known to occasionally escape this host surveillance and invade the genome of their host. This response is consistent with the overall idea that parasitic sequences compete with cells to systematically counter host defences. Using examples taken from the current literature, we illustrate the dynamic move-countermove game played between these two protagonists, the host cell and its parasitic sequences, and discuss the consequences of this game on genome stability.

Publication Types:

PMID: 16369574 [PubMed - indexed for MEDLINE]

9: Nature. 2005 Jun 16;435(7044):903-10.

Comment in:
Nature. 2005 Jun 16;435(7044):890-1.

Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition.

Muotri AR, Chu VT, Marchetto MC, Deng W, Moran JV, Gage FH.

Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.

Revealing the mechanisms for neuronal somatic diversification remains a central challenge for understanding individual differences in brain organization and function. Here we show that an engineered human LINE-1 (for long interspersed
nuclear element-1; also known as L1) element can retrotranspose in neuronal precursors derived from rat hippocampus neural stem cells. The resulting retrotransposition events can alter the expression of neuronal genes, which, in turn, can influence neuronal cell fate in vitro. We further show that retrotransposition of a human L1 in transgenic mice results in neuronal somatic mosaicism. The molecular mechanism of action is probably mediated through Sox2, because a decrease in Sox2 expression during the early stages of neuronal differentiation is correlated with increases in both L1 transcription and
retrotransposition. Our data therefore indicate that neuronal genomes might not be static, but some might be mosaic because of de novo L1 retrotransposition events.

PMID: 15959507 [PubMed - indexed for MEDLINE]

10: Cytogenet Genome Res. 2005;110(1-4):242-9.

Host defenses to transposable elements and the evolution of genomic imprinting.

McDonald JF, Matzke MA, Matzke AJ.

Department of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA.

Genomic imprinting is the differential expression of maternally and paternally inherited alleles of specific genes. Several organismic level hypotheses have been offered to explain the evolution of genomic imprinting. We argue that evolutionary explanations of the origin of imprinting that focus exclusively on the organismic level are incomplete. We propose that the complex molecular mechanisms that underlie genomic imprinting originally evolved as an adaptive response to the mutagenic potential of transposable elements (TEs). We also present a model of how these mechanisms may have been co-opted by natural selection to evolve molecular features characteristic of genomic imprinting.

Publication Types:

PMID: 16093678 [PubMed - indexed for MEDLINE]

11: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9. Epub 2005 Jul 11.

Comment in:
Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10413-4.

Epigenetic differences arise during the lifetime of monozygotic twins.

Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller

Epigenetics Laboratory, Spanish National Cancer Centre (CNIO), Melchor Fernandez Almagro 3, 28029 Madrid, Spain.

Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to disease and a wide range of anthropomorphic features. There are several possible explanations for these observations, but one is the existence of epigenetic differences. To address this issue, we examined the global and locus-specific differences in DNA methylation and histone acetylation of a large cohort of monozygotic twins. We found that, although twins are epigenetically indistinguishable during the early years of life, older monozygous twins exhibited remarkable differences in their overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation, affecting their gene-expression portrait. These findings indicate
how an appreciation of epigenetics is missing from our understanding of how different phenotypes can be originated from the same genotype.

PMID: 16009939 [PubMed - indexed for MEDLINE]

12: Plant Cell. 2005 Dec;17(12):3301-10. Epub 2005 Oct 28.

Establishment of the vernalization-responsive, winter-annual habit in Arabidopsis requires a putative histone H3 methyl transferase.

Kim SY, He Y, Jacob Y, Noh YS, Michaels S, Amasino R.

Department of Biology, Indiana University, Bloomington, 47405, USA.

Winter-annual accessions of Arabidopsis thaliana are often characterized by a requirement for exposure to the cold of winter to initiate flowering in the spring. The block to flowering prior to cold exposure is due to high levels of the flowering repressor FLOWERING LOCUS C (FLC). Exposure to cold promotes flowering through a process known as vernalization that epigenetically represses FLC expression. Rapid-cycling accessions typically have low levels of FLC expression and therefore do not require vernalization. A screen for mutants in which a winter-annual Arabidopsis is converted to a rapid-cycling type has identified a putative histone H3 methyl transferase that is required for FLC expression. Lesions in this methyl transferase, EARLY FLOWERING IN SHORT DAYS (EFS), result in reduced levels of histone H3 Lys 4 trimethylation in FLC chromatin. EFS is also required for expression of other genes in the FLC clade, such as MADS AFFECTING FLOWERING2 and FLOWERING LOCUS M. The requirement for EFS to permit expression of several FLC clade genes accounts for the ability of efs lesions to suppress delayed flowering due to the presence of FRIGIDA, autonomous pathway mutations, or growth in noninductive photoperiods. efs mutants exhibit pleiotropic phenotypes, indicating that the role of EFS is not limited to the
regulation of flowering time.

PMID: 16258034 [PubMed - indexed for MEDLINE]

13: Nature. 2004 Jul 22;430(6998):471-6.

Role of transposable elements in heterochromatin and epigenetic control.

Lippman Z, Gendrel AV, Black M, Vaughn MW, Dedhia N, McCombie WR, Lavine K, Mittal V, May B, Kasschau KD, Carrington JC, Doerge RW, Colot V, Martienssen R.

Watson School of Biological Sciences and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.

Heterochromatin has been defined as deeply staining chromosomal material that remains condensed in interphase, whereas euchromatin undergoes de-condensation.
Heterochromatin is found near centromeres and telomeres, but interstitial sites of heterochromatin (knobs) are common in plant genomes and were first described in maize. These regions are repetitive and late-replicating. In Drosophila, heterochromatin influences gene expression, a heterochromatin phenomenon called position effect variegation. Similarities between position effect variegation in Drosophila and gene silencing in maize mediated by "controlling elements" (that
is, transposable elements) led in part to the proposal that heterochromatin is composed of transposable elements, and that such elements scattered throughout the genome might regulate development. Using microarray analysis, we show that
heterochromatin in Arabidopsis is determined by transposable elements and related tandem repeats, under the control of the chromatin remodelling ATPase DDM1 (Decrease in DNA Methylation 1). Small interfering RNAs (siRNAs) correspond
to these sequences, suggesting a role in guiding DDM1. We also show that transposable elements can regulate genes epigenetically, but only when inserted within or very close to them. This probably accounts for the regulation by DDM1
and the DNA methyltransferase MET1 of the euchromatic, imprinted gene FWA, as its promoter is provided by transposable-element-derived tandem repeats that are associated with siRNAs.

PMID: 15269773 [PubMed - indexed for MEDLINE]

14: Nutrition. 2004 Jan;20(1):63-8.

Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases.

Waterland RA, Jirtle RL.

Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Publication Types:

PMID: 14698016 [PubMed - indexed for MEDLINE]

15: Genetics. 2005 Nov;171(3):1183-94. Epub 2005 Sep 12.

Human endogenous retroviral elements as indicators of ectopic recombination events in the primate genome.

Hughes JF, Coffin JM.

Department of Molecular Microbiology and Program in Genetics, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

HERV elements make up a significant fraction of the human genome and, as interspersed repetitive elements, have the capacity to provide substrates for ectopic recombination and gene conversion events. To understand the extent to
which these events occur and gain further insight into the complex evolutionary history of these elements in our genome, we undertook a phylogenetic study of the long terminal repeat sequences of 15 HERV-K(HML-2) elements in various
primate species. This family of human endogenous retroviruses first entered the primate genome between 35 and 45 million years ago. Throughout primate evolution, these elements have undergone bursts of amplification. From this analysis, which is the largest-scale study of HERV sequence dynamics during primate evolution to date, we were able to detect intraelement gene conversion and recombination at five HERV-K loci. We also found evidence for replacement of an ancient element by another HERV-K provirus, apparently reflecting an occurrence of retroviral integration by homologous recombination. The high
frequency of these events casts doubt on the accuracy of integration time estimates based only on divergence between retroelement LTRs.

PMID: 16157677 [PubMed - indexed for MEDLINE]

16: Curr Opin Genet Dev. 1998 Jun;8(3):343-50.

Mobile elements and disease.

Kazazian HH Jr.

Department of Genetics, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104, USA.

A substantial fraction of mammalian genomes is composed of mobile elements and their remnants. Recent insertions of LTR-retrotransposons, non-LTR retrotransposons, and non-autonomous retrotransposons have caused disease frequently in mice, but infrequently in humans. Although many of these elements are defective, a number of mammalian non-LTR retrotransposons of the L1 type are capable of autonomous retrotransposition. The mechanism by which they
retrotranspose and in turn aide the retrotransposition of non-autonomous elements is being elucidated.

Publication Types:

PMID: 9690999 [PubMed - indexed for MEDLINE]

17: Mol Cell Biol. 2003 May;23(10):3566-74.

Direct involvement of HERV-W Env glycoprotein in human trophoblast cell fusion and differentiation.

Frendo JL, Olivier D, Cheynet V, Blond JL, Bouton O, Vidaud M, Rabreau M, Evain-Brion D, Mallet F.

Unite INSERM 427, Faculte des Sciences Pharmaceutiques et Biologiques, Universite Rene Descartes, 75006 Paris, France.

We recently demonstrated that the product of the HERV-W env gene, a retroviral envelope protein also dubbed syncytin, is a highly fusogenic membrane glycoprotein inducing the formation of syncytia on interaction with the type D mammalian retrovirus receptor. In addition, the detection of HERV-W Env protein (Env-W) expression in placental tissue sections led us to propose a role for this fusogenic glycoprotein in placenta formation. To evaluate this hypothesis, we analyzed the involvement of Env-W in the differentiation of primary cultures of human villous cytotrophoblasts that spontaneously differentiate by cell
fusion into syncytiotrophoblasts in vitro. First, we observed that HERV-W env mRNA and glycoprotein expression are colinear with primary cytotrophoblast differentiation and with expression of human chorionic gonadotropin (hCG), a marker of syncytiotrophoblast formation. Second, we observed that in vitro stimulation of trophoblast cell fusion and differentiation by cyclic AMP is also associated with a concomitant increase in HERV-W env and hCG mRNA and protein expression. Finally, by using specific antisense oligonucleotides, we demonstrated that inhibition of Env-W protein expression leads to a decrease of trophoblast fusion and differentiation, with the secretion of hCG in culture medium of antisense oligonucleotide-treated cells being decreased by fivefold.
Taken together, these results strongly support a direct role for Env-W in human trophoblast cell fusion and differentiation.

PMID: 12724415 [PubMed - indexed for MEDLINE]

18: Cytogenet Genome Res. 2005;110(1-4):25-34.

What transposable elements tell us about genome organization and evolution: the case of Drosophila.

Biemont C, Vieira C.

Laboratoire de Biometrie et Biologie Evolutive, UMR CNRS 5558, Universite Lyon
1, Villeurbanne, France.

Transposable elements (TEs) have been identified in every organism in which they have been looked for. The sequencing of large genomes, such as the human genome and those of Drosophila, Arabidopsis, Caenorhabditis, has also shown that they
are a major constituent of these genomes, accounting for 15% of the genome of Drosophila, 45% of the human genome, and more than 70% in some plants and amphibians. Compared with the 1% of genomic DNA dedicated to protein-coding
sequences in the human genome, this has prompted various researchers to suggest that the TEs and the other repetitive sequences that constitute the so-called "noncoding DNA", are where the most stimulating discoveries will be made in the
future (Bromham, 2002). We are therefore getting further and further from the original idea that this DNA was simply "junk DNA", that owed its presence in the genome entirely to its capacity for selfish transposition. Our understanding of
the structures of TEs, their distribution along the genomes, their sequence and insertion polymorphisms within genomes, and within and between populations and species, their impact on genes and on the regulatory mechanisms of genetic
expression, their effects on exon shuffling and other phenomena that reshape the genome, and their impact on genome size has increased dramatically in recent years. This leads to a more general picture of the impact of TEs on genomes,
though many copies are still mainly selfish or junk DNA. In this review we focus mainly on discoveries made in Drosophila, but we also use information about other genomes when this helps to elucidate the general processes involved in the organization, plasticity, and evolution of genomes.

Publication Types:

PMID: 16093655 [PubMed - indexed for MEDLINE]

19: Science. 2003 Nov 21;302(5649):1401-4.

Comment in:
Science. 2004 Apr 16;304(5669):389-90; author reply 389-90.
Science. 2004 Nov 5;306(5698):978; author reply 978.

The origins of genome complexity.

Lynch M, Conery JS.

Department of Biology, Indiana University, Bloomington, IN 47405, USA.

Complete genomic sequences from diverse phylogenetic lineages reveal notable increases in genome complexity from prokaryotes to multicellular eukaryotes. The changes include gradual increases in gene number, resulting from the retention
of duplicate genes, and more abrupt increases in the abundance of spliceosomal introns and mobile genetic elements. We argue that many of these modifications emerged passively in response to the long-term population-size reductions that
accompanied increases in organism size. According to this model, much of the restructuring of eukaryotic genomes was initiated by nonadaptive processes, and this in turn provided novel substrates for the secondary evolution of phenotypic
complexity by natural selection. The enormous long-term effective population sizes of prokaryotes may impose a substantial barrier to the evolution of complex genomes and morphologies.

PMID: 14631042 [PubMed - indexed for MEDLINE]

20: Evolution Int J Org Evolution. 2001 Jan;55(1):1-24.

Perspective: transposable elements, parasitic DNA, and genome evolution.

Kidwell MG, Lisch DR.

Department of Ecology and Evolutionary Biology, The University of Arizona,
Tucson 85721, USA.

The nature of the role played by mobile elements in host genome evolution is reassessed considering numerous recent developments in many areas of biology. It is argued that easy popular appellations such as "selfish DNA" and "junk DNA"
may be either inaccurate or misleading and that a more enlightened view of the transposable element-host relationship encompasses a continuum from extreme parasitism to mutualism. Transposable elements are potent, broad spectrum,
endogenous mutators that are subject to the influence of chance as well as selection at several levels of biological organization. Of particular interest are transposable element traits that early evolve neutrally at the host level
but at a later stage of evolution are co-opted for new host functions.

Publication Types:

PMID: 11263730 [PubMed - indexed for MEDLINE]

21: PLoS Genet. 2006 Mar;2(3):e36. Epub 2006 Mar 17.

Meiotically stable natural epialleles of Sadhu, a novel Arabidopsis retroposon.

Rangwala SH, Elumalai R, Vanier C, Ozkan H, Galbraith DW, Richards EJ.

Department of Biology, Washington University in St. Louis, St. Louis, Missouri,

Epigenetic variation is a potential source of genomic and phenotypic variation among different individuals in a population, and among different varieties within a species. We used a two-tiered approach to identify naturally occurring epigenetic alleles in the flowering plant Arabidopsis: a primary screen for transcript level polymorphisms among three strains (Col, Cvi, Ler), followed by a secondary screen for epigenetic alleles. Here, we describe the identification of stable, meiotically transmissible epigenetic alleles that correspond to one member of a previously uncharacterized non-LTR retroposon family, which we have
designated Sadhu. The pericentromeric At2g10410 element is highly expressed in strain Col, but silenced in Ler and 18 other strains surveyed. Transcription of this locus is inversely correlated with cytosine methylation and both the expression and DNA methylation states map in a Mendelian manner to stable cis-acting variation. The silent Ler allele can be converted by the epigenetic modifier mutation ddm1 to a meiotically stable expressing allele with an identical primary nucleotide sequence, demonstrating that the variation responsible for transcript level polymorphism among Arabidopsis strains is epigenetic. We extended our characterization of the Sadhu family members and show that different elements are subject to both genetic and epigenetic variation in natural populations. These findings support the view that an important component of natural variation in retroelements is epigenetic.

PMID: 16552445 [PubMed - indexed for MEDLINE]