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Schlötterer/Flatt: Population Genetics of epigenetic Programming in Drosophila

Epigenetic mechanisms cause heritable changes in gene expression independent of changes in DNA sequence. Histones, the protein components of chromatin, can be labeled with small chemical marks, and these epigenetic modifications in turn regulate chromatin structure and gene expression. The resulting changes can profoundly influence the phenotype, including medically and clinically relevant effects on cancer and tumorigenesis, telomere protection, metabolism, and aging. Remarkably, since epigenetic modifications can be passed on through cell divisions and over generations they represent a non-genetic hereditary system. Growing evidence suggests that heritable variation in phenotypic traits can be generated by epigenetic mechanisms even in the absence of genetic variation. These findings imply that epigenetic variation might generate phenotypic variation subject to natural selection, clearly posing a challenge to the traditional view that evolution by natural selection relies exclusively on variation engendered by random mutations in DNA. To date, however, epigenetic variation in natural populations and its evolutionary significance remains poorly understood. For the envisioned Vetmeduni Vienna career track postdoctoral project we propose to address three major unresolved questions in "evolutionary epigenetics" by using the powerful tools of population and functional genetics in the fruit fly (Drosophila melanogaster) model:

1. What is the extent and structure of epigenetic variation within and among populations? 
2. What is the hereditary stability of epigenetic modifications across generations and in different environments? 
3. Does epigenetic variation influence evolutionarily and ecologically relevant phenotypes?

Publication List

• Flatt T, Kawecki TJ (2004) Pleiotropic effects of methoprene-tolerant (Met), a gene involved in juvenile hormone metabolism, on life history traits in Drosophila melanogaster. Genetica 122, 141-160.
• Flatt T (2004) Assessing natural variation in genes affecting Drosophila lifespan. Mech Ageing Dev 125,155-159. [Invited Editorial].
• Flatt T (2005) The evolutionary genetics of canalization. Q Rev Biol 80, 287-316.
• Flatt T, Tu MP, Tatar M (2005) Hormonal pleiotropy and the juvenile hormone regulation of Drosophila development and life history. Bioessays 27, 999-1010. [Invited Review, With Cover Image].
• Flatt T, Moroz LL, Tatar M, Heyland A (2006) Comparing thyroid and insect hormone signaling. Integ Comp Biol 46, 777-794.
• Flatt T, Kawecki TJ (2007) Juvenile hormone as a regulator of the trade-off between reproduction and life span in Drosophila melanogaster. Evolution Int J Org Evolution 61, 1980-1991.
• Flatt T, Promislow DE (2007) Physiology. Still pondering an age-old question. Science 318, 1255-1256. [Invited Perspective].
• Flatt T, Min KJ, D'Alterio C, et al. (2008) Drosophila germ-line modulation of insulin signaling and lifespan. Proc Natl Acad Sci U S A 105, 6368-6373. [Featured in Partridge, L. 2008, Some highlights of research on aging with invertebrates, 2008, in Aging Cell, and in many specific and general interest news outlets].
• Flatt T, Heyland A, Rus F, Porpiglia E, Sherlock C, Yamamoto R, Garbuzov A, Palli SR, Tatar M, Silverman N (2008). Hormonal regulation of the humoral innate immune response in Drosophila melanogaster. J Exp Biol 211, 2712-2724. [Image Featured in JEB 2009 Calendar].
• Bauer JH, Morris SNS, Chang C, Flatt T, Wood JG, Helfand SL (2009). dSir2 and Dmp53 interact to mediate aspects of CR-dependent life span extension in D. melanogaster. Impact AGING 1, 38-48. [Featured in Donehower, L.A., 2009, Longevity regulation in flies: A role for p53, in Impact AGING].
• Catania F, Schlötterer C (2005) Non-African origin of a local beneficial mutation in D. melanogaster. Mol Biol Evol 22, 265-272.
• Schöfl G, Catania F, Nolte V, Schlötterer C (2005) African sequence variation accounts for most of the sequence polymorphism in non-African Drosophila melanogaster. Genetics 170, 1701-1709.
• Schäfer MA, Orsini L, McAllister BF, Schlötterer C (2006) Patterns of microsatellite variation through a transition zone of a chromosomal cline in Drosophila americana. Heredity 97, 291-295.
• Schlötterer C, Neumeier H, Sousa C, Nolte V (2006) Highly structured Asian Drosophila melanogaster populations: a new tool for hitchhiking mapping? Genetics 172, 287-292.
• Gibert JM, Peronnet F, Schlötterer C (2007) Phenotypic plasticity in Drosophila pigmentation caused by temperature sensitivity of a chromatin regulator network. PLoS Genet 3, e30.
• Wiehe T, Nolte V, Zivkovic D, Schlötterer C (2007) Identification of selective sweeps using a dynamically adjusted number of linked microsatellites. Genetics 175, 207-218.
• Nolte V, Schlötterer C (2008) African Drosophila melanogaster and D. simulans populations have similar levels of sequence variability, suggesting comparable effective population sizes. Genetics 178, 405-412.
• Nolte V, Weigel D, Schlötterer C (2008) The impact of shared ancestral variation on hybrid male lethality--a 16 codon indel in the Drosophila simulans Lhr gene. J Evol Biol 21, 551-555.
• Torres TT, Metta M, Ottenwälder B, Schlötterer C (2008) Gene expression profiling by massively parallel sequencing. Genome Res 18, 172-177.
• Nunes DM, Nolte, V, Schlötterer C (2008) Nonrandom Wolbachia infection status of Drosophila melanogaster strains with different mtDNA haplotypes. Mol Biol Evol 25, 2493-2498.