Location

I am currently a graduate student in Paul Schmidt’s lab at the University of Pennsylvania.

E-mail
Annalise Paaby

Lab phone
(215) 898-7356

Mailing address
Department of Biology
University of Pennsylvania
433 S. University Avenue
Philadelphia, PA 19104-6018

Research

Lifespan evolution

My dissertation work examines microevolutionary forces in natural populations of the fruit fly Drosophila melanogaster.

In particular, I study the evolution of lifespan. Flies from high latitude populations live longer than flies from low latitute populations; high latitude flies also show lower fecundity, higher stress tolerance, and a suite of other correlated life history traits. Our lab and others have shown that genetics underly these variations in phenotype. My work takes a gene-targeted approach to investigate how environmental variation imposes differential selection pressure on these life history traits to drive lifespan evolution.

Aging genes

Multiple candidate genes for aging have been identified in D. melanogaster, typically by extended longevity mutant phenotypes. Despite their long lifespan, aging gene mutants are not especially fit: most have compromised reproductive success, which explains why functional alleles that promote aging persist in the wild. Because genes that regulate lifespan are pleiotropic and because different environments may favor different life history strategies, genetic variation at some aging loci may be maintained by selection. My work characterizes naturally-occurring allelic variation at several aging loci, by addressing two general questions:

1) Do aging genes show patterns of allelic variation across geography? Different environments exert different selection pressures, and a pattern of nucleotide variation across geography can indicate selection and identify possible functional polymorphisms.

2) Do candidate functional polymorphisms within aging loci demonstrate differences in phenotype? Identifying a specific nucleotide variant that affects phenotype can shed light on how genotypes are translated into phenotypes, and testing for effects on multiple traits can explain which traits are visible to selection.

InR and chico

Reduction of insulin signaling promotes lifespan in flies, worms and mice, and the pathway can be disrupted at multiple independent points to achieve lifespan extension. However, members of the pathway may not be equally responsive to selection. We performed a survey for allelic variation at two insulin signaling genes and found significant patterns of polymorphism and divergence at the insulin receptor, InR, but not at the receptor substrate, chico. In addition to showing evidence of protein evolution since D. melanogaster shared a common ancestor with its sister species D. simulans two million years ago, InR also showed a pattern of polymorphism across latitude that suggests a contemporaneous response to selection. On both the North American and Australian continents, we and our collaborators found that the most common haplotype of an amino acid indel polymorphism at InR increased with latitude while the second most common haplotype decreased with latitude. This pattern suggests that alternate alleles are being maintained by alternate life history regimes across a heterogeneous environment. We are currently testing this amino acid polymorphism for functional significance.

methuselah

The gene methuselah (mth) was the first aging gene identified in D. melanogaster. Later work showed that a haplotype, comprised of five SNPs and maintained by linkage disequilbrium across the mth locus, exhibits a cline in frequency across the latitudinal gradient of the U.S. east coast that is suggestive of selection. Using a quantitative complementation test, I tested the functional significance of eight wild-derived mth alleles and found differences in lifespan, fecundity and tolerance to oxidative stress. We hypothesize that an unknown polymorphism at mth is contributing to differences in life history and is being maintained by alternate selection regimes across the latitudinal gradient. (Results are summarized in this PLoS One paper.) I am currently examining the remainder of the mth locus, including 5′ and 3′ UTRs, in order to more fully characterize the naturally-occurring variation and identify the functional polymorphism.

Publications

In Preparation

Paaby, A.B., M.J. Blacket, A.A. Hoffmann and P.S. Schmidt. In Preparation. Parallel independent clines on two continents suggest adaptive variation at the Drosophila insulin receptor. Genetics.

Published / In Press:

Schmidt, P.S. and A.B. Paaby. 2008. Reproductive diapause and life history clines in North American populations of Drosophila melanogaster. Evolution 62(5): 1204-1215. HTML PDF

Paaby, A.B. and P.S. Schmidt. 2008. Functional significance of allelic variation at methuselah, an aging gene in Drosophila. PLoS ONE 3(4): e1987. HTML (Cited as a F1000 “Must Read”)

Schmidt, P.S., A.B. Paaby and M.S. Heschel. 2005. Genetic variance for diapause expression and associated life histories in Drosophila melanogaster. Evolution 59(12): 2616-2625. HTML PDF

Walters, J.P., C.X. Muñoz, A.B. Paaby and S. DiNardo. 2005. Serrate-Notch signaling defines the scope of the initial denticle field by modulating EGFR activation. Developmental Biology 286: 415-426. HTML PDF

CV in brief

My complete CV (PDF) can be downloaded here.

Education
Swarthmore College, B.A. in Biology, 2000
University of Pennsylvania, anticipated Ph.D. in Biology, 2009

Professional experience
Lab technician, University of Pennsylvania, Department of Cell and Developmental Biology, 2000-2002
Lab technician, University of Pennsylvania, Department of Biology, 2002-2003

Teaching experience (guest lecturer)
Evolutionary Biology, Spring 2007
Evolutionary Biology, Spring 2008

Teaching experience (teaching assistant)
Human biology and reproduction, Fall 2003
Introductory Biology, Spring 2004
Advanced Introductory Biology, Fall 2004
Introductory Biology, Spring 2005
Statistics for Biologists, Fall 2005
Evolutionary Biology, Spring 2006
Evolutionary Biology, Spring 2007
Evolutionary Biology, Spring 2008

Awards
Glenn Foundation/AFAR Scholarship, 2004
Binns-Williams Scholarship, University of Pennsylvania, 2005
Binns-Williams Scholarship, University of Pennsylvania, 2006
University of Pennsylvania SAS Dissertation Completion Fellowship, 2008

Website

I author the blog thinkevolution.net, which explores scientific and popular issues in evolutionary biology.