Peter Andolfatto
Assistant Professor of Biology, UCSD

e-mail: pandolfatto[at]ucsd.edu
lab homepage

     My research interest is in understanding the processes shaping genome variability patterns within and between species. These interests are pursued in four groups of research projects:

1. Comparative population genetics of Drosophila melanogaster and its close relatives.
     Much of my research takes advantage of species in the D. melanogaster species group. D. melanogaster is a well-studied model for genetics for which there are natural populations, a cluster of closely related species, completed genome sequences for several (12) species in this genus as well as an array of tools for classical and molecular genetic manipulations. Together, these features make Drosophila an ideal system for testing and quantifying population genetic models.
     There is considerable interest in using population genetic methods to identify functionally important parts of the genome that distinguish closely related populations or species. However, uncertainty about the demographic history of populations (i.e., their size and structure over time) complicates the interpretation of these population genetic approaches. In particular, it has proven extremely difficult to distinguish the effects of adaptation from those of demographic history. We are using a combination of molecular genomics, population genetics and modeling approaches to establish an adequate demographic null model for several Drosophila species. For example, we are using patterns of linkage disequilibrium (the strength of associations between polymorphic mutations in a population sample) and information about recombination rates to infer the demographic history of Drosophila populations. Several lines of evidence suggest that D. melanogaster has an African origin and has only recently colonised other continents. This work provides a first step towards identifying the forces shaping genome variability patterns and, in particular, the relative importance of adaptation and population size changes during this colonisation.

2. Modes of evolution in different recombination environments.
     In Drosophila, regions of reduced recombination harbour strongly reduced levels of nucleotide diversity. This observation provides evidence for an important role for natural selection in shaping within species genome variability, either as the removal of deleterious alleles by purifying selection and/or the incorporation of newly arising beneficial mutations by positive selection. Population genetics theory predicts that these regions of the genome should be prone to reduced optimal codon usage in genes, an accumulation of slightly deleterious substitutions, slower rates of adaptive amino acid evolution, and higher levels of linkage disequilibrium. We have been exploiting these various population genetic predictions to address questions such as: What is the relative importance of beneficial and deleterious mutations in shaping genome wide polymorphism patterns? To what extent is the efficacy of selection hampered by linkage in the Drosophila genome? We are extending these studies to ask similar questions in a variety of other taxa (e.g. Lepidoptera and Birds) using regions of reduced recombination such as non-recombining sex chromosomes.

3. The population genetics of hybrid zones and speciation.
     A limitation of model organisms like Drosophila is that, in most cases, little is known about their ecology. Other model systems, such as Lepidoptera, provide us with an opportunity to establish the ecological relevance of genetic variation. We are currently developing a Lepidopteran model system to study the genetic architecture of species boundaries. Hybrid zones between partially isolated “species” or locally adapted populations represent the nexus of two opposing forces: natural selection (which promotes species divergence) and gene flow (which prevents species differentiation). Thus, hybrid zones can be used as a natural sieve to identify regions of the genome that distinguish closely related species. Genomic regions under selection in the hybrid zone are expected to show greater differentiation between species than are more distant regions. Patterns of differentiation can therefore yield information about the number and location of the genes underlying species differences.
     We are investigating a hybrid zone between two North-American swallowtail butterfly species, Papilio glaucus and P. canadensis, that differ in a number of diagnostic traits that are ecologically important (including diapause regulation, mimicry and host-plant preferences). On-going genome projects (like the recently completed Bombyx mori genome, and BAC library construction and EST projects for multiple Lepidopteran species) bring Lepidoptera within reach of detailed molecular studies. We are currently developing an EST database for Papilio as well as constructing genetic and physical maps of the Z chromosome for P. glaucus. We plan to survey population-level variability in both species and in transects through the hybrid zone to in an attempt to identify genes on the Z chromosome underlying species differences.

4. The molecular basis of adaptation.
     The relationship between newly arising mutations and phenotyes, not to mention their effect on an individual’s fitness, is poorly understood. Candidate genes underlying adaptations in natural populations provide us with a glimpse of this complex relationship. We are currently studying two candidate genes underlying ecologically important adaptations in two butterfly species to better understand this link between genotype and phenotype. The first is Na,K-ATPase, a gene underlying a host plant adaptation in Danaus plexippus, the Monarch butterfly. Monarch caterpillars feed on Milkweed hostplants and actively sequester their poisonous cardenolides that in turn protect larvae and adults from predators. Cardenolides normally inhibit NaK-ATPase, an enzymatic pump that is crucial for eukaryotic cell function. The incorporation of a single amino acid change in Monarchs protects them from the negative effects of cardenolides. We are investigating the molecular evolution and population genetics of Na,K-ATPase in D. plexippus and its close relatives in the context of their association with milkweed hostplants and their ability to sequester cardenolides. In a second project, we are using a variety of approaches to study selection maintaining a Batesian mimicry phenotype in Papilio glaucus. A large proportion of P. glaucus females (normally a yellow butterfly) opt to paint themselves completely black to closely mimic a poisonous butterfly called the Pipevine Swallowtail. This ecologically important phenotype is determined by a two gene system, one of which is on the W chromosome – a female specific sex chromosome in butterflies. We are developing molecular genetic markers for the W chromosome in P. glaucus to allow population genetic inferences about the mode of selection acting on this female-limited mimicry gene.

     Andolfatto, P., M. Scriber and B. Charlesworth, (2003). Lack of association between mtDNA haplotypes and a female limited mimicry locus in Papilio glaucus. Evolution 57: 305-316.

     Andolfatto, P., and J. D. Wall, (2003). Patterns of linkage disequilibrium across a recombination gradient in African Drosophila melanogaster. Genetics 165:1289- 305

     Halligan, D. L, A. Eyre-Walker, P. Andolfatto and P. D. Keightley (2004). Patterns of evolutionary constraints in intronic and intergenic DNA of Drosophila. Genome Research 14:273-279.

     Haddrill, P. R., K. R. Thornton, B. Charlesworth and P. Andolfatto (2005). Multilocus patterns of nucleotide variability and the demographic and selection history of Drosophila melanogaster populations. Genome Research 15: 790-9.

     Haddrill, P. R., B. Charlesworth and P. Andolfatto ( 2005). Patterns of intron sequence evolution in Drosophila are dependent upon length and GC content. Genome Biology, 6: R67.

     P. Andolfatto ( 2005). Adaptive evolution of non-coding DNA in Drosophila. Nature, 437:1149-1152.

     Thornton, K. R., and P. Andolfatto ( 2005). Approximate Bayesian inference of bottleneck parameters reveals evidence for a recent, severe, bottleneck in non- African populations of Drosophila melanogaster. Genetics, 172:1607-19.

     Bachtrog, D., K. R. Thornton, A. C. Clark and P. Andolfatto (2006). Extensive introgression of mitochondrial DNA relative to nuclear gene flow in the Drosophila yakuba subgroup. Evolution, 60:292-302.

     Thornton, K. R., D. Bachtrog, and P. Andolfatto ( 2006). X-chromosomes and autosomes evolve at similar rates in Drosophila - no evidence for faster-X protein evolution. Genome Research, 16:498-504.

      Peter Andolfatto received a B.Sc. in Biochemistry at Simon Fraser University in 1992 and completed a PhD in Genetics at the University of Chicago in 1999 with a National Science and Engineering Research Council of Canada Graduate Fellowship. He was an European Molecular Biology Organisation Postdoctoral Fellow (1999-2001) and then a Royal Society of Edinburgh Postdoctoral Fellow (2001-2003) at the University of Edinburgh. He has since held a Canada Research Chair in Evolutionary Genetics and was an Assistant Professor of Zoology at the University of Toronto (2003-2004). He was awarded an Alfred P. Sloan Research Fellowship in Molecular and Computational Biology in 2003.