homesummary + projectspublicationscvcontact info

1. Population genomics and genome evolution: Do selection and recombination interact to shape patterns of genetic variation and linkage disequilibrium -- via genetic hitchhiking, background selection, and interference effects? Are mutation and recombination coupled? What genomic features facilitate or limit weak selection? What demographic processes shape genetic variation? How do breeding system differences affect genetic variation? How can the complementary information of different marker types be integrated to improve inference of demography and selection?

We are building on our discoveries of hyperdiverse nucleotide variation in the genomes of various Caenorhabditis species in several exciting ways. As a specific example, C. brenneri has the highest molecular diversity of any animal or plant! We are exploiting this to more finely dissect the molecular evolution and function of genes and regulatory elements. This includes the intriguing miRNA genes, as well as other small RNA genes, and genomic features like operons and repetitive DNA.

To better understand how different ongoing forces (recombination, mutation, selection, demography) shape genetic variation in genomes, we are sequencing entire genomes of multiple individuals: population genomics. Our recent discoveries of closely-related species and divergent populations makes genome-scale divergence population genetics analysis an exciting means of quantifying adaptation and other evolutionary processes with unprecedented resolution. In parallel, we are developing a platform for comparative population genetics across the Caenorhabditis genus to study the causes of molecular diversity in a phylogenetic context.

Portions of this work are in collaboration with Bret Payseur (U. Wisconsin), Patrick Phillips (U. Oregon), and Lincoln Stein (OICR).

Codon bias heat map for nematodes
*Molecular hyperdiversity defines populations of the nematode Caenorhabditis brenneri. Dey, A., C.K.W. Chan, C.G. Thomas & A.D. Cutter. 2013. PNAS. 110: 11056-11060. [pdf]
*Genomic signatures of selection at linked sites: unifying the disparity among species. Cutter, A.D. & B.A. Payseur. 2013. Nature Reviews Genetics. 14: 262-274. [pdf]

*Molecular hyperdiversity and evolution in very large populations. Cutter, A.D., R. Jovelin & A. Dey. 2013. Molecular Ecology. 22: 2074-2095. [pdf]
*Integrating phylogenetics, phylogeography and population genetics through genomes and evolutionary theory. Cutter, A.D. 2013. Molecular Phylogenetics and Evolution. In press. [pdf]
*Influence of finite-sites mutation, population subdivision and sampling schemes on patterns of nucleotide polymorphism for species with molecular hyperdiversityCutter, A.D., G.-X. Wang, H. Ai, & Y. Peng. 2012. Molecular Ecology. 21: 1345-1359. [pdf]
*MicroRNA sequence variation potentially contributes to within-species functional divergence in the nematode Caenorhabditis briggsae.
Jovelin, R. & A.D. Cutter. 2011. Genetics. 189: 967-976. [pdf]


2. Genetics of reproductive isolation: What governs the strong male inviability and sterility in inter-species hybrids (Haldane's Rule)? What causes one species to be a better "mom" than another in inter-species hybrids (Darwin's Corollary)? How much genetic variation within-species is there for between-species hybrid viability and fertility? What causes gametic isolation? What genetic differences are responsible for reproductive isolation between species?

Several new projects in the lab aim to exploit Caenorhabditis as a model for speciation genetics. A growing number of Caenorhabditis species pairs have been discovered to be incompletely reproductively isolated from one another: they form viable and fertile hybrids. This permits, for the first time, the ability to use the power of Caenorhabditis to investigate the genetic basis of reproductive isolation. We are exploring this at several levels, from pre-mating factors like the evolution of male responses to mating pheromone to post-mating pre-zygotic factors implicating gametic isolating barriers to post-zygotic incompatibilities that cause inviability and sterility in hybrids. Using powerful tools, including inter-species NIL mapping, in vivo sperm labeling, and gene knockdown by RNAi, we are dissecting the mechanistic and genetic causes of these barriers to gene flow.

*Outbreeding depression with low genetic variation in selfing Caenorhabditis nematodes.
Gimond, C., R. JovelinS. Han, C. Ferrari, A.D. Cutter & C. Braendle. 2013.  Evolution. 67: 3087-3101. [pdf]
Global population genetic structure of Caenorhabditis remanei reveals incipient speciation. Dey, A., Y. Jeon, G.-X. Wang & A.D. Cutter. 2012. Genetics. 191: 1257-1269. [pdf]
*The polymorphic prelude to Bateson-Dobzhansky-Muller incompatibilities. Cutter, A.D. 2012. Trends in Ecology & Evolution. 27: 209-218. [pdf]
Genetic variation for post-zygotic reproductive isolation between Caenorhabditis briggsae and Caenorhabditis sp. 9. Kozlowska, J.L., A.R. Ahmad, E. Jahesh & A.D. Cutter. 2012. Evolution. 66: 1180-1195. [pdf]

3. Genetic basis of natural phenotypic variation: What controls temperature-dependent fecundity variation? What genes underlie behavioral differences among individuals? Do identical complex phenotypes in different species reflect concordant or divergent molecular mechanisms?

We are documenting temperature-dependent traits that differ between latitudinally- and phylogeographically-distinct  strains of C. briggsae. In collaboration with the labs of Scott Baird (Wright State U.) and William Ryu (U. Toronto), we are now interrogating the genetic basis of temperature-related traits with recombinant inbred lines (RILs) to determine the nucleotide changes that cause this natural phenotypic differentiation, thought to reflect local adaptation. In particular, we are attempting to determine the genetic underpinnings of behavior trait variation and fitness differences resulting from problems in gametogenesis. In related work, we are using inter-species NILs to genetically map traits that have diverged between species.

We are starting to expand this work to determine a potential role for small RNAs in C. briggsae fecundity variation (in collaboration with Julie Claycomb at U. Toronto).

 *Temperature-dependent behaviors are genetically variable in the nematode Caenorhabditis briggsae. Stegeman, G.W., M. Bueno de Mesquita, W.S. Ryu & A.D. Cutter. 2013.  Journal of Experimental Biology. 216: 850-858. [pdf]
Temperature-dependent fecundity associates with latitude in Caenorhabditis briggsae. Prasad, A., M. Croydon-Sugarman & A.D. Cutter. 2011.  Evolution. 65:52-63. [pdf]
*Patterns of nucleotide polymorphism distinguish temperate and tropical wild isolates of Caenorhabditis briggsae. Cutter, A.D., M.A. Felix, A. Barriere & D. Charlesworth. 2006.  Genetics. 173: 2021-2031. [pdf]

4. Causes and consequences of breeding system evolution: How many sperm is the optimal number for a hermaphrodite to produce? Has adaptive evolution or relaxed selection generated the "selfing syndrome" in species with hermaphrodites? Under what conditions do different Caenorhabditis species demonstrate competitive advantages? What conditions and traits allow males to persist in androdioecious populations?

Sperm size experimental evolution
Male frequency experimental evolution

We are exploiting the technical tools and  experimental tractability of C. elegans to test specific evolutionary questions with experimental evolution. This work mostly aims to use experiments to explicitly test evolutionary theory. Previous examples include determining how development time and hermaphrodite sperm production rates will affect optimal individual fecundity, and how elevated mutation rate results affects selection against males in populations. We are using similar empirical approaches to better understand niche differentiation among Caenorhabditis species, the genetic basis of ecologically-relevant traits, and the evolution of reproductive isolation.

*Mainstreaming C. elegans in experimental evolution.
Gray, J.C. & A.D. Cutter. 2014. Proceedings B. 281: In press. [pdf]
Experimental evolution of sperm count in protandrous self-fertilizing hermaphrodites. Murray, R.L. & A.D. Cutter. 2011.  Journal of Experimental Biology. 214: 1740-1747.[pdf]
*Evolution of the C. elegans genome. Cutter, A.D., A. Dey & R.L. Murray. 2009. Molecular Biology and Evolution. 26: 1199-1234. [pdf]
Reproductive evolution: symptom of a selfing syndrome. Cutter, A.D. 2008.  Current Biology. 18: R1056-R1058. [pdf]
*Mutation and the experimental evolution of outcrossing in Caenorhabditis elegans. Cutter, A.D. 2005.  Journal of Evolutionary Biology. 18: 27-34. [pdf]


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text & photos 2006-2016 by asher d. cutter. design 2006 by yee-fan sun