Welcome to the web home of the Computational and Analytical Molecular Evolution Laboratory (Stoltzfus group) at CARB. Use the navigation table at the top of this page to find what you want.
Mutation and evolutionary genetics
Contrary to the Modern Synthesis view, biases in mutation
(e.g., see bubble plot of mutation rates at right) bias the course of evolution, even adaptive evolution
(see Rokyta, et al.),
in a predictable manner. This causal influence raises many questions:
- What is the population-genetic mechanism (see Yampolsky and Stoltzfus, 2001)?
- How did neo-Darwinists overlook this mechanism, claiming instead that internal causes of direction are impossible (Stoltfus, 2006a)?
- Can we tease apart mutational effects from fitness effects? (Yampolsky and Stoltzfus, 2005)
- What kinds of mutation biases exist and what is their impact?
- Can they cause long-term patterns or trends (Stoltzfus, 2006b)?
- How often are mutational effects wrongly attributed to "function"?
- What about developmental biases in phenotypic variation (Stoltzfus, 2006a)?
Our research in this vital and exciting area includes both theoretical modeling and data analysis. Ongoing work addresses the alleged adaptedness of the genetic code (Stoltzfus and Yampolsky, accepted),
and the challenges for genomics (Stoltzfus, in prep). |
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The evolution of introns and intron-containing genes
How did our genomes come to contain hundreds of thousands of introns?
As shown by Stoltzfus, et al. (1997),
when comparing intron-containing genes from diverse eukaryotic species, the
diversity in intron sites is not mainly due to inheritance and loss of primordial
introns or to "intron sliding", but to the addition of introns to genes during
eukaryotic evolution. Thus the original "introns-early" view in which all or most
introns date back to a primordial ancestor cannot be correct.
However, a coherent alternative theory that accounts for non-random patterns
in the distribution of introns (e.g., phase bias)
has yet to be established. A major step forward came in 2004, when Qiu, et al.
(Stoltzfus group) and Sverdlov, et
al. (Koonin group at NCBI) provided rigorous evidence for Dibb's
"protosplice" hypothesis that introns are gained with
nucleotide sequence preferences (see the logo at left). Our ongoing
research uses sequence analysis, database tools, and computer modelling
to evaluate the causes for this pattern, and its consequences for the
distribution of introns with respect to reading frame phase and with respect to
protein structural features. Recent work includes a demonstration that sequence-based models largely explain non-uniformity in the positions of introns relative to protein structure (De Kee, Gopalan and Stoltzfus, MBE), and a demonstration, using the tubulin gene family, of the inadequacy of simple methods of character reconstruction to account for intron data (Gopalan and Stoltzfus, in prep) |
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Bioinformatics Tools for Molecular Evolution Research
Development of software tools is an ongoing process in our research group. Most such tools relate to a specific project and have a short lifespan. However, a long-term goal is to develop a database system to automate the evolutionary analysis of gene family data. This system has two main parts: a software pipeline that extracts and collates sets of gene family data extracted from sequence databases, and a database system that provides for phylogenetic inference, querying and analysis. Some of the fruits of these efforts are Bio::NEXUS, our NEXUS applications programming interface in Perl, described by Hladish, et al., 2007, the Nexplorer server interface described by Gopalan, et al., and the thousands of sequence family data sets that can be accessed via Nexplorer.
As of 2006, we are doing some of this work in conjunction with the Evolutionary Informatics Working Group supported by the National Evolutionary Synthesis Center (aka "NESCent"). This working group, headed by Stoltzfus and Rutger Vos (of Bio::Phylo fame), has a mandate to improve interoperability in comparative analysis.
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And other topics, some related
- More realistic models of protein evolution
- Evolution on rough fitness landscapes
- Integrating mutation-and-altered-development into evolutionary theory
- RNA editing, gene scrambling, and other strange things
- Duplicate gene evolution
- Flying-Spaghetti-Monster (FSM) Theory
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