The Evolution of Genome Architecture

It is commonly assumed that a causal link exists between complexity at the genomic and organismal levels. However, using population-genetic principles as a guide to understanding the evolution of duplicate genes, introns, mobile-genetic elements, and regulatory-region complexity, our work is advancing the hypothesis that much of eukaryotic genome complexity initially evolved as a passive indirect response to reduced population size (relative to the situation in prokaryotes). 

• The Paramecium model system. One of the primary goals of our work on gene duplication is to explain the shortcomings of the classical model, which postulates that the usual fate of a duplicated gene is either conversion to a nonfunctional pseudogene or acquisition of a new function. We promoted the alternative view that duplicate genes are frequently preserved through a partitioning of functions of ancestral genes (subfunctionalization), rather than by the evolution of new functions. Our empirical work in this area is now focused on ciliates within the Paramecium aurelia complex, which arose as a cryptic species radiation following two whole-genome duplication events (dating to nearly a billion years ago). Sequencing the complete genomes of the members of this lineage, along with the pre-duplication outgroup species, is revealing the degree to which specific members of duplicate-gene pairs are lost/preserved in parallel or divergently resolved in sister taxa, and high-throughput work in transcriptomics and intracellular spatial proteomics is helping reveal the mechanisms of subfunctionalization. We are now attempting to ascertain the regulatory vocabulary (transcription-factor binding sites) of the members of this complex, how this diverges over time. Relative to other unicellular eukaryotes and despite their cellular complexity, Paramecium genomes have remarkably little intergenic and intronic DNA, and extraordinarily simple modes of transcription initiation. 

• The origin of introns. Our work on intron evolution is focused on the hypothesis that newly arisen introns are typically mildly deleterious. A major goal is to understand how introns eventually came to be integrated into fundamental aspects of gene-transcript processing. Empirical work in this area is being pursued with populations of Daphnia, which have revealed an unprecedented level of intron gain (to the extent that presence/absence of polymorphisms, as well as parallel intron gains, can be found within populations). We hope that this work will eventually yield an answer to the long-term mystery as to the origins of introns.

• Molecular drive and coevolution of organelle- and nuclear-encoded proteins. Mitochondrial genomes typically have high mutation rates and lack recombination. As a consequence, mutation-accumulation in the few genes contained within these genomes can impose pressure for the establishment of compensatory mutations in interacting proteins encoded in the nuclear genome. In addition to developing theory for molecular coevolution, we are pursuing empirical work on the comparative structure of mitochondrial and cytosolic ribosomes, as determined by cryo EM.