Zufall Lab

Molecular and Genome Evolution in Protists

Ciliate Genome Evolution

Our current research focuses on understanding the role of genome architecture in molecular evolution. The study system is ciliates, eukaryotic microbes that contain two nuclei and undergo massive developmental genome processing. The goal of this research is to elucidate the mechanisms and evolutionary implications of developmentally regulated genome rearrangements.

Developmentally regulated genome rearrangements in ciliates

Developmentally regulated genome rearrangements occur in taxonomically diverse eukaryotes, but the most extreme form of this processing is found in ciliates. Ciliates contain two distinct genomes in each cell, one in the germline micronucleus (MIC) and one in the somatic macronucleus (MAC). During development of the MAC from a zygotic nucleus, the genome undergoes a series of processing events including chromosomal fragmentation, excision of internal sequences, and amplification of chromosomes. The extent of chromosomal processing varies among ciliate groups. My research focuses primarily on ciliates with gene-sized chromosomes in their macronuclei, referred to as extensive fragmenters.

Evolution of cis-acting factors in genome processing

The goal of this work is to determine the cis-acting factors controlling genome processing in order to understand the phylogenetic scale at which such mechanisms are conserved. Chromosomal processing in ciliates includes extensive and programmed elimination of internally excised sequences (IESs) from the zygotic nucleus. Studies of IESs, reveal the presence of cis-acting elements in some species, but little conservation of these elements among taxa. All IESs characterized thus far are also bounded by direct repeats, which are variable within and between species. The zygotic genome is also processed by fragmentation of the remaining DNA. This fragmentation can be mediated by cis-acting chromosome breakage sequences (Cbs), which differ among all species examined. By characterizing IESs and Cbs in additional species, we are gaining a better understanding of the mechanisms underlying the evolution of genome processing.

Protein evolution in ciliates

This part of my work aims to assess the effects of extensive genome processing on patterns of molecular evolution in protein coding genes and macronuclear non-coding regions. From the earliest studies of proteins in ciliates, there have been indications that ciliates differ from other eukaryotes in pattern and rate of nucleotide substitution. Phylogenetic analyses based on protein coding genes are often unable to recover a topology of ciliates consistent with analyses based on morphology. This appears to be due to unusually rapid rates of substitution within ciliate lineages. We propose that the unusual genome architecture of ciliates, i.e. separation of germline and somatic nuclei within a single cell and genome processing, allows for increased rates of substitution in protein coding genes in ciliates.

In order to explore the relationship between genome structure and protein evolution, I am studying molecular evolution of protein coding genes with particular emphasis on extensive fragmenters. Current results show elevated rates of amino acid substitution in ciliates in comparison to other eukaryotes, and in extensive fragmenters in comparison to other ciliates. In many of the genes examined thus far, elevated rates of protein evolution are accompanied by the presence of divergent paralogs, with the most divergent paralogs found within species of extensive fragmenters. We are further sampling genes with a variety of functions as well as non-coding regions in order to assess the genome-wide effects of chromosomal processing on molecular evolution.