The Anderson lab is broadly interested in how genetic diversity arises and contributes to organismal adaptation and survival. To address these questions, we rely primarily on investigation of the common human commensal and opportunistic human fungal pathogen Candida albicans using a combination of experimental and computational approaches. This single-celled eukaryote is easily cultivated in the lab, has a compact and diploid genome, can be manipulated with a vast assortment of molecular tools, and has relevance to treating humans suffering from fungal disease. Mucosal candidiasis is caused by overgrowth of C. albicans in its commensal niche. If C. albicans accesses the bloodstream, it can lead to systemic disease with high rates of mortality. C. albicans therefore provides a model for investigaiton of basic biological principles with clear benefit to human health.
Gene family expansions
Comparison between pathogen and non-pathogen Candida species highlighted the expansion of virulence factors such as lipases, adhesins, and proteases in species that cause disease. Among organisms in the Candida paraphyletic group, C. albicans is the most clinically relevant species. While it has expanded its repertoire of virulence factors, a poorly characterized set of paralogous genes called the telomere-associated (TLO) gene family has undergone the most dramatic expansion froma single copy in most Candida species to 14 copies in the C. albicans genome reference strain. TLO genes usually reside in the subtelomeres of the C. albicans chromosomes where they are able to evolve and recombine with each other in as short as once every 5000 generations (1:5000 cells has a new TLO gene!) All TLO genes encode the MED2 domain that identifies them as MED2 homologs but can be separated into three groups based on variation in their 3′ end. We now know that these genes encode homologs of the Med2 subunit of the major transcriptional regulatory complex called Mediator. As transcription factors, we know very little about the genes they control or what selective pressure led to the massive expansion of the gene family. We are currently working to understanding if these genes retain redundant functions or have diversified their functions during expansion.
Intraspecies variation in C. albicans
Work from many labs including ours has shown that widespread genetic diversity exists among C. albicans strains. Much of this genetic variation arose through asexual processes of point mutations, loss of heterozygosity, and changes in chromosome copy number. However, we have also been able to demonstrate that an alternate mating program termed parasex has the ability to generate high levels of genetic diversity. This genetic variation can then be acted upon by selection to facilitate C. albicans adaptation to changing conditions in its environment. We are exploring how existing genetic variation in C. albicans isolates from patient samples contributes to the balance between commensalism and pathogenesis. To do this, we have adapted quantitative genetics to C. albicans using the parasexual cycle as a mechanism to mate strains and produce recombinant progeny. We are exploring how variation in single cells and populations leads to improved fitness and working to identify the underlying genes responsible.
Microbiome investigations with Indigenous community partners
Multiple efforts in the lab are directed towards empowering Indigenous communities in North America in areas of research, health, and data sovereignty. A significant portion of the this work is currently directed towards understanding the microbial contributions to health of Tribal people, lands, and waterways. In partnership with a Northern Plains tribe, we are working to identify microbial links to elevated risks of rheumatoid arthiritis (RA) in the community. To better capture the full repertoire of resident microbes, we constructed a metagenomics approach to sequencing the microbial eukaryotes of the human micobiome. This approach is now being applied in our partner community with the focus of RA. Additional work we are beginning seeks to udnerstand how land use practices by the tribe lead to differences in soil microbiome composition with implications for sustained growth of native plants.
