# Genome evolution, commensalism and pathogenicity in the diploid fungus Candida albicans

> **NIH NIH P20** · BROWN UNIVERSITY · 2020 · $265,866

## Abstract

Fungal pathogens exhibit considerable genetic plasticity, with both microvariation and chromosomelevel 
rearrangements frequently enabling adaptation to host and environmental pressures. Several genera 
of fungi are important human pathogens, with invasive fungal infections responsible for the death of 
approximately 1.5 to 2 million people worldwide each year. Candida species are the most prominent cause 
of invasive fungal disease in the US, with the major protagonist being Candida albicans. This is a highly 
adaptive species with the ability to occupy diverse niches in the human body, either as a benign 
commensal or as an invasive opportunistic pathogen. 
This project seeks to define microevolution of C. albicans diploid genomes over relatively short time 
scales during growth in vitro or during infection of the mammalian host. The C. albicans genome consists of 
eight heterozygous chromosomes that can undergo de novo mutation, loss of heterozygosity (LOH), or 
large scale rearrangements including variations in chromosome copy number. To define microevolutionary 
changes, clinical isolates will be sequenced before and after passaging in different murine models of 
infection and the full spectrum of genetic changes determined by deep-sequencing analysis. Preliminary 
experiments have established higher mutation rates during mammalian infection and that genome evolution 
in C. albicans is shaped by strong purifying selection. Analyses reveal that ‘micro-scale’ changes are key 
drivers of microevolution, including frequent de novo mutations and short LOH events. This project looks to 
build on these studies and to use C. albicans as a model species for understanding the generation of 
genetic diversity in a heterozygous diploid eukaryote. 
The proposed experiments will address how genetic change drives host adaptation, including changes 
in fitness and virulence. Gene expression changes will be examined before and after passaging and 
mechanisms underlying host adaptation will be genetically dissected. Exciting preliminary data suggests 
that LOH and aneuploidy are important mechanisms by which C. albicans readily adapts to host niches. 
This proposal also seeks to develop new tools, including methods to define fungal growth rates in the 
mammalian host, phasing of diploid genomes, as well as bioinformatic pipelines for high resolution analysis 
of heterozygous genomes. These experiments will provide a detailed insight into how C. albicans adapts to 
its host, and the capacity for genomic variation to drive microevolution.

## Key facts

- **NIH application ID:** 10350145
- **Project number:** 5P20GM109035-05
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Iuliana Veronica Ene
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $265,866
- **Award type:** 5
- **Project period:** 2020-03-01 → 2021-08-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10350145

## Citation

> US National Institutes of Health, RePORTER application 10350145, Genome evolution, commensalism and pathogenicity in the diploid fungus Candida albicans (5P20GM109035-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10350145. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*