PhD defence: Iñigo Prada-Luengo

Origin and impact of circular DNA on the eukaryotic genomes

Professor, Birgitte Regenberg, KU (main)
Assistant Professor Lasse Maretty, AAU (co-)

Assessment committee
Professor MSO Ole Winther, KU (chairman)
Professor Anders Gorm Pedersen, DTU
Research Director/Team Leader Gilles Charvin, CNRS/IGBMC

Eukaryotic genomes were thought to be organized into highly stable chromosomes with little genetic variation between cells. In the past, various studies have highlighted that besides the canonical chromosomes, eukaryotic genomes contain a plethora of non-chromosomal, circular DNA elements. While modern sequencing technologies provide the potential to investigate their impact, the research community is missing computational methods to deal with the vast amount of data generated by these techniques. Here, I present a new probabilistic method to detect DNA circles from short-read sequencing data, as well as 3 studies exploring the impact of circular DNA on eukaryotes.

The first research project describes Circle-Map, a probabilistic method that guides the realignment of partially mapped reads using discordant reads in the vicinity and it is markedly more accurate than existing approaches. The next chapters involve the exploration of what is the impact of DNA circles on the eukaryotic genomes. I show that eukaryotic genomes contain a myriad of extrachromosomal DNA circles and that gene rich chromosomes form circles more often. Furthermore, I find that some DNA circles are transcriptionally active. Finally, I explore how DNA circles segregate as yeast cells age and divide. I describe that young cells have highly diverse circular DNA populations, but this diversity is substantially diminished on the aged counterparts. Moreover, I found that maintained DNA circles are enriched on replication origins and that circles have flexible inheritance when grown under selection. Taken together, my results show that eukaryotic genomes are rich in circular DNA elements that have the potential to alter the phenotype of the cells carrying them.