Impact of Chromosomal Inversions on the Yeast DAL Cluster

Abstract

Chromosomal rearrangements occur readily in nature and are a major reshaping force during genome evolution. Such large scale modifications are usually deleterious causing several fitness defects, but sometimes can confer an advantage and become adaptive. For example the DAL metabolic cluster in yeast was assembled in recent evolutionary times in the Hemiascomycetes lineage, through a set of rearrangements that brought together the genes involved in the allantoin degradation pathway. In eukaryotes, the existence of physical clustering of genes with related functions supports the notion that neighbouring ORFs tend to be co-expressed and that the order of genes along the chromosomes may have biological significance, rather than being random as previously believed. In this study, we investigate the phenotypic effect that inversions have on the DAL gene cluster, expressed during nitrogen starvation. In all Saccharomyces “sensu stricto” species the order of the DAL cluster is conserved, while in the “sensu lato” species Naumovia castellii, which grows significantly worse than S. cerevisiae on allantoin, the cluster includes two nested inversions encompassing three DAL genes. We constructed several inverted and non-inverted S. cerevisiae strains possessing different inversions including those to mimic the configuration of the N. castellii DAL cluster. We showed that the inversion of DAL2 lower its own expression and reduces yeast fitness during nitrogen starvation. This rearrangement also altered the expression of the neighbouring genes DAL1 and DAL4. Moreover, we showed that the expression of the DAL4 anti-sense transcript (SUT614) does not change upon inversions of DAL2 and therefore is unlikely to be involved in its regulation. These results show that the order of the DAL cluster has an impact on the phenotype and gene expression, suggesting that these rearrangements may have been adaptive in the “sensu stricto” group in relation to the low availability of nitrogen in the environment.

History of genome editing in yeast

“…Chromosomal rearrangements such as translocations and inversions are known to affect the mitotic and meiotic fitness of different yeast species (Avelar et al, ; Colson, Delneri, & Oliver, ; Naseeb et al, ; Naseeb & Delneri, ). It has been shown that S. cerevisiae strains carrying single gene inversions can cause fitness defects in nutrient‐limited media (Naseeb & Delneri, ). However, large chromosomal inversions in S. cerevisiae can be either lethal or neutral depending upon the environmental conditions (Naseeb et al, ).…”

Naumovozyma castellii: an alternative model for budding yeast molecular biology

“…cerevisiae and encodes the allantoin catabolism pathway. Allantoin is the degradation product of purines, but the enzymes for degrading purine ring systems is missing in yeasts (Cooper et al ., ; Naseeb and Delneri, ; Wong and Wolfe, ). Instead, allantoin is imported from the environment.…”

“…The allantoin degradation pathway also includes genes for allantoin racemase ( DCG1 ) and an isoform of malate synthases ( DAL7 ). This cluster of six DAL genes is located in a 9.4 kb region near the right telomere of chromosome IX (Naseeb and Delneri, ; Wong and Wolfe, ). The DAL cluster present in N .…”

“…The DAL cluster present in N . castellii differs in the gene order by two nested gene inversions compared with the Saccharomyces sensu stricto group (Naseeb and Delneri, ; Wong and Wolfe, ). These inversions may be responsible for the significant fitness impairment of N .…”

“…These inversions may be responsible for the significant fitness impairment of N . castellii when grown in nitrogen‐poor medium containing allantoin (Naseeb and Delneri, ; Wong and Wolfe, ).…”