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. 2023 Mar 2;223(3):iyac186.
doi: 10.1093/genetics/iyac186.

Telomeres are shorter in wild Saccharomyces cerevisiae isolates than in domesticated ones

Melania D'Angiolo  1 , Jia-Xing Yue  1   2 , Matteo De Chiara  1 , Benjamin P Barré  1 , Marie-Josèphe Giraud Panis  1 , Eric Gilson  1   3 , Gianni Liti  1
Affiliations

Telomeres are shorter in wild Saccharomyces cerevisiae isolates than in domesticated ones

Melania D'Angiolo et al. Genetics. .

Abstract

Telomeres are ribonucleoproteins that cap chromosome-ends and their DNA length is controlled by counteracting elongation and shortening processes. The budding yeast Saccharomyces cerevisiae has been a leading model to study telomere DNA length control and dynamics. Its telomeric DNA is maintained at a length that slightly varies between laboratory strains, but little is known about its variation at the species level. The recent publication of the genomes of over 1,000 S. cerevisiae strains enabled us to explore telomere DNA length variation at an unprecedented scale. Here, we developed a bioinformatic pipeline (YeaISTY) to estimate telomere DNA length from whole-genome sequences and applied it to the sequenced S. cerevisiae collection. Our results revealed broad natural telomere DNA length variation among the isolates. Notably, telomere DNA length is shorter in those derived from wild rather than domesticated environments. Moreover, telomere DNA length variation is associated with mitochondrial metabolism, and this association is driven by wild strains. Overall, these findings reveal broad variation in budding yeast's telomere DNA length regulation, which might be shaped by its different ecological life-styles.

Keywords: S. cerevisiae; domestication; evolution; natural variation; population genomics; telomere; yeast.

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Figures

Fig. 1.
Fig. 1.
Overview of the YeaISTY workflow. a) Paired-end reads are scanned for telomeric repeats (either C{1,3}A or TG{1,3}). Reads containing a stretch of telomeric repeats longer or equal to 40 bp are retained. All the reads (retained and nonretained) are mapped to a modified reference genome. The mapping position of retained reads and their paired ones is used to classify them as ITS-derived or telomeric. The amount of ITS-derived and telomeric reads is then used to infer ITS content and telomere length, while coverage data are used to infer the copy number of Y′ elements. b) XhoI digestion of genomic DNA from representative strains of 17 S. cerevisiae lineages identified in Peter et al. (2018). Genomic DNA is probed with radioactively-labeled telomeric TG1–3 repeats. The black line denotes TRFs resulting from the digestion of a Y′ element. No TRFs were detected for the representatives of the Sake (25.S-CLN) and Mosaic beer (07.M-AAB) clades. The first lane shows a 200 bp DNA ladder used to derive the size of each TRF. c) Comparison of telomere length measured by teloblot and YeaISTY. Values in the plot are corrected for the 4-fold YeaISTY underestimation bias. Despite we estimated TL of S288C from sequencing data derived from Yue et al. (2017), we did not introduce this value in the plot as it derived from another sequencing batch and had a different underestimation rate. The Sake (CLN) and Mosaic beer (AAB) representatives were excluded from the comparison. The inset shows the correlation excluding the outlier with extremely long telomeres (1.2.C-ADI).
Fig. 2.
Fig. 2.
TL variation in 706 S. cerevisiae isolates. Telomere length of the phylogenetic lineages in the 706 S. cerevisiae collection (Peter et al. 2018). Colors code represents the clade classification (domesticated, wild or unassigned), as reported in De Chiara et al. (2022). Clades are assigned as wild or domesticated based on the environmental origin of the isolates dominating (>66%) in the clade. They were labeled “Unassigned” if the threshold criterion was not passed. The order of clades on the x axis is the same as in Peter et al. (2018). In the box plots, horizontal lines denote the median, top and bottom hinges denote the IQR, whiskers denote maximum and minimum values within upper and lower hinges ± 1.5 × IQR. Numbers on top represent the number of isolates in each clade.
Fig. 3.
Fig. 3.
TL variation in domesticated and wild yeasts. a) Telomere length of domesticated, wild and unassigned isolates. Isolates classification is as in Fig. 2. b) Telomere length of domesticated isolates, divided in groups based on their substrate of isolation. “Domesticated-anthropic” are strains isolated from fermentation processes; “Domesticated-feral” are strains isolated from natural environments; “Human-associated” comprises strains isolated from the human body; “Unknown” comprises strains whose substrate of isolation is unknown. c) Telomere length of S. cerevisiae vs S. paradoxus strains from the SGRP. S. cerevisiae strains are further subdivided in groups based on their substrate of isolation. Box plots within in the violin plots are as in Fig. 2. Numbers on top represent the number of isolates in each group. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns = nonsignificant.
Fig. 4.
Fig. 4.
TL genetic variants. a) Manhattan plot showing the position of the GWAS variants across the genome. 20 variants are beyond the genome-wide significance threshold (P < 0.05, dashed line). SNVs: single nucleotide variants; CNVs: copy number variants. Numbers in brackets denote the number of variants contained in that group. For simplicity, only the first 1,000 tested variants are shown in the plot. b) Fraction of TLM and non-TLM genes carrying predicted loss-of-function mutations in euploid diploid domesticated (n = 350) and wild (n = 49) isolates (total n = 399). Isolates classified as unassigned (n = 156) were not considered in this analysis. TLM genes are further subdivided into the ones conferring shorter vs longer telomeres when deleted. The dashed line indicates the fraction of wild strains in the 399 S. cerevisiae collection (12%).
Fig. 5.
Fig. 5.
TL and mitochondrial phenotypes. a) Mitochondrial activity in YPD of the phylogenetic lineages in the 555 S. cerevisiae collection. Isolates classification is as in Fig. 2. Box plots are as in Fig. 2. FU = fluorescence units. b, c) Associations between mitochondrial activity in YPD and telomere length in the 555 S. cerevisiae collection (left panel) and in the subset of wild isolates (n = 49; right panel). Each point represents a single isolate and the lines represent linear regression functions before (green) and after (pink) correction for phylogenetic signal. The association is significant when considering both the whole dataset (n = 555) and only the wild isolates. The other 3 mitochondrial phenotypes (mitochondrial activity and volume in YPD and YPEG) show similar trends but they are not shown for simplicity, while the copy number of mitochondrial DNA negatively correlates with telomere length (P < 0.05). Orig. regr = original regression.
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