Telomere Length as a Quantitative Trait: Genome-Wide Survey and Genetic Mapping of Telomere Length-Control Genes in Yeast

Abstract

Telomere length-variation in deletion strains of Saccharomyces cerevisiae was used to identify genes and pathways that regulate telomere length. We found 72 genes that when deleted confer short telomeres, and 80 genes that confer long telomeres relative to those of wild-type yeast. Among identified genes, 88 have not been previously implicated in telomere length control. Genes that regulate telomere length span a variety of functions that can be broadly separated into telomerase-dependent and telomerase-independent pathways. We also found 39 genes that have an important role in telomere maintenance or cell proliferation in the absence of telomerase, including genes that participate in deoxyribonucleotide biosynthesis, sister chromatid cohesion, and vacuolar protein sorting. Given the large number of loci identified, we investigated telomere lengths in 13 wild yeast strains and found substantial natural variation in telomere length among the isolates. Furthermore, we crossed a wild isolate to a laboratory strain and analyzed telomere length in 122 progeny. Genome-wide linkage analysis among these segregants revealed two loci that account for 30%–35% of telomere length-variation between the strains. These findings support a general model of telomere length-variation in outbred populations that results from polymorphisms at a large number of loci. Furthermore, our results laid the foundation for studying genetic determinants of telomere length-variation and their roles in human disease.

A genome-wide screen for Schizosaccharomyces pombe deletion mutants that affect telomere length

“…The average telomere length for the deletion mutants was calculated relative to wild-type length, and was grouped into the following categories: slightly short (< 50 bp shorter than wild type, SS); short (50-150 bp, S); very short (> 150 bp, VS); slightly long (< 50 bp longer than wild type, SL); long (50-150 bp, L); and very long (> 150 bp, VL) (Supplementary information, Table S1). Surprisingly, a great majority of the 168 mutants exhibited longer than normal telomeres (151 longer versus 17 shorter), which is the opposite of what has been reported in S. cerevisiae [4,5]. It remains unclear whether this represents a characteristic of telomere regulation in S. pombe.…”

“…gene deletion, has become possible, and genome-wide phenotypic screening for gene function has been widely carried out. For example, Askree et al and Gatbonton et al examined the telomere-length change in about 4 800 non-essential gene deletion mutants of S. cerevisiae, and found that about 250 genes are involved in telomere-length regulation [4,5].…”

“…In addition to the genes that directly affect telomere maintenance or DNA replication, genes such as pst2 and snf5 that are involved in histone modification, chromatin remodeling and nucleosome assembly were also found to affect telomeres (Supplementary information, Table S1). Interestingly, 15 genes of the 168 candidates (as listed in Supplementary information, Table S2), whose deletion changed the telomere length, had their counterparts in S. cerevisiae that have been found to regulate the length of telomeres [4,5]. It requires further validation whether these genes directly contribute to telomere maintenance.…”

Telomere behavior in a hybrid yeast

“…The sequence of telomere repeats, abbreviated C 1-3 A/ TG [1][2][3] , of the related Saccharomyces sensu stricto species are completely conserved. However, the lengths of the telomere repeats vary greatly even among different strains within the same species [1,2].…”

“…However, the lengths of the telomere repeats vary greatly even among different strains within the same species [1,2]. The sequences adjacent to the repeats are also rapidly evolving both within and among Saccharomyces species [3].…”