Rec-8 dimorphism affects longevity, stress resistance and X-chromosome nondisjunction in C. elegans, and replicative lifespan in S. cerevisiae

Srinivas Ayyadevara, çagdas Tazearslan, Ramani Alla, James C. Jiang C., S. Michal Jazwinski, Robert J Shmookler Reis

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A quantitative trait locus (QTL) in the nematode C. elegans, "lsq4," was recently implicated by mapping longevity genes. QTLs for lifespan and three stress-resistance traits coincided within a span of <300 kbp, later narrowed to <200 kbp. A single gene in this interval is now shown to modulate all lsq4-associated traits. Full-genome analysis of transcript levels indicates that lsq4 contains a dimorphic gene governing the expression of many sperm-specific genes, suggesting an effect on spermatogenesis. Quantitative analysis of allele-specific transcripts encoded within the lsq4 interval revealed significant, 2- to 15-fold expression differences for 10 of 33 genes. Fourteen "dual-candidate" genes, implicated by both position and expression, were tested for RNA-interference effects on QTL-linked traits. In a strain carrying the shorter-lived allele, knockdown of rec-8 (encoding a meiotic cohesin) reduced its transcripts 4-fold, to a level similar to the longer-lived strain, while extending lifespan 25-26%, whether begun before fertilization or at maturity. The short-lived lsq4 allele also conferred sensitivity to oxidative and thermal stresses, and lower male frequency (reflecting X-chromosome non-disjunction), traits reversed uniquely by rec-8 knockdown. A strain bearing the longer-lived lsq4 allele, differing from the short-lived strain at <0.3% of its genome, derived no lifespan or stress-survival benefit from rec-8 knockdown. We consider two possible explanations: high rec-8 expression may include increased "leaky" expression in mitotic cells, leading to deleterious destabilization of somatic genomes; or REC-8 may act entirely in germ-line meiotic cells to reduce aberrations such as non-disjunction, thereby blunting a stress-resistance response mediated by innate immunity. Replicative lifespan was extended 20% in haploid S. cerevisiae (BY4741) by deletion of REC8, orthologous to nematode rec-8, implying that REC8 disruption of mitotic-cell survival is widespread, exemplifying antagonistic pleiotropy (opposing effects on lifespan vs. reproduction), and/or balancing selection wherein genomic disruption increases genetic variation under harsh conditions.

Original languageEnglish (US)
Article numberArticle 211
JournalFrontiers in Genetics
Volume5
Issue numberAUG
DOIs
StatePublished - 2014

Fingerprint

X Chromosome
Saccharomyces cerevisiae
Alleles
Quantitative Trait Loci
Genome
Genes
Chromosome Mapping
Haploidy
Spermatogenesis
RNA Interference
Fertilization
Innate Immunity
Germ Cells
Reproduction
Spermatozoa
Cell Survival
Oxidative Stress
Hot Temperature
Gene Expression

Keywords

  • C. elegans
  • Genetics of aging
  • Lifespan
  • Longevity
  • Meiotic cohesin
  • Rec-8 or REC8
  • S. cerevisiae
  • Stress resistance

ASJC Scopus subject areas

  • Genetics
  • Molecular Medicine
  • Genetics(clinical)

Cite this

Rec-8 dimorphism affects longevity, stress resistance and X-chromosome nondisjunction in C. elegans, and replicative lifespan in S. cerevisiae. / Ayyadevara, Srinivas; Tazearslan, çagdas; Alla, Ramani; Jiang C., James C.; Jazwinski, S. Michal; Reis, Robert J Shmookler.

In: Frontiers in Genetics, Vol. 5, No. AUG, Article 211, 2014.

Research output: Contribution to journalArticle

Ayyadevara, Srinivas ; Tazearslan, çagdas ; Alla, Ramani ; Jiang C., James C. ; Jazwinski, S. Michal ; Reis, Robert J Shmookler. / Rec-8 dimorphism affects longevity, stress resistance and X-chromosome nondisjunction in C. elegans, and replicative lifespan in S. cerevisiae. In: Frontiers in Genetics. 2014 ; Vol. 5, No. AUG.
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AU - Reis, Robert J Shmookler

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N2 - A quantitative trait locus (QTL) in the nematode C. elegans, "lsq4," was recently implicated by mapping longevity genes. QTLs for lifespan and three stress-resistance traits coincided within a span of <300 kbp, later narrowed to <200 kbp. A single gene in this interval is now shown to modulate all lsq4-associated traits. Full-genome analysis of transcript levels indicates that lsq4 contains a dimorphic gene governing the expression of many sperm-specific genes, suggesting an effect on spermatogenesis. Quantitative analysis of allele-specific transcripts encoded within the lsq4 interval revealed significant, 2- to 15-fold expression differences for 10 of 33 genes. Fourteen "dual-candidate" genes, implicated by both position and expression, were tested for RNA-interference effects on QTL-linked traits. In a strain carrying the shorter-lived allele, knockdown of rec-8 (encoding a meiotic cohesin) reduced its transcripts 4-fold, to a level similar to the longer-lived strain, while extending lifespan 25-26%, whether begun before fertilization or at maturity. The short-lived lsq4 allele also conferred sensitivity to oxidative and thermal stresses, and lower male frequency (reflecting X-chromosome non-disjunction), traits reversed uniquely by rec-8 knockdown. A strain bearing the longer-lived lsq4 allele, differing from the short-lived strain at <0.3% of its genome, derived no lifespan or stress-survival benefit from rec-8 knockdown. We consider two possible explanations: high rec-8 expression may include increased "leaky" expression in mitotic cells, leading to deleterious destabilization of somatic genomes; or REC-8 may act entirely in germ-line meiotic cells to reduce aberrations such as non-disjunction, thereby blunting a stress-resistance response mediated by innate immunity. Replicative lifespan was extended 20% in haploid S. cerevisiae (BY4741) by deletion of REC8, orthologous to nematode rec-8, implying that REC8 disruption of mitotic-cell survival is widespread, exemplifying antagonistic pleiotropy (opposing effects on lifespan vs. reproduction), and/or balancing selection wherein genomic disruption increases genetic variation under harsh conditions.

AB - A quantitative trait locus (QTL) in the nematode C. elegans, "lsq4," was recently implicated by mapping longevity genes. QTLs for lifespan and three stress-resistance traits coincided within a span of <300 kbp, later narrowed to <200 kbp. A single gene in this interval is now shown to modulate all lsq4-associated traits. Full-genome analysis of transcript levels indicates that lsq4 contains a dimorphic gene governing the expression of many sperm-specific genes, suggesting an effect on spermatogenesis. Quantitative analysis of allele-specific transcripts encoded within the lsq4 interval revealed significant, 2- to 15-fold expression differences for 10 of 33 genes. Fourteen "dual-candidate" genes, implicated by both position and expression, were tested for RNA-interference effects on QTL-linked traits. In a strain carrying the shorter-lived allele, knockdown of rec-8 (encoding a meiotic cohesin) reduced its transcripts 4-fold, to a level similar to the longer-lived strain, while extending lifespan 25-26%, whether begun before fertilization or at maturity. The short-lived lsq4 allele also conferred sensitivity to oxidative and thermal stresses, and lower male frequency (reflecting X-chromosome non-disjunction), traits reversed uniquely by rec-8 knockdown. A strain bearing the longer-lived lsq4 allele, differing from the short-lived strain at <0.3% of its genome, derived no lifespan or stress-survival benefit from rec-8 knockdown. We consider two possible explanations: high rec-8 expression may include increased "leaky" expression in mitotic cells, leading to deleterious destabilization of somatic genomes; or REC-8 may act entirely in germ-line meiotic cells to reduce aberrations such as non-disjunction, thereby blunting a stress-resistance response mediated by innate immunity. Replicative lifespan was extended 20% in haploid S. cerevisiae (BY4741) by deletion of REC8, orthologous to nematode rec-8, implying that REC8 disruption of mitotic-cell survival is widespread, exemplifying antagonistic pleiotropy (opposing effects on lifespan vs. reproduction), and/or balancing selection wherein genomic disruption increases genetic variation under harsh conditions.

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