Changes in Gene Expression Associated with Developmental Arrest and Longevity in Caenorhabditis elegans

Abstract

Gene expression in a developmentally arrested, long-lived dauer population of Caenorhabditis elegans was compared with a nondauer (mixed-stage) population by using serial analysis of gene expression (SAGE). Dauer (152,314) and nondauer (148,324) SAGE tags identified 11,130 of the predicted 19,100 C. elegans genes. Genes implicated previously in longevity were expressed abundantly in the dauer library, and new genes potentially important in dauer biology were discovered. Two thousand six hundred eighteen genes were detected only in the nondauer population, whereas 2016 genes were detected only in the dauer, showing that dauer larvae show a surprisingly complex gene expression profile. Evidence for differentially expressed gene transcript isoforms was obtained for 162 genes. H1 histones were differentially expressed, raising the possibility of alternative chromatin packaging. The most abundant tag from dauer larvae (20-fold more abundant than in the nondauer profile) corresponds to a new, unpredicted gene we have named tts-1 (transcribed telomere-like sequence), which may interact with telomeres or telomere-associated proteins. Abundant antisense mitochondrial transcripts (2% of all tags), suggest the existence of an antisense-mediated regulatory mechanism in C. elegans mitochondria. In addition to providing a robust tool for gene expression studies, the SAGE approach already has provided the advantage of new gene/transcript discovery in a metazoan.

Genes that may modulate longevity in C. elegans in both dauer larvae and long-lived daf-2 adults

“…23 and F26E4.9, respectively) were found among the genes with increased transcripts in both dauer larvae and daf-2 adults. Elevated transcript abundance for cytochrome c oxidase subunits in dauer larvae was demonstrated earlier (Jones et al, 2001), but our observation also suggests a role for these genes in adult longevity. The average increase in expression for these genes was 2 to 6-fold (p < 0.001).…”

“…One of the libraries made from RNA extracted from two-day-old dauer larvae has been previously described (Holt and Riddle, 2003;Jones et al, 2001). The second dauer library was prepared from 2-week old dauer larvae.…”

“…The asc-1 gene (Y53F4B.15), a homolog of human activating signal cointegrator-1 (Jung et al, 2002), showed an average 28-fold increase in tags (p < 0.001). The non-coding transcribed telomeric sequence (tts-1) transcript (F09E10.11, reported in Jones et al, 2001) was also found at higher levels (average 57 fold increase) in both daf-2 adults and dauer larvae (p < 0.001). However, the expression level of tts-1 decreased with time in dauer larvae (from 1622 in young dauer to 611 normalized tag counts in 2-week old dauer larvae).…”

Genes regulated by caloric restriction have unique roles within transcriptional networks

“…However, since dauer formation represents a metabolic response to resource limitation that is accompanied by increased longevity, it was suspected that dauerregulated genes could share some network properties with CR-regulated genes. Dauerregulated genes were identified based upon consistencies from two previous microarray experiments (Jones et al, 2001;Wang and Kim, 2003). In particular, 28 dauer-specific genes were identified by intersecting the 358 dauer-enriched genes found by Jones et al (2001) and 540 dauer-enriched genes found by Wang and Kim (2003).…”

“…Dauerregulated genes were identified based upon consistencies from two previous microarray experiments (Jones et al, 2001;Wang and Kim, 2003). In particular, 28 dauer-specific genes were identified by intersecting the 358 dauer-enriched genes found by Jones et al (2001) and 540 dauer-enriched genes found by Wang and Kim (2003). Likewise, 40 nondauer-specfic genes were identified by intersecting the 533 nondauer-specific genes found by Jones et al (2001) and 1984 genes induced during dauer recovery in the study of Wang and Kim (2003).…”