Caenorhabditis elegans

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Caenorhabditis elegans

Caenorhabditis elegans is a geographically widespread nematode possibly having origins as far back as the Precambrian era. It is easy to grow and maintain on agar plate with an appropriate bacterial food source such as Escherichia coli. This roundworm has a short lifespan of about 3 days and is modestly to very prolific, laying approximately 300 to 1000 eggs depending on which gender provides fertilization, hermaphrodite or male, respectively. It has been used as a model for molecular biology since 1965 when Sydney Brenner proposed its use in studying a simple nervous system. It has since been used to study eukaryotic systems such as but not limited to: genetics, anatomy, cell linage, germ-line development, sexual development, muscular system, nervous system, and lifespan (Wood 1988).

Kenyon et al. (1993) used this model eukaryote to publish the ground-breaking finding that C. elegans hermaphrodites affected by a mutation in the daf-2 gene were experiencing a doubled lifespan. This research was further supported by Kimura, et al. (1997) who confirmed that the daf-2 gene is involved in regulating the endocrine pathway responsible for switching between reproduction or entering a dauer larval stage that persists indeterminately until harsh conditions and/or lack of available nutrition that normally brings on the stage is alleviated. Kimura, et al. (1997) compared this endocrine pathway as homologous to human increase in longevity induced by fasting and reduction of calorie intake associated with insulin and metabolism regulation. 

C. elegans has five autosomes and one one X chromosome. Two genders occur, either hermaphrodite with a diploid XX chromosome or male with a haploid XO chromosome (Wood 1988). The daf-2 gene is located on chromosome III encompassing bases 3,028,790 through 2,995,753 (sequence Y55D5A.5). It has 23 introns and can be expressed as six different mRNAs depending on end truncation or missing exons. It interacts with four other proteins and 42 other genes (National Center for Biotechnology Information, n.d.). daf-2 is 35 percent identical to the human insulin receptor (Kimura, et al., 1977). Kimura, et al. (1997) further stated, "four sequences (00667, 00622, 00318, and daf-2 - _v SP Ligand-binding Proteolysis TM Tyrosine kinase 00706) were homologous to regions of the mammalian insulin receptor family." (p. 942).

The most interesting point to Kenyon's discovery is that the daf-2 gene regulates whether C. elegans continues to live an extended lifetime in a dauer larval stage or exits into reproductive adulthood. Normally under good conditions C. elegans life cycle is two to three weeks (Fielenbach & Antebi, 2008). While its phenotype is expressed as a dauer larva, C. elegans enters into a form of stasis whereby it can survive harsh environmental conditions (Sommer & Ogawa, 2011) for several months (Fielenbach & Antebi, 2008). Upon environmental cues of better conditions, daf-2 signals an exit from the dauer larval stage (Kimura, et al., 1977) and C. elegans then enters into adulthood, living out a normal lifespan beyond the time spent in the dauer stage (Fielenbach & Antebi, 2008). Thus, the daf-2 gene can regulate for an extended lifetime and the gene has homologs in human genetics. Since Kenyon's discovery there has been a large increase in attention and study regarding this potential for extension of human lifespan. 


References

Fielenbach, N., & Antebi, A. (2008). C. elegans Dauer Formation and the Molecular Basis of Plasticity. Genes & Development, 22(16), 2149–2165. doi.org/10.1101/gad.1701508

Kenyon, C., Chang, J., Gensch, E., Rudner, A., & Tabtiang, R. (1993). A C. elegans Mutant that Lives Twice as Long as Wild Type. Nature, 366(6454), 461-4. doi: 10.1038/366461a0.

Kimura, K. D., Tissenbaum, H. A., Liu, Y., & Ruvkun, G. (1997). daf-2, an Insulin Receptor-Like Gene That Regulates Longevity and Diapause in Caenorhabditis elegans. Science, 277(5328), 942–946. doi: 10.1126/science.277.5328.942 

National Center for Biotechnology Information. (n.d.) Caenorhabditis elegans Essential Gene daf-2.  AceView WormGenes. Retrieved on August 28 from https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=worm&q=daf-2

Sommer, R. & Ogawa, A. (2011). Hormone Signaling and Phenotypic Plasticity in Nematode Development and Evolution. Current Biology, 21(18), 758-766. doi.org/10.1016/j.cub.2011.06.034

Wood, W. (1988). The Nematode Caenorhabditis elegans. Cold Spring Harbor Laboratory Press. Retrieved on August 25, 2022 from https://archive.org/details/nematodecaenorha0000unse/mode/2up

https://wormbase.org//species/c_elegans/gene/WBGene00000898#0-9f-10

https://www.uniprot.org/uniprotkb/Q968Y9/entry



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