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Metabolic and Genetic Implications of Survival in Anoxic Drosophila
Author(s) -
Campbell Jacob B,
Harrison Jon F
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.760.16
Subject(s) - hypoxia (environmental) , anoxic waters , biology , larva , anaerobic exercise , glycogen , physiology , carbohydrate metabolism , zoology , ecology , oxygen , endocrinology , chemistry , organic chemistry
Anoxia or severe hypoxia is a fundamental component of pathologies associated with heart disease, stroke and many other human pathologies; yet we still lack a fundamental understanding of how anoxia/severe hypoxia kills and the mechanisms responsible for the wide variation in anoxia tolerance across animals. Drosophila larvae feed on the yeasts of rotting fruits in a semi liquid environment, and as a consequence, the larvae regularly experience episodes of hypoxia/anoxia whereas adults live in air and are likely to experience hypoxia on rare occasions. Perhaps surprisingly, larvae are much less tolerant of anoxia than adults; nearly 100% of adults survive up to 4 hours of anoxia while less than 50% of third in star larvae survive anoxic bouts greater than 90 minutes. We used biochemical and physiological methods to assess stage‐related variation in the ability to match ATP supply and demand, and in addition, we conducted a genome‐wide association study to find and then verify candidate genes responsible for variation in anoxia survival within populations of larvae and adults. Anoxia induced strong decreases in glycogen levels in both larvae and adults; however, both stages also showed strong increases in free glucose indicating that carbohydrate depletion is likely not a cause of death. Both larvae and adults accumulated lactate, but larvae did so at a higher rate during the first hour of anoxic exposure which suggests that high locomotion of larvae during initial exposure to hypoxia requires high rates of anaerobic metabolism that may be functionally linked to mortality. Preliminary measures of ATP show that ATP declines to near zero at the first measured time points—2 hours for adults and 30 minutes for larvae. Survival of a 1 hour anoxia exposure was highly repeatable but varied greatly across 178 lines from the Drosophila Genetics Reference Panel ranging from 25–95%. Thirty‐two SNPs and 23 genes were associated with the variation in survival across lines, all with P values less than 0.00001. Gene ontology enrichment analysis implicates differential genes in classes involved in vertebrate angiogenesis, cell proliferation, membrane/cytoskeletal remodeling, and fatty acid metabolism associated with differential survival across lines. Several of the identified genes linked to survival across the DGRP lines have human orthologs that have been linked to oxygen‐mediated cancer pathways and Alzheimer's progression in humans. Support or Funding Information This research was supported by NSF IOS 1256745.