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Oxygen‐Directed Laboratory Evolution and Conserved Mechanisms Underlying Hypoxia Tolerance
Author(s) -
Zhou Dan,
Iranmehr Arya,
Zhao Helen,
Stobdan Tsering,
Bafna Vineet,
Haddad Gabriel G.
Publication year - 2020
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.2020.34.s1.09902
Subject(s) - biology , drosophila melanogaster , adaptation (eye) , experimental evolution , evolutionary biology , genome , genetics , gene , negative selection , selection (genetic algorithm) , neuroscience , artificial intelligence , computer science
Oxygen is essential for metazoan life on earth. In this work, we have taken advantage of Drosophila melanogaster as a genetic model system to dissect mechanisms of genomic adaptation to extreme oxygen conditions. We conducted a ~15‐year laboratory evolution experiment over >290 generations by chronically exposing multiple fly populations to normal, decreasing, or increasing O 2 levels to determine the effect of selection pressure on their genomes, and to understand the mechanisms of adaptation to O 2 imbalance. We have obtained Drosophila melanogaster populations and strains that can tolerate and perpetually survive environments containing extremely low (<4%) or high (>90%) level of O 2 , which are lethal for naïve controls. A time series of whole genome sequencing (WGS) analysis of multiple generations of the Low (L‐O 2 ) and high (H‐O 2 ) populations and normoxia control (N‐populations) demonstrated clear genomic changes along evolution between environments and generations. Furthermore, four genomic regions in the H‐O 2 populations and five genomic regions in the L‐O 2 populations were identified, which contain selection sweeps generated by selections with low or high oxygen condition. A total of 433 candidate genes and 215 candidate genes were identified in the selection sweeps in the L‐O 2 populations and H‐O 2 populations, respectively. This suggested a number of evolutionarily conserved mechanisms (e.g., the Notch signaling pathway) that may play a role in regulating adaptation to the extreme oxygen conditions. We believe that these mechanisms have a strong potential to be translated into humans and serve as novel targets for developing therapeutic strategies to prevent and treat hypoxia‐related diseases and oxidative stress‐induced injuries.