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Table 1.

Milestones in the acquisition of coordinate regulation of glycolytic enzyme genes by hypoxia

BYAPeriodOrganismRegulatorElementResponse
3.5 Archea1 Therm/S-Bacteria Carbohydrate cre/ccpA Global 
   Sulfur/Phosphate Global 
1.0 Vendian2 Fungi/Yeast Carbohydrate GCR1 Key enzymes 
   Hypoxia/Anoxia LORE: ACTCAACAA Key enzymes 
   Hypoxia (Repression) ROX-1: CCATTGTTCTC  
    HAP1: CGGN6CGG  
0.6 Devonian3 Higher plants Hypoxia/anoxia (Other stress) HREs TGGTTT GC(G/C)CC ACGTG Key enzymes 
0.4 Silurian4 Fish/Insects Hypoxia HRE/HIF-1α ACGTG Coordinate 
Cambrian Animals/Mammals Hypoxia HRE/HIF-1/Ap-1/Sp1 ACGTG TGATTC GC(G/C)GC Coordinate 
BYAPeriodOrganismRegulatorElementResponse
3.5 Archea1 Therm/S-Bacteria Carbohydrate cre/ccpA Global 
   Sulfur/Phosphate Global 
1.0 Vendian2 Fungi/Yeast Carbohydrate GCR1 Key enzymes 
   Hypoxia/Anoxia LORE: ACTCAACAA Key enzymes 
   Hypoxia (Repression) ROX-1: CCATTGTTCTC  
    HAP1: CGGN6CGG  
0.6 Devonian3 Higher plants Hypoxia/anoxia (Other stress) HREs TGGTTT GC(G/C)CC ACGTG Key enzymes 
0.4 Silurian4 Fish/Insects Hypoxia HRE/HIF-1α ACGTG Coordinate 
Cambrian Animals/Mammals Hypoxia HRE/HIF-1/Ap-1/Sp1 ACGTG TGATTC GC(G/C)GC Coordinate 

BYA is billion years ago.

1

Strictly anaerobic organisms in the Archean period developed sophisticated pathways for substrate regulation of bioenergetic enzyme gene expression,including regulation by sulfur and phosphorus.

2

The Vendian organisms are representative of the transition to oxidative metabolism and include the first examples of oxygen-regulated gene switching.

3

The Devonian period includes the first example of anaerobic response elements in glycolytic enzyme genes, including regulation by the sequence element ACGT that binds factor HIF-1α in higher animals (but not plants).

4

Contemporaty pathways that coordinate glycolytic enzyme gene expression in response to hypoxia probably originated in the Silurian period, coincident with multicellularity and metabolic compartmentation.

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