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. Author manuscript; available in PMC: 2015 Feb 25.
Published in final edited form as: Trends Dev Biol. 2014;8:17–37.

Fig. 3.

Fig. 3

Alternating extrinsic and intrinsic selection pressures for the genes of lung phylogeny and ontogeny. The effects of the extrinsic factors (salinity, land nutrients, and oxygen on the x-axis) on genes that determine the phylogeny and ontogeny of the mammalian lung alternate sequentially with the intrinsic genetic factors (y-axis), highlighted by the squares and circles, respectively. Steps 1–11 appear in the sequence they appear during phylogeny and ontogeny: [1] AMPs; [2] VDR; [3] type IV collagen; [4] GR; [5] 11β HSD; [6] βAR; [7] ADRP; [8] leptin; [9] leptin receptor; [10] PTHrP; and [11] SP-B. Steps 12–17 represent the pleiotropic effects of leptin on the EGF in oval signaling pathways integrating steps 1–6, 10, and 11. Steps 18–20 are major geologic epochs that have “driven” intrinsic lung evolution.