Bird evolution by insulin resistance

Abstract

Drift of oxygen concentrations in the atmosphere was one of the main drivers of the evolution of vertebrates. The drop in oxygen concentrations at the Permian-Triassic (PT) boundary may have been the biggest challenge to vertebrates. This hypoxic condition forced theropods to lose certain genes to maximize their efficiency of oxygen usage. Recent studies show that omentin and insulin-sensitive glucose transporter 4 (GLUT4) are missing in the bird genome. Since these gene products play essential roles in maintaining insulin sensitivity, this loss forced theropods to become insulin resistant. Insulin resistance may have been the key to allowing theropods to become hyperathletic under hypoxic conditions and to outcompete mammals during the Triassic period. A second challenge was the gradual increase in oxygen concentrations during the late Jurassic, Cretaceous, and Tertiary periods when reactive oxygen species (ROS) leakage from mitochondria became a problem. Since the simplest solution was the expansion of body size, some theropods became bigger to reduce ROS leakage per volume. Another solution was the development of a constitutively active countermeasure against ROS. A recent study shows that Neoaves have constitutively active nuclear factor erythroid 2-related factor 2 (NRF2) due to deletion of the C-terminal part of the KEAP1 protein, thus allowing Neoaves to express antioxidant enzymes to overcome ROS leakage.

The ecology of cancer prevalence across species: Cancer prevalence is highest in desert species and high trophic levels

“…Additionally, higher metabolic rates are characteristic of higher trophic levels 42,106,107 . Still, birds have higher metabolic rates than mammals [20][21][22][23][24] , and lower cancer prevalence than mammals [25][26][27][28] .…”

“…Still, a recent study suggests that high metabolic rates might be cancer protective 19 . Birds are known to have higher metabolic rates than mammals [20][21][22][23][24] , and lower cancer prevalence than mammals [25][26][27][28] .…”

SLC3A2 N-glycosylation and alternate evolutionary trajectories for amino acid metabolism

“…Mgat6, Uniprot: Q9DGD1) acquired a novel activity, adding a fifth N-glycan branch expected to increase affinities for galectins (11, 109). Neoaves have streamlined other genes associated with glucose homeostasis, notably losses of insulin-inducible glucose transporter (SLC2A4), glucokinase regulatory protein (GCKR), S/T-protein kinase (AKT2), fibroblast growth factor 21 (FGF21) (98), and an evolved resistance of proteins to glycation (126). Perhaps as a consequence, the Advanced Glycation End product-specific Receptor (AGER) is absent in Neoaves, which in mammals, sends AGE-damaged extracellular matrix proteins to intracellular degradation, as well as signaling that opposes ox-stress (127).…”

“…Phylogenetic analysis of modern birds (Neoaves) suggests a massive protein-coding sequence convergence, and incomplete lineage sorting during rapid radiation after the Cretaceous-Paleogene mass extinction event ~66 MYA (97). Selective pressures drove changes in physiology and metabolism and a surprising ~25% reduction in genome size, discarding many genes and duplicating a few others (98)(99)(100). Evolution generally makes use of mutations in existing genes, and less frequently gene inactivation and losses occur when their contribution to fitness wanes.…”

“…Central metabolism and compartmentalized: Further manual analysis using UniProt and sequence alignment provided insight on additional streamlining of paralogues, that are often compartmentalized at the cellular and organ levels. Muscle glycogen synthesis (GYS1) is absent, presumably replaced by higher levels of circulating glucose (98) and by mobilization of fatty acids and ketones during flight. Carnitine O-palmitoyltransferase 1a (CPT1A, kidney, heart, liver) is present, and CPT1B/C (muscle, brain) are absent, consistent with liver as the major supplier of ketones to other tissues (Fig.…”