Revisiting the growth rate hypothesis: Towards a holistic stoichiometric understanding of growth

Abstract

The growth rate hypothesis (GRH) posits that variation in organismal stoichiometry (C:P and N:P ratios) is driven by growth‐dependent allocation of P to ribosomal RNA. The GRH has found broad but not uniform support in studies across diverse biota and habitats. We synthesise information on how and why the tripartite growth‐RNA‐P relationship predicted by the GRH may be uncoupled and outline paths for both theoretical and empirical work needed to broaden the working domain of the GRH. We found strong support for growth to RNA (r2 = 0.59) and RNA‐P to P (r2 = 0.63) relationships across taxa, but growth to P relationships were relatively weaker (r2 = 0.09). Together, the GRH was supported in ~50% of studies. Mechanisms behind GRH uncoupling were diverse but could generally be attributed to physiological (P accumulation in non‐RNA pools, inactive ribosomes, translation elongation rates and protein turnover rates), ecological (limitation by resources other than P), and evolutionary (adaptation to different nutrient supply regimes) causes. These factors should be accounted for in empirical tests of the GRH and formalised mathematically to facilitate a predictive understanding of growth.

Adaptation to a limiting element involves mitigation of multiple elemental imbalances

“…For example, direct selection for rapid growth would enable us to test predictions arising from the growth rate hypothesis (e.g. [58]). Regardless, the main inferences arising from observations on NUEs across the ionome is that adaptation to limiting supply of an element often involves shifts in the use of not only the limiting element (as posited by the nutrient sparing hypothesis), but also correlated shifts in multiple other elements (table 1).…”

Link between Energy Investment in Biosynthesis and Proteostasis: Testing the Cost–Quality Hypothesis in Insects

“…The results in Figure 8 echo the recent development in the field of biological stoichiometry. It has long been hypothesized (Growth Rate Hypothesis) that fast-growing organisms need relatively more phosphorus-rich RNA to support rapid rates of protein synthesis, and therefore, growth rate is positively associated with RNA content [ 59 , 60 , 77 , 78 ]. While the Growth Rate Hypothesis (GRH) has gained support from observations of a wide range of organisms, the positive association between growth rate and RNA content is often decoupled in many organisms [ 59 , 60 ].…”

“…It has long been hypothesized (Growth Rate Hypothesis) that fast-growing organisms need relatively more phosphorus-rich RNA to support rapid rates of protein synthesis, and therefore, growth rate is positively associated with RNA content [ 59 , 60 , 77 , 78 ]. While the Growth Rate Hypothesis (GRH) has gained support from observations of a wide range of organisms, the positive association between growth rate and RNA content is often decoupled in many organisms [ 59 , 60 ]. Among other reasons, recent studies suggest [ 59 , 60 ] that the decoupling is due to GRH’s assumption of a constant protein retention, i.e., a fixed fraction of synthesized protein accumulates in the cell, contributing to growth, and that “high rates of protein turnover keep proteins from accumulating in cells, thus decoupling growth from RNA.” Our results, in agreement with this explanation, paint a coherent picture: Compared to the caterpillar, the higher proteasome activities ( Figure 7 ) in the cockroach lead to a higher protein turnover rate.…”

“…While the Growth Rate Hypothesis (GRH) has gained support from observations of a wide range of organisms, the positive association between growth rate and RNA content is often decoupled in many organisms [ 59 , 60 ]. Among other reasons, recent studies suggest [ 59 , 60 ] that the decoupling is due to GRH’s assumption of a constant protein retention, i.e., a fixed fraction of synthesized protein accumulates in the cell, contributing to growth, and that “high rates of protein turnover keep proteins from accumulating in cells, thus decoupling growth from RNA.” Our results, in agreement with this explanation, paint a coherent picture: Compared to the caterpillar, the higher proteasome activities ( Figure 7 ) in the cockroach lead to a higher protein turnover rate. This enables proteostasis and cellular resistance to oxidative stress ( Figure 3 , Figure 4 , Figure 5 and Figure 6 ) and a higher RNA/growth ratio ( Figure 8 ).…”

“…Finally, species with higher E m values spend a large percentage of protein on replacing the newly synthesized proteins that have errors. Thus, for a given amount of RNA, the high- E m species deposit a smaller fraction of newly synthesized protein as new bio-tissue than the low- E m species, leading to a higher RNA-to-growth ratio (RNA:growth) [ 59 , 60 ]. We measured the RNA content and biomass growth rate of the midgut tissue of these species to test this prediction.…”