The convoluted history of haem biosynthesis

Abstract

The capacity of haem to transfer electrons, bind diatomic gases, and catalyse various biochemical reactions makes it one of the essential biomolecules on Earth and one that was likely used by the earliest forms of cellular life. Since the description of haem biosynthesis, our understanding of this multi‐step pathway has been almost exclusively derived from a handful of model organisms from narrow taxonomic contexts. Recent advances in genome sequencing and functional studies of diverse and previously neglected groups have led to discoveries of alternative routes of haem biosynthesis that deviate from the ‘classical’ pathway. In this review, we take an evolutionarily broad approach to illuminate the remarkable diversity and adaptability of haem synthesis, from prokaryotes to eukaryotes, showing the range of strategies that organisms employ to obtain and utilise haem. In particular, the complex evolutionary histories of eukaryotes that involve multiple endosymbioses and horizontal gene transfers are reflected in the mosaic origin of numerous metabolic pathways with haem biosynthesis being a striking case. We show how different evolutionary trajectories and distinct life strategies resulted in pronounced tensions and differences in the spatial organisation of the haem biosynthesis pathway, in some cases leading to a complete loss of a haem‐synthesis capacity and, rarely, even loss of a requirement for haem altogether.

Discovery of Early-Branching Wolbachia Reveals Functional Enrichment on Horizontally Transferred Genes

“…Together, these findings are consistent with the ‘iron hypothesis’ for Wolbachia which posits that heme biosynthesis and iron homeostasis may be central to the maintenance of Wolbachia ( Foster et al, 2005 ; Wu et al, 2009 ; Darby et al, 2012 ; Gill et al, 2014 ; Luck et al, 2014 ; Brown et al, 2016 ). Nematodes are exceptional among animals in having lost the ability to synthesize heme early in their evolution as bacterivores ( Rao et al, 2005 ; Slatko et al, 2010 ; Elsworth et al, 2011 ; Kořený et al, 2021 ). Most nematodes, as bacterivores, can extract ample heme from their diets.…”

“…However, one possibility is that these PPN Wolbachia strains may generate excess protoporphyrin as a toxin. The observation that Wolbachia w Ppe is localized adjacent to the esophageal glands ( Brown et al, 2016 ) could indicate a role for these Wolbachia in producing protoporphyrin destined for nematode secretions during migratory endoparasitic feeding, which may trigger programmed cell death in plant roots by disrupting mitochondrial membranes ( Kořený et al, 2021 ), facilitating nematode feeding.…”

Heme-deficient metabolism and impaired cellular differentiation as an evolutionary trade-off for human infectivity in Trypanosoma brucei gambiense

“…Here we show that in T. b. gambiense, this receptor also effectively prevents the import of heme with consequences for the heme-requiring cellular processes. While this would be lethal for a typical aerobic eukaryote that depends on external heme, trypanosomatids such as the abovementioned Phytomonas have a unique capacity to tolerate its complete deficiency (46). Changes in T. b. gambiense HpHbR seem to have far-reaching consequences.…”

Heme-deficient metabolism and impaired cellular differentiation as an evolutionary trade-off for human infectivity in Trypanosoma brucei gambiense

“…The heme group is needed to sustain the life of almost all eukaryotic organisms analyzed so far 45 , 46 . Nevertheless, it has remained unclear whether trypanosomes still require heme while residing in the mammalian host.…”

“…Here we show that in T. b. gambiense , this receptor also effectively prevents the import of heme with consequences for the heme-requiring cellular processes. While this would be lethal for a typical aerobic eukaryote that depends on external heme, trypanosomatids such as the abovementioned Phytomonas have a unique capacity to tolerate its complete deficiency 46 .…”