Physiological Society, London, Mitochondrial meeting plenary lecture

London, United Kingdom

A bioenergetic basis for the three domains of life

The deep differences between the three domains of life are puzzling
and unexplained. Bacteria and archaea are almost indistinguishable
in their size and morphology, but are strikingly distinct in their
biochemical and metabolic properties, differing, for example, in the
genes responsible for glycolysis, cell membrane, cell wall, and even
DNA replication. In contrast, eukaryotes are chimeric, with most
of their informational genes deriving from archaea, and genes for
intermediary metabolism, as well as membranes, deriving from
bacteria. Eukaryotes apparently arose just once in 4 billion years of
evolution, around 2 billion years ago. Genetic divergence alone cannot
explain this evolutionary trajectory, as bacteria and archaea evolved
nothing resembling the morphological complexity of eukaryotes,
despite virtually unlimited exploration of genetic space. I will argue
that the differences between bacteria, archaea and eukaryotes are
not attributable to selection (or neutral evolution) operating on
populations of cells, but rather to the structural constraints imposed
by membrane bioenergetics. The divergence of bacteria and archaea
could have arisen from the dependence of LUCA, the last universal
common ancestor, on geologically sustained proton gradients in
alkaline hydrothermal vents at the origin of life. The constraints
imposed by membrane bioenergetics then prevented both prokaryotic
groups from becoming larger and more complex over 4 billion years of
evolution. These constraints were relaxed, at the origin of eukaryotes,
by a singular endosymbiosis between an archaeal host cell (probably
related to the Lokiarchaeota), and a proteobacterium, the ancestor
of mitochondria. This rare endosymbiosis restructured the topology
of eukaryotic genomes in relation bioenergetic membranes, with the loss of mitochondrial genes enabling the accumulation of genes and
gene families in the nucleus. In effect, eukaryotes have multi-bacterial
power without the huge genomic overheads of copying thousands of
full bacterial genomes. This extreme genomic asymmetry ultimately
gave eukaryotes 3-5 orders of magnitude more energy availability
per nuclear gene. The acquisition of mitochondria enabled a 15,000-
fold increase in maximal genome size, encompassing around a 5-10-
fold expansion in the number of protein-coding genes, coupled with
a 1000-10,000-fold expansion in gene expression. Many basal
eukaryotic traits, such as sex, probably evolved in the context of this
singular endosymbiosis between two prokaryotes.