The anatomical and phylogenetic nature of the first mitochondrial ancestor

Abstract

Mitochondria are cell organelles that evolved by endosymbiosis. Even though the nature of the last mitochondrial common ancestor is well constrained, little is known about the nature of the first mitochondrial common ancestor. The goal of this thesis was to shed light on the anatomy and genealogy of the first mitochondrial ancestor.

Mitochondria compartmentalizes aerobic respiration inside membrane invaginations called cristae. The development of mitochondrial cristae involves the MICOS (Mitochondrial Contact Site and Cristae Organizing System) complex. I show that the core of MICOS, Mic60, is conserved across eukaryotes and was inherited from the alphaproteobacterial ancestor of mitochondria. Alphaproteobacterial Mic60 retains the same structure, domains and even a functionally critical amphipathic helix as eukaryotic Mic60. These observations revive the hypothesis that cristae might have evolved from intracytoplasmic membranes (ICMs). To experimentally test this hypothesis, I knocked out mic60 and orf52 (a gene immediately downstream of mic60) in two different ICM-developing alphaproteobacteria. Growth curves and transmission electron microscopy of these mutants show some differences relative to the wild type but do not provide a conclusive answer. However, in combination with additional experimental evidence provided by others, a stronger case is made for the conserved function of Mic60 in alphaproteobacteria supporting the hypothesis that cristae evolved from ICMs.

To better understand the specific evolutionary relationship between mitochondria and their closest relatives, the Alphaproteobacteria, I first inferred a robust phylogeny of the Alphaproteobacteria using a diverse set of strategies aimed at reducing systematic errors. I found that the parasitic Rickettsiales and Holosporales, previously thought to be most closely related to each other and to mitochondria, evolved independently from different ancestors. I then attempted to infer the phylogenetic placement of mitochondria by reconstructing novel alphaproteobacterial genomes from environmental metagenomes, including an expanded set of marker genes, and using improved methods for phylogenetic inference. Preliminary results suggest that mitochondria are sister to all the Alphaproteobacteria.

Together, these results suggest that the first mitochondrial ancestor was a free-living close relative of the modern Alphaproteobacteria that developed ICMs. This view is in opposition to a widely held view that mitochondria evolved from intracellular parasites.