The Relationship between Environmental Dioxygen and Iron-Sulfur Proteins Explored at the Genome Level

Abstract

About 2 billion years ago, the atmosphere of the Earth experienced a great change due to the buildup of dioxygen produced by photosynthetic organisms. This transition caused a reduction of iron bioavailability and at the same time exposed living organisms to the threat of oxidative stress. Iron-sulfur (Fe-S) clusters require iron ions for their biosynthesis and are labile if exposed to reactive oxygen species. To assess how the above transition influenced the usage of Fe-S clusters by organisms, we compared the distribution of the Fe-S proteins encoded by the genomes of more than 400 prokaryotic organisms as a function of their dioxygen requirements. Aerobic organisms use less Fe-S proteins than the majority of anaerobic organisms with a similar genome size. Furthermore, aerobes have evolved specific Fe-S proteins that bind the less iron-demanding and more chemically stable Fe2S2 clusters while reducing the number of Fe4S4-binding proteins in their genomes. However, there is a shared core of Fe-S protein families composed mainly by Fe4S4-binding proteins. Members of these families are present also in humans. The distribution of human Fe-S proteins within cell compartments shows that mitochondrial proteins are inherited from prokaryotic proteins of aerobes, whereas nuclear and cytoplasmic Fe-S proteins are inherited from anaerobic organisms.

Fig 1. Dependence of the number of Fe-S proteins and Fe-S families on the genome size of the organisms.

A) Number of putative Fe-S proteins as a function of the genome size in aerotolerant anaerobes (orange crosses), obligate anaerobes (red squares), aerobes (light blue triangles) and obligate aerobes (royal blue circles). The black line represent the threshold (3% of the genome content) used to separate LC aerotolerant anaerobes from HC aerotolerant anaerobes. B) Average number of distinct Fe-S families as a function of the genome size in HC aerotolerant anaerobes (orange crosses), obligate anaerobes (red squares), aerobes (light blue triangles) and obligate aerobes (royal blue circles).

Fig 2. Frequently occurring (i.e. present in at least 30% organisms) families of Fe-S proteins in aerobes and HC anaerobes.

(A): Venn diagram showing the distribution of the 116 frequently occurring Fe-S families within aerobes and HC anaerobes. (B), (C), and (D): Pie charts showing the types of Fe-S cluster (blue: Fe₂S₂; orange: Fe₄S₄; green: Fe₃S₄; yellow: two or more of Fe₂S₂-Fe₄S₄-Fe₃S₄; red: FeCys₄; grey: unknown type) associated with families conserved in aerobes (B), in anaerobes (D), and in both (C). (E), (F), and (G): histograms showing the number of families associated with specific functional processes in aerobes (E), in anaerobes (G), and in both (F). More than one functional process may be associated with a family. Unknown functional processes are excluded from the count.

Fig 3. The occurrence of (A) and the Fe-S cluster type (B) in the Fe-S families of humans, aerobes and HC anaerobes.

In panel A, human Fe-S families that did not map to any prokaryotic family of Fig 2 are classified as “Human”. Panel B displays the average fraction of proteins binding at least one cluster of the Fe₂S₂ or of the Fe₄S₄ type.

Fig 4. Distribution of the frequently occurring Fe-S families of aerobes and HC anaerobes within facultative anaerobes (A) and LC aerotolerant anaerobes (B).

The black part of the column indicates the occurrence of the families of the three groups defined in Fig 2 within facultative anaerobes (A) and LC aerotolerant anaerobes (B). The grey part of the column indicates the absent families. The last columns correspond to Fe-S families unique to facultative anaerobes (A) and LC aerotolerant anaerobes (B), i.e. not mapping to any family in the Venn diagram of Fig 2.