The evolution of the cytochrome c6 family of photosynthetic electron transfer proteins

During photosynthesis, electrons are transferred between the cytochrome b6f complex and photosystem I. This is carried out by the protein plastocyanin in plant chloroplasts. In contrast, electron transfer can be carried out by either plastocyanin or cytochrome c6 in many cyanobacteria and eukaryotic algal species. There are three further cytochrome c6 homologues: cytochrome c6A in plants and green algae, and cytochromes c6B and c6C in cyanobacteria. The function of these proteins is unknown. Here, we present a comprehensive analysis of the evolutionary relationship between the members of the cytochrome c6 family in photosynthetic organisms. Our phylogenetic analyses show that cytochrome c6B and cytochrome c6C are likely to be orthologues that arose from a duplication of cytochrome c6, but that there is no evidence for separate origins for cytochrome c6B and c6C. We therefore propose re-naming cytochrome c6C as cytochrome c6B. We show that cytochrome c6A is likely to have arisen from cytochrome c6B rather than by an independent duplication of cytochrome c6, and present evidence for an independent origin of a protein with some of the features of cytochrome c6A in peridinin dinoflagellates. We conclude with a new comprehensive model of the evolution of the cytochrome c6 family which is an integral part of understanding the function of the enigmatic cytochrome c6 homologues.

Rapid Evolution of HERC6 and Duplication of a Chimeric HERC5/6 Gene in Rodents and Bats Suggest an Overlooked Role of HERCs in Mammalian Immunity

Studying the evolutionary diversification of mammalian antiviral defenses is of main importance to better understand our innate immune repertoire. The small HERC proteins are part of a multigene family, including HERC5 and HERC6, which have probably diversified through complex evolutionary history in mammals. Here, we performed mammalian-wide phylogenetic and genomic analyses of HERC5 and HERC6, using 83 orthologous sequences from bats, rodents, primates, artiodactyls, and carnivores—the top five representative groups of mammalian evolution. We found that HERC5 has been under weak and differential positive selection in mammals, with only primate HERC5 showing evidences of pathogen-driven selection. In contrast, HERC6 has been under strong and recurrent adaptive evolution in mammals, suggesting past and widespread genetic arms-races with viral pathogens. Importantly, the rapid evolution of mammalian HERC6 spacer domain suggests that it might be a host-pathogen interface, targeting viral proteins and/or being the target of virus antagonists. Finally, we identified a HERC5/6 chimeric gene that arose from independent duplication in rodent and bat lineages and encodes for a conserved HERC5 N-terminal domain and divergent HERC6 spacer and HECT domains. This duplicated chimeric gene highlights adaptations that potentially contribute to rodent and bat immunity. Our findings open new research avenues on the functions of HERC6 and HERC5/6 in mammals, and on their implication in antiviral innate immunity.

Rapid evolution of mammalian HERC6 and independent duplication of a chimeric HERC5/6 gene in rodents and bats suggest an overlooked role of HERCs in antiviral innate immunity

The antiviral innate immunity in mammals has evolved very rapidly in response to pathogen selective pressure. Studying the evolutionary diversification of mammalian antiviral defenses is of main importance to better understand our innate immune repertoire. The small HERC proteins are part of a multigene family including interferon-inducible antiviral effectors. Notably, HERC5 inhibits divergent viruses through the conjugation of ISG15 to diverse proteins-termed as ISGylation. Though HERC6 is the most closely-related protein of HERC5, it lacks the ISGylation function in humans. Interestingly, HERC6 is the main E3-ligase of ISG15 in mice, suggesting adaptive changes in HERC6 with implications in the innate immunity. Therefore, HERC5 and HERC6 have probably diversified through complex evolutionary history in mammals, and such characterization would require an extensive survey of mammalian evolution. Here, we performed mammalian-wide and lineage-specific phylogenetic and genomic analyses of HERC5 and HERC6. We used 83 orthologous sequences from bats, rodents, primates, artiodactyls and carnivores – the top five representative groups of mammalian evolution and the main hosts of viral diversity. We found that mammalian HERC5 has been under weak and differential positive selection in mammals, with only primate HERC5 showing evidences of pathogen-driven selection. In contrast, HERC6 has been under strong and recurrent adaptive evolution in mammals, suggesting past genetic arms-races with viral pathogens. Importantly, we found accelerated evolution in the HERC6 spacer domain, suggesting that it might be a pathogen-mammal interface, targeting a viral protein and/or being the target of virus antagonists. Finally, we identified a HERC5/6 chimeric gene that arose from independent duplication in rodent and bat lineages and encodes for a conserved HERC5 N-terminal domain and divergent HERC6 spacer and HECT domains. This duplicated chimeric gene highlights adaptations that potentially contribute to rodent and bat antiviral innate immunity. Altogether, we found major genetic innovations in mammalian HERC5 and HERC6. Our findings open new research avenues on the functions of HERC6 and HERC5/6 in mammals, and on their implication in antiviral innate immunity.

Recurrent Sequence Evolution After Independent Gene Duplication

Background Convergent and parallel evolution provide unique insights into the mechanisms of natural selection. Some of the most striking convergent and parallel (collectively recurrent ) amino acid substitutions in proteins are adaptive, but there are also many that are selectively neutral. Genome-wide assessment of recurrent substitutions has only been performed for orthologs. These studies have revealed that the pervasiveness of recurrent substitutions is for a large part explained by purifying selection. At any position in a protein, only a subset of amino acids is allowed, increasing the chance of the same substitution happening in different lineages. ResultsWe developed a framework that detects patterns of recurrent differentiation in paralogs across 90 divergent eukaryotic genomes. A skew in recurrent substitutions serves as a proxy for a recurrent trend in function. We find remarkable examples of recurrent sequence evolution after independent duplication, in some cases involving more than ten different lineages where duplicates show a similar differentiation. We reveal the implicated functional patterns for the gene families Hint1/Hint2, Sco1/Sco2 and vma11/vma3. ConclusionsThe presented methodology provides a means to study the biochemical underpinning of functional differentiation between paralogs. For instance, two abundantly repeated substitutions are identified between independently derived Sco1 and Sco2 paralogs. Such identified substitutions allow direct experimental testing of the biological role of these residues for the repeated functional differentiation. The present study uncovers a diverse set of families with recurrent sequence evolution and reveals trends in the functional and evolutionary trajectories of this hitherto understudied phenomenon.

Phylogenetic evidence for independent origins of GDF1 and GDF3 genes in amphibians and mammals

Growth differentiation factors 1 (GDF1) and 3 (GDF3) are members of the transforming growth factor superfamily (TGF-β) that is involved in fundamental early-developmental processes that are conserved across vertebrates. The evolutionary history of these genes is still under debate due to ambiguous definitions of homologous relationships among vertebrates. Thus, the goal of this study was to unravel the evolution of the GDF1 and GDF3 genes of vertebrates, emphasizing the understanding of homologous relationships and their evolutionary origin. Surprisingly, our results revealed that the GDF1 and GDF3 genes found in amphibians and mammals are the products of independent duplication events of an ancestral gene in the ancestor of each of these lineages. The main implication of this result is that the GDF1 and GDF3 genes of amphibians and mammals are not 1:1 orthologs. In other words, genes that participate in fundamental processes during early development have been reinvented two independent times during the evolutionary history of tetrapods.

Evidence for parallel evolution of a gene involved in the regulation of spermatogenesis

PHD finger protein 7 ( Phf7 ) is a male germline specific gene in Drosophila melanogaster that can trigger the male germline sexual fate and regulate spermatogenesis, and its human homologue can rescue fecundity defects in male flies lacking this gene. These findings prompted us to investigate conservation of reproductive strategies through studying the evolutionary origin of this gene. We find that Phf7 is present only in select species including mammals and some insects, whereas the closely related G2/M-phase specific E3 ubiquitin protein ligase ( G2e3 ) is in the genome of most metazoans. Interestingly, phylogenetic analyses showed that vertebrate and insect Phf7 genes did not evolve from a common Phf7 ancestor but rather through independent duplication events from an ancestral G2e3 . This is an example of parallel evolution in which a male germline factor evolved at least twice from a pre-existing template to develop new regulatory mechanisms of spermatogenesis.

Concurrent duplication of the Cid and Cenp-C genes in the Drosophila subgenus with signatures of subfunctionalization and male germline-biased expression

Despite their essential role in the process of chromosome segregation in eukaryotes, kinetochore proteins are highly diverse across species, being lost, duplicated, created, or diversified during evolution. Based on comparative genomics, the duplication of the inner kinetochore proteins CenH3 and Cenp-C, which are interdependent in their roles of stablishing centromere identity and function, can be said to be rare in animals. Surprisingly, the Drosophila CenH3 homolog Cid underwent four independent duplication events during evolution. Particularly interesting are the highly diverged and subfunctionalized Cid1 and Cid5 paralogs of the Drosophila subgenus, which show that over one thousand Drosophila species may encode two Cid genes, making those with a single copy a minority. Given that CenH3 and Cenp-C likely co-evolve as a functional unit, we investigated the molecular evolution of Cenp-C in species of Drosophila. We report yet another Cid duplication within the Drosophila subgenus and show that not only Cid, but also Cenp-C is duplicated in the entire subgenus. The Cenp-C paralogs, which we named Cenp-C1 and Cenp-C2, are highly divergent. The retention of key motifs involved in centromere localization and function by both Cenp-C1 and Cenp-C2 makes neofunctionalization unlikely. In contrast, the alternate conservation of some functional motifs between the proteins is indicative of subfunctionalization. Interestingly, both Cid5 and Cenp-C2 are male germline-biased and evolved adaptively. Our findings point towards a specific inner kinetochore composition in a specific context (i.e., spermatogenesis), which could prove valuable for the understanding of how the extensive kinetochore diversity is related to essential cellular functions.

SCPP Gene Evolution and the Dental Mineralization Continuum

Many genes critical to vertebrate skeletal mineralization are members of the secretory calcium-binding phosphoprotein (SCPP) gene family, which has evolved by gene duplication from a single ancestral gene. In humans, mutations in some of these SCPP genes have been associated with various diseases related to dentin or enamel hypoplasia. Recently, systematic searches for SCPP genes of various species have allowed us to investigate the history of phylogenetically variable dental tissues as a whole. One important conclusion is that not all disease-associated SCPP genes are present in tetrapods, and teleost fish probably have none, even in toothed species, having acquired their complement of SCPP genes through an independent duplication history. Here, we review comparative analyses of mineralized dental tissues, with particular emphasis on the use of SCPPs, within and between tetrapods and teleosts. Current knowledge suggests a close relationship among bone, dentin, teleost fish enameloid (enamel-like hard tissue), and tetrapod enamel. These tissues thus form a mineralized-tissue continuum. Contemporary dental tissues have evolved from an ancestral continuum through lineage-specific modifications.