Dataset Information

Cross-Kingdom Analysis of Diversity, Evolutionary History, and Site Selection within the Eukaryotic Macrophage Migration Inhibitory Factor Superfamily.

ABSTRACT: Macrophage migration inhibitory factors (MIF) are multifunctional proteins regulating major processes in mammals, including activation of innate immune responses. MIF proteins also play a role in innate immunity of invertebrate organisms or serve as virulence factors in parasitic organisms, raising the question of their evolutionary history. We performed a broad survey of MIF presence or absence and evolutionary relationships across 803 species of plants, fungi, protists, and animals, and explored a potential relation with the taxonomic status, the ecology, and the lifestyle of individual species. We show that MIF evolutionary history in eukaryotes is complex, involving probable ancestral duplications, multiple gene losses and recent clade-specific re-duplications. Intriguingly, MIFs seem to be essential and highly conserved with many sites under purifying selection in some kingdoms (e.g., plants), while in other kingdoms they appear more dispensable (e.g., in fungi) or present in several diverged variants (e.g., insects, nematodes), suggesting potential neofunctionalizations within the protein superfamily.

SUBMITTER: Michelet C

PROVIDER: S-EPMC6826473 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

Cross-Kingdom Analysis of Diversity, Evolutionary History, and Site Selection within the Eukaryotic Macrophage Migration Inhibitory Factor Superfamily.

Michelet Claire C Danchin Etienne G J EGJ Jaouannet Maelle M Bernhagen Jürgen J Panstruga Ralph R Kogel Karl-Heinz KH Keller Harald H Coustau Christine C

Genes 20190924 10

Macrophage migration inhibitory factors (MIF) are multifunctional proteins regulating major processes in mammals, including activation of innate immune responses. MIF proteins also play a role in innate immunity of invertebrate organisms or serve as virulence factors in parasitic organisms, raising the question of their evolutionary history. We performed a broad survey of MIF presence or absence and evolutionary relationships across 803 species of plants, fungi, protists, and animals, and explor ...[more]

PMID: 31554205

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Project description:Alcohol use disorder (AUD) is a primary, chronic and relapsing disease of brain reward, motivation and memory, which is associated with several comorbidities, including major depression and post-traumatic stress disorder. It has been revealed that Ibudilast (IBUD), a dual inhibitor of phosphodiesterase-4 and -10 and of macrophage migration inhibitory factor (MIF), exerts beneficial effects on AUD in rodent models and human patients. Therefore, IBUD has attracted increasing interest, with research focusing on the elucidation of the pathogenic role of MIF and its homologue, D-dopachrome tautomerase (DDT), in the pathogenesis and maintenance of AUD. By using DNA microarray analysis, the current study performed a transcriptomic expression analysis of MIF, DDT and their co-receptors, including CD74, C-X-C chemokine receptor (CXCR)2, CXCR4 and CXCR7 in patients with AUD. The results revealed that the transcriptomic levels of MIF, DDT and their receptors were superimposable in the prefrontal cortex of rodents and patients with AUD and human patients. Furthermore, peripheral blood cells from heavy drinkers exhibited a moderate increase in MIF and DDT levels, both at the baseline and following exposure to alcohol-associated cues, based on individual situations that included alcohol-related stimuli resulting in subsequent alcohol use (buying alcohol and being at a bar, watching others drink alcohol). Considering the overlapping effects of MIF and DDT, the inverse Fisher's χ2 test was performed on unadjusted P-values to evaluate the combined effect of MIF and DDT. The results revealed a significant increase in these cytokines in heavy drinkers compared with controls (moderate drinkers). To the best of our knowledge, the present study demonstrated for the first time that MIF and DDT expression was upregulated in the blood of patients with AUD. These results therefore warrant further study to evaluate the role of MIF and DDT in the development and maintenance of AUD, to evaluate their use as biomarkers to predict the psychotherapeutic and pharmacological response of patients with AUD and for use as therapeutic targets.

Project description:The emergence of multigene families has been hypothesized as a major contributor to the evolution of complex traits and speciation. To help understand how such multigene families arose and diverged during plant evolution, we examined the phylogenetic relationships of F-Box (FBX) genes, one of the largest and most polymorphic superfamilies known in the plant kingdom. FBX proteins comprise the target recognition subunit of SCF-type ubiquitin-protein ligases, where they individually recruit specific substrates for ubiquitylation. Through the extensive analysis of 10,811 FBX loci from 18 plant species, ranging from the alga Chlamydomonas reinhardtii to numerous monocots and eudicots, we discovered strikingly diverse evolutionary histories. The number of FBX loci varies widely and appears independent of the growth habit and life cycle of land plants, with a little as 198 predicted for Carica papaya to as many as 1350 predicted for Arabidopsis lyrata. This number differs substantially even among closely related species, with evidence for extensive gains/losses. Despite this extraordinary inter-species variation, one subset of FBX genes was conserved among most species examined. Together with evidence of strong purifying selection and expression, the ligases synthesized from these conserved loci likely direct essential ubiquitylation events. Another subset was much more lineage specific, showed more relaxed purifying selection, and was enriched in loci with little or no evidence of expression, suggesting that they either control more limited, species-specific processes or arose from genomic drift and thus may provide reservoirs for evolutionary innovation. Numerous FBX loci were also predicted to be pseudogenes with their numbers tightly correlated with the total number of FBX genes in each species. Taken together, it appears that the FBX superfamily has independently undergone substantial birth/death in many plant lineages, with its size and rapid evolution potentially reflecting a central role for ubiquitylation in driving plant fitness.

Dataset Information

Cross-Kingdom Analysis of Diversity, Evolutionary History, and Site Selection within the Eukaryotic Macrophage Migration Inhibitory Factor Superfamily.

Publications

Cross-Kingdom Analysis of Diversity, Evolutionary History, and Site Selection within the Eukaryotic Macrophage Migration Inhibitory Factor Superfamily.

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