Tsetse flies are the sole vectors of human African trypanosomiasis throughout sub-Saharan Africa. Both sexes of adult tsetse feed exclusively on blood and contribute to disease transmission. Notable differences between tsetse and other disease vectors include obligate microbial symbioses, viviparous reproduction, and lactation. Here, we describe the sequence and annotation of the 366-megabase Glossina morsitans morsitans genome. Analysis of the genome and the 12,308 predicted protein–encoding genes led to multiple discoveries, including chromosomal integrations of bacterial (Wolbachia) genome sequences, a family of lactation-specific proteins, reduced complement of host pathogen recognition proteins, and reduced olfaction/chemosensory associated genes. These genome data provide a foundation for research into trypanosomiasis prevention and yield important insights with broad implications for multiple aspects of tsetse biology.

Parkinson's disease (PD) is characterised by the loss of dopaminergic neurons in the midbrain. Autosomal recessive, early-onset cases of PD are predominantly caused by mutations in the parkin, PINK1 and DJ-1 genes. Animal and cellular models have verified a direct link between parkin and PINK1, whereby PINK1 phosphorylates and activates parkin at the outer mitochondrial membrane, resulting in removal of dysfunctional mitochondria via mitophagy. Despite the overwhelming evidence for this interaction, few studies have been able to identify a link for DJ-1 with parkin or PINK1. The aim of this review is to summarise the functions of these three proteins, and to analyse the existing evidence for direct and indirect interactions between them. DJ-1 is able to rescue the phenotype of PINK1-knockout Drosophila models, but not of parkin-knockouts, suggesting that DJ-1 may act in a parallel pathway to that of the PINK1/parkin pathway. To further elucidate a commonality between these three proteins, bioinformatics analysis established that Miro (RHOT1) interacts with parkin and PINK1, and HSPA4 interacts with all three proteins. Furthermore, 30 transcription factors were found to be common amongst all three proteins, with many of them being involved in transcriptional regulation. Interestingly, expression of these proteins and their associated transcription factors are found to be significantly down-regulated in PD patients compared to healthy controls. In summary, this review provides insight into common pathways linking three PD-causing genes and highlights some key questions, the answers to which may provide critical insight into the disease process.

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BackgroundIron metabolism and regulation is an indispensable part of species survival, most importantly for blood feeding insects. Iron regulatory proteins are central regulators of iron homeostasis, whose binding to iron response element (IRE) stem-loop structures within the UTRs of genes regulate expression at the post-transcriptional level. Despite the extensive literature on the mechanism of iron regulation in human, less attention has been given to insect and more specifically the blood feeding insects, where research has mainly focused on the characterization of ferritin and transferrin. We thus, examined the mechanism of iron homeostasis through a genome-wide computational identification of IREs and other enriched motifs in the UTRs of Glossina morsitans with the view to identify new IRE-regulated genes.ResultsWe identified 150 genes, of which two are known to contain IREs, namely the ferritin heavy chain and the MRCK-alpha. The remainder of the identified genes is considered novel including 20 hypothetical proteins, for which an iron-regulatory mechanism of action was inferred. Forty-three genes were found with IRE-signatures of regulation in two or more insects, while 46 were only found to be IRE-regulated in two species. Notably 39 % of the identified genes exclusively shared IRE-signatures in other Glossina species, which are potentially Glossina-specific adaptive measures in addressing its unique reproductive biology and blood meal-induced iron overload. In line with previous findings, we found no evidence pertaining to an IRE regulation of Transferrin, which highlight the importance of ferritin heavy chain and the other proposed transporters in the tsetse fly. In the context of iron-sequestration, key players of tsetse immune defence against trypanosomes have been introduced namely 14 stress and immune response genes, while 28 cell-envelop, transport, and binding genes were assigned a putative role in iron trafficking. Additionally, we identified and annotated enriched motifs in the UTRs of the putative IRE-regulated genes to derive at a co-regulatory network that maintains iron homeostasis in tsetse flies. Three putative microRNA-binding sites namely Gy-box, Brd-box and K-box motifs were identified among the regulatory motifs, enriched in the UTRs of the putative IRE-regulated genes.ConclusionBeyond our current view of iron metabolism in insects, with ferritin and transferrin as its key players, this study provides a comprehensive catalogue of genes with possible roles in the acquisition; transport and storage of iron hence iron homeostasis in the tsetse fly.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2932-7) contains supplementary material, which is available to authorized users.