Natural selection has driven the recurrent loss of an immunity gene that protects Drosophila against a major natural parasite.

Polymorphisms in immunity genes can have large effects on susceptibility to infection. To understand the origins of this variation, we have investigated the genetic basis of resistance to the parasitoid wasp Leptopilina boulardi in Drosophila melanogaster. We found that increased expression of the gene lectin-24A after infection by parasitic wasps was associated with a faster cellular immune response and greatly increased rates of killing the parasite. lectin-24A encodes a protein that is strongly up-regulated in the fat body after infection and localizes to the surface of the parasite egg. In certain susceptible lines, a deletion upstream of the lectin-24A has largely abolished expression. Other mutations predicted to abolish the function of this gene have arisen recurrently in this gene, with multiple loss-of-expression alleles and premature stop codons segregating in natural populations. The frequency of these alleles varies greatly geographically, and in some southern African populations, natural selection has driven them near to fixation. We conclude that natural selection has favored the repeated loss of an important component of the immune system, suggesting that in some populations, a pleiotropic cost to lectin-24A expression outweighs the benefits of resistance.

Emerging Role of Extracellular Vesicles and Cellular Communication in Metastasis.

Communication between cancer cells and the surrounding stromal cells of the tumor microenvironment (TME) plays a key role in promoting metastasis, which is the major cause of cancer death. Small membrane-bound particles called extracellular vesicles (EVs) are released from both cancer and stromal cells and have a key role in mediating this communication through transport of cargo such as various RNA species (mRNA, miRNA, lncRNA), proteins, and lipids. Tumor-secreted EVs have been observed to induce a pro-tumorigenic phenotype in non-malignant cells of the stroma, including fibroblasts, endothelial cells, and local immune cells. These cancer-associated cells then drive metastasis by mechanisms such as increasing the invasiveness of cancer cells, facilitating angiogenesis, and promoting the formation of the pre-metastatic niche. This review will cover the role of EV-mediated signaling in the TME during metastasis and highlight the therapeutic potential of targeting these pathways to develop biomarkers and novel treatment strategies.