This review considers available evidence for mechanisms of conferred adaptive advantages in the face of specific infectious diseases. In short, we explore a number of genetic conditions, which carry some benefits in adverse circumstances including exposure to infectious agents. The examples discussed are conditions known to result in resistance to a specific infectious disease, or have been proposed as being associated with resistance to various infectious diseases. These infectious disease—genetic disorder pairings include malaria and hemoglobinopathies, cholera and cystic fibrosis, tuberculosis and Tay-Sachs disease, mycotic abortions and phenylketonuria, infection by enveloped viruses and disorders of glycosylation, infection by filoviruses and Niemann–Pick C1 disease, as well as rabies and myasthenia gravis. We also discuss two genetic conditions that lead to infectious disease hypersusceptibility, although we did not cover the large number of immunologic defects leading to infectious disease hypersusceptibilities. Four of the resistance-associated pairings (malaria/hemogloginopathies, cholera/cystic fibrosis, tuberculosis/Tay-Sachs, and mycotic abortions/phenylketonuria) appear to be a result of selection pressures in geographic regions in which the specific infectious agent is endemic. The other pairings do not appear to be based on selection pressure and instead may be serendipitous. Nonetheless, research investigating these relationships may lead to treatment options for the aforementioned diseases by exploiting established mechanisms between genetically affected cells and infectious organisms. This may prove invaluable as a starting point for research in the case of diseases that currently have no reliably curative treatments, e.g., HIV, rabies, and Ebola.

BackgroundOver one third of all animal phyla utilize a mode of early embryogenesis called ‘spiral cleavage’ to divide the fertilized egg into embryonic cells with different cell fates. This mode is characterized by a series of invariant, stereotypic, asymmetric cell divisions (ACDs) that generates cells of different size and defined position within the early embryo. Astonishingly, very little is known about the underlying molecular machinery to orchestrate these ACDs in spiral-cleaving embryos. Here we identify, for the first time, cohorts of factors that may contribute to early embryonic ACDs in a spiralian embryo.ResultsTo do so we analyzed stage-specific transcriptome data in eggs and early embryos of the spiralian annelid Platynereis dumerilii for the expression of over 50 candidate genes that are involved in (1) establishing cortical domains such as the partitioning defective (par) genes, (2) directing spindle orientation, (3) conveying polarity cues including crumbs and scribble, and (4) maintaining cell-cell adhesion between embryonic cells. In general, each of these cohorts of genes are co-expressed exhibiting high levels of transcripts in the oocyte and fertilized single-celled embryo, with progressively lower levels at later stages. Interestingly, a small number of key factors within each ACD module show different expression profiles with increased early zygotic expression suggesting distinct regulatory functions. In addition, our analysis discovered several highly co-expressed genes that have been associated with specialized neural cell-cell recognition functions in the nervous system. The high maternal contribution of these ‘neural’ adhesion complexes indicates novel general adhesion functions during early embryogenesis.ConclusionsSpiralian embryos are champions of ACD generating embryonic cells of different size with astonishing accuracy. Our results suggest that the molecular machinery for ACD is already stored as maternal transcripts in the oocyte. Thus, the spiralian egg can be viewed as a totipotent yet highly specialized cell that evolved to execute fast and precise ACDs during spiral cleaving stages. Our survey identifies cohorts of factors in P. dumerilii that are candidates for these molecular mechanisms and their regulation, and sets the stage for a functional dissection of ACD in a spiral-cleaving embryo.Electronic supplementary materialThe online version of this article (10.1186/s12861-017-0158-9) contains supplementary material, which is available to authorized users.

Background viii Results viii Conclusions ix CHAPTER 1: BACKGROUND 1 (1) Cortical Domain Establishment 8 (2) Spindle Orientation 9 (3) Polarity Complexes 9 (4) Cell-cell adhesions and cell adhesion complexes CHAPTER 2: METHODS 12 Platynereis dumerilii culture Transcriptome assembly Identification of orthologous genes by in silico searches Cloning of ACD genes Whole mount in situ hybridization CHAPTER 3: RESULTS 16 Identification and classification of ACD genes Category I. Establishing cortical domains: The PAR gene complexes Category II: The machinery to orient the mitotic spindle Category III: Establishing and maintaining cell polarity Category 4: Mediators of Cell-Cell Adhesion Transcripts for ACD components in the unfertilized egg (0 hpf) and zygote (2 hpf) CHAPTER 4: DISCUSSION 47 Survey of ACD components in the spiralian: P. dumerilii Asymmetric cell division in other spiralians Asymmetric cell divisions in P. dumerilii High maternal contribution of ACD components: a general phenomenon? Fast removal of maternal ACD transcripts Early zygotic transcription of key ACD components Scarce ACD transcripts: missing ACD components? Similarity in expression domains: Co-expression of ACD components Neural cell recognition complexes in early embryogenesis Conclusion APPENDIX A: SUPPLEMENTAL FIGURE 1 58