Last week in Helminthology we discussed two selected papers from the emerging field of parasite genomics. As with researchers in most areas of study in the Life Sciences, researchers who study helminths (or in the case of these papers, parasitic helminths) are embracing recently developed advances in sequencing technology as a means to sequence and assemble the genomes of their study subjects. This universal embrace of the emerging field of genomics is occurring primarily due to the promise genomics offers in informing us about an organisms ecology, evolutionary history, and in the case of parasites, epidemiology and pathology. Next generations sequencing (NGS) technology, although being only seven years young, has completely changed how researchers across the world approach the study of pathogens. These two papers offer glimpses of how researchers are using these technologies to understand these pathogens, and shed light on how they have evolved into their very specific, and often amazing, life histories.
The first of these papers looked specifically at inferred metabolic pathways from ten different nematode species (Taylor et al. 2013, doi:10.1371/journal.ppat.1003505) including five Caenorhabditis species including C. elegans, and five parasitic nematodes. The purpose of this study was to identify chokepoint reactions in the metabolomes of each of these species. Chokepoint reactions were defined by the authors as any metabolic reaction that either creates a unique product, or consumes a unique substrate (see below).
Through their analysis they gained a list of inferred chokepoints for each species under study. They then conducted a comparison between the different chokepoints of each of the worms. In the end they identified a list of enzymes that may act as potential drug targets in future drug development. The details and an in-depth discussion of these results can be found below in Keyu Li’s post “From Genome to Drug”.
The other paper that was discussed at length last week was an ambitious project that sequenced and assembled the genomes (and characterized the transcriptomes) of four different platyhelminth tapeworms (Tsai et al. 2013, doi:10.1038/nature12031). Specifically this paper focused on two human infective Echinococcus species (multilocularis, and granulosus), one human infective Taenia species (solium), and one rodent tapeworm (Hymenolepis nana) that has been used as a model for studying this group of parasites. The three human infective tapeworms represent a major health concern across much of the world, including the first world, and are the first forays into creating fully assembled and annotated genomes of tapeworms.
Tapeworms don’t normally come to mind when the public is asked to think about the most severe human diseases. The consensus as to why these parasites aren’t generally perceived as a top priority in the public (as well as the research community) consciousness generally comes down to two factors. 1) The negative effects of chronic tapeworm infection are usually very subtle, and 2) Tapeworm infection is primarily a problem of the developing and third world. These two realities have led diseases caused by tapeworm to be classified as two of the seventeen neglected tropical diseases by the World Health Organization (WHO). The WHOs calculation of the negative impact of a disease uses disability adjusted life years, as opposed to the more conventional measurements of a diseases severity (such as death rates), and therefore the severity of disease caused by tapeworm (as well as numerous other parasitic helminths) are estimated as some of the greatest of all human diseases. This reality is stressed by the papers authors as justification for the large amount of technical and human resources that were required in the creation and analysis of these four tapeworm genomes.
In addition to the creation of these genomes and transcriptomes, the study also conducted a comparative study of gene family expansions and reductions which yielded some interesting findings. The gene sets involved in metabolic capacity and the absorption of nutrients were extremely skewed towards a parasitic lifestyle. Particularly the tapeworms showed marked expansions of detoxification pathways, and marked reductions in gene families involved in the metabolism of certain compounds, such as fatty acids, which are instead uptaken from the surrounding intestinal environment. Another noteworthy expansion was that of the heat shock proteins, suggesting adaptation to the extreme temperature fluctuations that helminths are forced to endure inside their hosts. Lastly, the study (similar to the metabolomic chokepoint paper (Taylor et al 2013)) assesses the transcriptomes of these worms for potential drug targets. The authors identified ~500 potential kinases, proteases, G-protien coupled receptors, and ion-channels that may potentially be utilized in the development of new anthelmintic drugs.
As a whole, these studies are a great example of how genomics can be used to inform us on the big picture of an organisms genome, which subsequently can inform us on the factors that make that organism unique. In particular, the Tsai et al. (2013) paper shows us how one can take a mass of genomic data and use it to elucidate how an organism adapts and evolves to their changing environments over time. This is certainly exciting given that none of this would have been possible just a few years ago. And it will certainly be exciting to see how the field of comparative genomics progresses into the future!