Academic journal article Genetics

Host Mitochondrial Association Evolved in the Human Parasite Toxoplasma Gondii Via Neofunctionalization of a Gene Duplicate

Academic journal article Genetics

Host Mitochondrial Association Evolved in the Human Parasite Toxoplasma Gondii Via Neofunctionalization of a Gene Duplicate

Article excerpt

GENE duplication is known to underlie the evolution of new gene functions and ultimately organismal phenotypes (Ohno 1970; Espinosa-Cantu et al. 2015). The expected outcome of most gene duplication events is that they will be lost by nonsense mutation and/or resolution of the locus (Ohno 1970; Lynch and Conery 2000; Lynch and Force 2000). However, those that confer a selective advantage through gene dosage, subfunctionalization, or neofunctionalization, can become fixed in the population (Ohno 1970; Lynch and Conery 2000; Lynch and Force 2000; Espinosa-Cantu et al. 2015). The phenotypic impact of locus expansions can be high in both natural and laboratory settings. When grown in noncompatible human cells, vaccinia virus was found to expand, diversify, and then contract the K3L locus, resulting in a highly adapted virus with a single K3L gene that could now disrupt the antiviral host protein Protein Kinase R (Elde et al. 2012). Laboratory studies with bacteria show that adaptation to selective conditions (stress or antibiotic exposure) via gene expansion and diversification occurs much more frequently than via point mutation (Kugelberg et al. 2006, 2010). Field studies with Drosophila spp. have identified Cyp6g1 duplication and diversification events as one source of resistance to insecticides such as dichlorodiphenyltrichloroethane (DDT) (Emerson et al. 2008; Cridland and Thornton 2010; Schmidt et al. 2010).

The examples above detail the importance of gene duplication in the evolution within species both in the laboratory and in the field. However, less is known about the impact of gene duplication and diversification events in defining species-specific traits (or even defining the species themselves, which was postulated by Ohno (1970)). It is certainly clear that there are specific gene duplication events that distinguish closely related species (such as humans and chimpanzees) (Bailey and Eichler 2006), but examples where species-specific gene expansions have been linked to species-specifictraitsare few.

Pathogens provide a unique setting in which to study the evolution and emergence of novel traits, given their large population size and the intense selective pressures placed upon them by the host. We use comparative approaches to understand the evolution of unique traits in members of Apicomplexa, a phylum of parasites of great importance in human and veterinary health. Our main focus is on Toxoplasma gondii and its near relatives. T. gondii is an important pathogen of humans, particularly in HIV/AIDS patients and the developing fetus. In addition, T. gondii is capable of infecting, causing disease in, and being transmitted by all warmblooded animals studied to date (Dubey and Sreekumar 2003).Incontrast,HammondiahammondiandNeosporacaninum have comparatively restricted host ranges and are not pathogenic in rodents or humans (Goodswen et al. 2013; Walzer et al. 2013). This is despite a high level of genetic similarity and genome-wide synteny across these three species (Reid et al. 2012; Walzer et al. 2013), and in the case of T. gondii and H. hammondi, extensive conservation of virulence effectors at both the sequence and functional levels (Walzer et al. 2013, 2014).

The unique phenotypic and life cycle features of T. gondii have most certainly contributed to its near global distribution and an incidence rate that ranges from 10 to 80% in humans. However, the genetic bases for these phenotypes are unknown, and to begin to address this question we have taken a comparative approach to identify genetic loci that are unique to T. gondii compared to H. hammondi and N. caninum.In doing so, we found that a small subset of T. gondii loci have undergone tandem duplication, expansion, and diversification only in the T. gondii lineage. Specifically, expanded loci are poorly conserved between T. gondii and its near relatives, having a higher propensity to be either missing, or not similarly expanded, in either N. caninum or H. …

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