アイテム詳細

要旨

Nematodes of the genus Strongyloides are obligate parasites of various vertebrates (including man) and are thus of economic and medical significance due to their disease-causing ability. Interestingly, the life cycle of Strongyloides nematodes consists of 2 distinct generations, a parasitic one within the vertebrate host and a free-living one outside the host. This free-living generation is almost unique among nematode parasites of vertebrates. Ease of access and methods for cultivating this generation are proving important for understanding the molecular basis of true parasites. For the purpose of my thesis, I have chosen to work on 3 different aspects of the previously poorly understood reproductive biology of Strongyloides, namely:- I. sex determination, with an aim to create a better understanding of sex chromosome evolution within this genus; II. identifying the boundaries and mechanisms of chromatin diminution in the males of S. papillosus; and III. a detailed characterization of the Strongyloides spp. germ line in comparison to the well-studied nematode C. elegans. There are 3 sex determining systems described for Strongyloides species: the XX/X0 system, where females have 2 X-chromosomes but males only one; sex specific chromatin diminution, wherein males are determined by the loss of an internal portion of a chromosome; and an environmental one, with no karyotypic differences between the sexes. I could show that XX/X0 sex determination is ancestral within Strongyloididae, suggesting that chromatin diminution in particular is a derived state. This has given us an understanding of the rapid evolution of sex determining mechanisms and sex chromosomes within this genus by allowing us to correlate the evolutionary life histories of reproduction with chromosome structure. Further, through molecular and genetic tools, I have identified the boundaries on the chromosome where chromatin diminution occurs in the males of S. papillosus and speculated about the cellular mechanisms that might govern this event. In the process, I have contributed significantly in sequencing, annotating and improving the existing S. papillosus genome assembly. Finally, I have characterized the germ line of 3 closely related Strongyloididae members (S. ratti, S. papillosus and P. trichosuri). Specifically, I have studied differential chromatin amplification in some germ nuclei, the absence of stem cell populations and germ cell divisions, differential control of gametogenesis and the differences in germ line chromatin, i.e histone modification patterns. My results reveal striking differences in development, organization and fluid dynamics of the Strongyloididae germ line, both between the different Strongyloididae species and in comparison to C. elegans. This study thus showcases Strongyloides as a promising genus for basic biological and evolutionary research. More importantly it provides the much needed understanding of the reproductive biology of these emerging and medically relevant parasitic nematodes.