Life history effects on neutral polymorphism and divergence rates, in autosomes and sex chromosomes

Much of modern population genetics revolves around neutral genetic differences among individuals, populations, and species. In this dissertation, I study how sex-specific life history traits affects neutral diversity levels within populations (polymorphism) and between species (divergence) on autosomes and sex chromosomes. In chapter 1, I consider the effects of sex specific life histories, and particularly generation times, on substitution rates along the great ape phylogeny. Using a model that approximates features of the mutational process in most mammals, and fitting the model on data from pedigree-studies in humans, I predict the effects of life history traits on specific great ape lineages. As I show, my model can account for a number of seemingly disparate observations: notably, the puzzlingly low X-to-autosome ratios of substitution rates in humans and chimpanzees and differences in rates of autosomal substitutions among great ape lineages. The model further suggests how to translate pedigree-based estimates of human mutation rates into split times among extant apes, given sex-specific life histories. In so doing, it largely bridges the gap reported traditional fossil-based estimates of mutation rates, and recent pedigree-based estimates. In chapter 2, I consider the effects of sex- and age- dependent mortalities, fecundities, reproductive variances and mutation rates on polymorphism levels in humans. Using a coalescence framework, I provide closed formulas for the expected polymorphism rate, accounting for life history effects. These formulas generalize and simplify previous models. Applying the model to humans, my results suggest that the effects of life history – and of sex differences in generation times in particular – attenuate how changes in historical population sizes affect X to autosome polymorphism ratios. Applying these results to observations across human populations, I find that life history effects and demographic histories can largely explain the reduction in X to autosome polymorphism ratios outside Africa. More generally, my work elucidates the major role of sex-specific life history traits – and male and female generation times in particular – in shaping patterns of neutral genetic diversity within and between species

Painful angiomyxoid tumor in a failed renal allograft presenting as post-transplant lymphoproliferative disorder

Introduction: There exist few reports of de novo tumors involving an allograft kidney, and to the best of our knowledge there are only two previous reports of angiomyxoma Case Presentation: A 53-year-old Caucasian male with end-stage renal disease (ESRD) on hemodialysis (HD) secondary to malakoplakia with three failed prior renal transplants presented for repeat transplant evaluation. Imaging demonstrated a mass of the transplanted kidney suggestive of posttransplant lymphoproliferative disease (PTLPD). A biopsy was obtained revealing a predominance of myxoid material. The patient became increasingly symptomatic from the mass and underwent a palliative right transplant nephrectomy. Final pathology revealed angiomyxoid tumor. Conclusions: Angiomyxomas are asymptomatic, appear as PTLD on imaging and should be considered in the differential diagnosis of masses occurring in renal transplant allografts