Genomic island variability facilitates Prochlorococcus-virus coexistence

Prochlorococcus cyanobacteria are extremely abundant in the oceans, as are the viruses that infect them. How hosts and viruses coexist in nature remains unclear, although the presence of both susceptible and resistant cells may allow this coexistence. Combined whole-genome sequencing and PCR screening technology now enables us to investigate the effect of resistance on genome evolution and the genomic mechanisms behind the long-term coexistence of Prochlorococcus and their viruses. Here we present a genome analysis of 77 substrains selected for resistance to ten viruses, revealing mutations primarily in non-conserved, horizontally transferred genes that localize to a single hypervariable genomic island. Mutations affected viral attachment to the cell surface and imposed a fitness cost to the host, manifested by significantly lower growth rates or a previously unknown mechanism of more rapid infection by other viruses. The mutant genes are generally uncommon in nature yet some carry polymorphisms matching those found experimentally. These data are empirical evidence indicating that viral-attachment genes are preferentially located in genomic islands and that viruses are a selective pressure enhancing the diversity of both island genes and island gene content. This diversity emerges as a genomic mechanism that reduces the effective host population size for infection by a given virus, thus facilitating long-term coexistence between viruses and their hosts in nature.     

Mutations in SUFU predispose to medulloblastoma

Enchondromas are common benign cartilage tumors of bone. They can occur as solitary lesions or as multiple lesions in enchondromatosis (Ollier and Maffucci diseases). Clinical problems caused by enchondromas include skeletal deformity and the potential for malignant change to chondrosarcoma. The extent of skeletal involvement is variable in enchondromatosis and may include dysplasia that is not directly attributable to enchondromas. Enchondromatosis is rare, obvious inheritance of the condition is unusual and no candidate loci have been identified. Enchondromas are usually in close proximity to, or in continuity with, growth-plate cartilage. Consequently, they may result from abnormal regulation of proliferation and terminal differentiation of chondrocytes in the adjoining growth plate. In normal growth plates, differentiation of proliferative chondrocytes to post-mitotic hypertrophic chondrocytes is regulated in part by a tightly coupled signaling relay involving parathyroid hormone related protein (PTHrP) and Indian hedgehog (IHH). PTHrP delays the hypertrophic differentiation of proliferating chondrocytes, whereas IHH promotes chondrocyte proliferation. We identified a mutant PTH/PTHrP type I receptor (PTHR1) in human enchondromatosis that signals abnormally in vitro and causes enchondroma-like lesions in transgenic mice. The mutant receptor constitutively activates Hedgehog signaling, and excessive Hedgehog signaling is sufficient to cause formation of enchondroma-like lesions.     

Propagating solitary waves along a rapidly moving crack front

A rapidly moving crack in a brittle material is often idealized as a one-dimensional object with a singular tip, moving through a two-dimensional material. However, in real three-dimensional materials, tensile cracks form a planar surface whose edge is a rapidly moving one-dimensional singular front. The dynamics of these fronts under repetitive interaction with material inhomogeneities (asperities) and the morphology of the fracture surface that they create are not yet understood. Here we show that perturbations to a crack front in a brittle material result in long-lived and highly localized waves, which we call 'front waves' These waves exhibit a unique characteristic shape and propagate along the crack front at approximately the Rayleigh wave speed (the speed of sound along a free surface). Following interaction, counter-propagating front waves retain both their shape and amplitude. They create characteristic traces along the fracture surface, providing cracks with both inertia and a new mode of dissipation. Front waves are intrinsically three-dimensional, and cannot exist in conventional two-dimensional theories of fracture. Because front waves can transport and distribute asperity-induced energy fluctuations throughout the crack front, they may help to explain how cracks remain a single coherent entity, despite repeated interactions with randomly dispersed asperities.