The evolution of BioBike: Community adaptation of a biocomputing platform

Programming languages are, at the same time, instruments and communicative artifacts that evolve rapidly through use. In this paper I describe an online computing platform called BioBike. BioBike is a trading zone where biologists and programmers collaborate in the development of an extended vocabulary and functionality for computational genomics. In the course of this work they develop interactional expertise with one another’s domains. The extended BioBike vocabulary operates on two planes: as a working programming language, and as a pidgin in the conversation between the biologists and engineers. The flexibility that permits this community to dynamically extend BioBike’s working vocabulary—to form new pidgins—makes BioBike unique among computational tools, which usually are not themselves adapted through the collaborations that they facilitate. Thus BioBike is itself a crucial feature—which it is tempting to refer to as a participant—in the developing interaction.     

The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy

Although murine X-linked muscular dystrophy (mdx) and Duchenne muscular dystrophy (DMD) are genetically homologous and both characterized by a complete absence of dystrophin, the limb muscles of adult mdx mice suffer neither the detectable weakness nor the progressive degeneration that are features of DMD. Here we show that the mdx mouse diaphragm exhibits a pattern of degeneration, fibrosis and severe functional deficit comparable to that of DMD limb muscle, although adult mice show no overt respiratory impairment. Progressive functional changes include reductions in strength (to 13.5% of control by two years of age), elasticity, twitch speed and fibre length. The collagen density rises to at least seven times that of control diaphragm and ten times that of mdx hind-limb muscle. By 1.5 years of age, similar but less severe histological changes emerge in the accessory muscles of respiration. On the basis of these findings, we propose that dystrophin deficiency alters the threshold for work-induced injury. Our data provide a quantitative framework for studying the pathogenesis of dystrophy and extend the application of the mdx mouse as an animal model.     

Myosin gene mutation correlates with anatomical changes in the human lineage

Powerful masticatory muscles are found in most primates, including chimpanzees and gorillas, and were part of a prominent adaptation of Australopithecus and Paranthropus, extinct genera of the family Hominidae. In contrast, masticatory muscles are considerably smaller in both modern and fossil members of Homo. The evolving hominid masticatory apparatus--traceable to a Late Miocene, chimpanzee-like morphology--shifted towards a pattern of gracilization nearly simultaneously with accelerated encephalization in early Homo. Here, we show that the gene encoding the predominant myosin heavy chain (MYH) expressed in these muscles was inactivated by a frameshifting mutation after the lineages leading to humans and chimpanzees diverged. Loss of this protein isoform is associated with marked size reductions in individual muscle fibres and entire masticatory muscles. Using the coding sequence for the myosin rod domains as a molecular clock, we estimate that this mutation appeared approximately 2.4 million years ago, predating the appearance of modern human body size and emigration of Homo from Africa. This represents the first proteomic distinction between humans and chimpanzees that can be correlated with a traceable anatomic imprint in the fossil record.