3 tera-basepairs as a fundamental limit for robust DNA replication

10 p.-2 tab.In order to maintain functional robustness and species integrity, organisms must ensure high fidelity of the genome duplication process. This is particularly true during early development, where cell division is often occurring both rapidly and coherently. By studying the extreme limits of suppressing DNA replication failure due to double fork stall errors, we uncover a fundamental constant that describes a trade-off between genome size and architectural complexity of the developing organism. This constant has the approximate value N_U ≈ 3×10^12 basepairs, and depends only on two highly conserved molecular properties of DNA biology. We show that our theory is successful in interpreting a diverse range of data across the Eukaryota.MAM, LA and TJN acknowledge prior support from the Scottish Universities Life Sciences Alliance. JJB acknowledges support from Cancer Research UK (grant C303/A14301) and the Wellcome Trust (grant WT096598MA). TJN acknowledges prior support from the National Institutes of Health (Physical Sciences in Oncology Centers, U54 CA143682).Peer reviewe

Culture and Cancer

Genetic mechanisms, since they broadly involve information transmission, should be translatable into information dynamics formalism. From this perspective we reconsider the adaptive mutator, one possible means of 'second order selection' by which a highly structured 'language' of environment and development writes itself onto the variation upon which evolutionary selection and tumorigenesis operate. Our approach uses recent results in the spirit of the Large Deviations Program of applied probability that permit transfer of phase transition approaches from statistical mechanics to information theory, generating evolutionary and developmental punctuation in what we claim to be a highly natural manner

Global divergence of microbial genome sequences mediated by propagating fronts

We model the competition between recombination and point mutation in microbial genomes, and present evidence for two distinct phases, one uniform, the other genetically diverse. Depending on the specifics of homologous recombination, we find that global sequence divergence can be mediated by fronts propagating along the genome, whose characteristic signature on genome structure is elucidated, and apparently observed in closely-related {\it Bacillus} strains. Front propagation provides an emergent, generic mechanism for microbial "speciation", and suggests a classification of microorganisms on the basis of their propensity to support propagating fronts

Toward Cultural Oncology: The Evolutionary Information Dynamics of Cancer

'Racial' disparities among cancers, particularly of the breast and prostate, are something of a mystery. For the US, in the face of slavery and its sequelae, centuries of interbreeding have greatly leavened genetic differences between 'Blacks' and 'whites', but marked contrasts in disease prevalence and progression persist. 'Adjustment' for socioeconomic status and lifestyle, while statistically accounting for much of the variance in breast cancer, only begs the question of ultimate causality. Here we propose a more basic biological explanation that extends the theory of immune cognition to include elaborate tumor control mechanisms constituting the principal selection pressure acting on pathologically mutating cell clones. The interplay between them occurs in the context of an embedding, highly structured, system of culturally specific psychosocial stress which we find is able to literally write an image of itself onto disease progression. The dynamics are analogous to punctuated equilibrium in simple evolutionary proces

Construction of membrane-bound artificial cells using microfluidics: a new frontier in bottom-up synthetic biology

The quest to construct artificial cells from the bottom-up using simple building blocks has received much attention over recent decades and is one of the grand challenges in synthetic biology. Cell mimics that are encapsulated by lipid membranes are a particularly powerful class of artificial cells due to their biocompatibility and the ability to reconstitute biological machinery within them. One of the key obstacles in the field centres on the following: how can membrane-based artificial cells be generated in a controlled way and in high-throughput? In particular, how can they be constructed to have precisely defined parameters including size, biomolecular composition and spatial organization? Microfluidic generation strategies have proved instrumental in addressing these questions. This article will outline some of the major principles underpinning membrane-based artificial cells and their construction using microfluidics, and will detail some recent landmarks that have been achieved