Evolution: vertebrate reproductive strategies get mixed up

The mangrove killifish is the only vertebrate known to have a mixed-mating strategy, where hermaphrodites reproduce by either self-fertilisation or cross-breeding. New molecular evidence from this species reveals that occasional cross-breeding between common hermaphroditic individuals and rare pure males results in an injection of genetic variation into otherwise highly homozygous 'clonal' lineages.     

How flies get their size: genetics meets physiology

Body size affects important fitness variables such as mate selection, predation and tolerance to heat, cold and starvation. It is therefore subject to intense evolutionary selection. Recent genetic and physiological studies in insects are providing predictions as to which gene systems are likely to be targeted in selecting for changes in body size. These studies highlight genes and pathways that also control size in mammals: insects use insulin-like growth factor (IGF) and Target of rapamycin (TOR) kinase signalling to coordinate nutrition with cell growth, and steroid and neuropeptide hormones to terminate feeding after a genetically encoded target weight is achieved. However, we still understand little about how size is actually sensed, or how organ-intrinsic size controls interface with whole-body physiology.     

How microtubules get fluorescent speckles.

The dynamics of microtubules in living cells can be seen by fluorescence microscopy when fluorescently labeled tubulin is microinjected into cells, mixing with the cellular tubulin pool and incorporating into microtubules. The subsequent fluorescence distribution along microtubules can appear "speckled" in high-resolution images obtained with a cooled CCD camera (Waterman-Storer and Salmon, 1997. J. Cell Biol. 139:417-434). In this paper we investigate the origins of these fluorescent speckles. In vivo microtubules exhibited a random pattern of speckles for different microtubules and different regions of an individual microtubule. The speckle pattern changed only after microtubule shortening and regrowth. Microtubules assembled from mixtures of labeled and unlabeled pure tubulin in vitro also exhibited fluorescent speckles, demonstrating that cellular factors or organelles do not contribute to the speckle pattern. Speckle contrast (measured as the standard deviation of fluorescence intensity along the microtubule divided by the mean fluorescence intensity) decreased as the fraction of labeled tubulin increased, and it was not altered by the binding of purified brain microtubule-associated proteins. Computer simulation of microtubule assembly with labeled and unlabeled tubulin showed that the speckle patterns can be explained solely by the stochastic nature of tubulin dimer association with a growing end. Speckle patterns can provide fiduciary marks in the microtubule lattice for motility studies or can be used to determine the fraction of labeled tubulin microinjected into living cells.     

How does protein folding get started?

Three models for the initiation of protein folding are considered in the light of recent experiments. The three models emphasize the possible roles of: (1) a hydrophobic collapse, (2) formation of secondary structure, or (3) formation of one or more specific interactions. Whether these models are likely to be contradictory or complementary is discussed.     

How Cancer Shapes Evolution and How Evolution Shapes Cancer

Evolutionary theories are critical for understanding cancer development at the level of species as well as at the level of cells and tissues, and for developing effective therapies. Animals have evolved potent tumor-suppressive mechanisms to prevent cancer development. These mechanisms were initially necessary for the evolution of multi-cellular organisms and became even more important as animals evolved large bodies and long lives. Indeed, the development and architecture of our tissues were evolutionarily constrained by the need to limit cancer. Cancer development within an individual is also an evolutionary process, which in many respects mirrors species evolution. Species evolve by mutation and selection acting on individuals in a population; tumors evolve by mutation and selection acting on cells in a tissue. The processes of mutation and selection are integral to the evolution of cancer at every step of multistage carcinogenesis, from tumor genesis to metastasis. Factors associated with cancer development, such as aging and carcinogens, have been shown to promote cancer evolution by impacting both mutation and selection processes. While there are therapies that can decimate a cancer cell population, unfortunately cancers can also evolve resistance to these therapies, leading to the resurgence of treatment-refractory disease. Understanding cancer from an evolutionary perspective can allow us to appreciate better why cancers predominantly occur in the elderly and why other conditions, from radiation exposure to smoking, are associated with increased cancers. Importantly, the application of evolutionary theory to cancer should engender new treatment strategies that could better control this dreaded disease.     

How does the immune response get started?

An effective adaptive immune response requires the prior induction of the regulatory effector T-helper (eTh). There are two competing models of how this cell is induced to effectors. Under the Associative Recognition of Antigen (ARA) or “two signal” model, the T-helper requires eTh in order to be induced to eTh, an “autocatalytic” process. Under the “costimulation” model eTh are induced by an antigen-unspecific signal derived from an “activated” APC. Under the ARA model the problem of the origin of the primer eTh is posed. A nonself antigen-independent pathway to eTh is proposed as well as an experiment to reveal its existence. In the costimulation framework no primer eTh need be postulated but it lacks a mechanism that, in the absence of ARA, accounts for the self-nonself discrimination and the determination of effector class.     

How not to get cross(ed)

Comment on: Lorenz A, et al. Science 2012; 336:1585-8.