Looking at the tree of life, descent with modification is an obvious theme, where genes are passed on through ‘vertical’ lines of ancestry. It so happens though that genes can jump from one lineage to another, by a process called ‘horizontal gene transfer’ (HGT). Naked DNA uptake (transformation), viruses (transduction), and plasmids (conjugation) are the mechanisms by which the genetic units of heredity need not be inherited in the usual sense. HGT appears to blur the boundaries of what a species is, particularly for the bacterial domain of life. So the study published by Rotem Sorek, Edward Rubin et al.¹ on the determination of barriers to HGT is interesting from a couple different perspectives. Read more »

Here’s one of my favorite journal articles from the past year - an elegant study by Natalie Andrew and Robert Insall published in Nature Cell Biology: Chemotaxis in shallow gradients is mediated independently of PtdIns 3-kinase by biased choices between random protrusions. From the introduction:

We have made detailed, quantitative observations of Dictyostelium cells chemotaxing in shallow gradients, which contradict current models in several ways (see Supplementary Information, Fig. S1): first, new pseudopods are made in spatially restricted sites by splitting of the leading edge; second, the timing and direction of these new pseudopods are random, so they cannot correct the cell’s direction; and third, the survival and retraction of pseudopods are spatially controlled, suggesting an alternative mechanism of chemotaxis.

This model is very similar to the mechanism of growth cone guidance, where random protrusions are constantly exploring the cell’s surroundings, ‘tasting’ for attractant or repellant cues. These cues either stabilize or destabilize one side of the growth cone or pseudopod over the other side, causing the cell to turn one way or another. This isn’t a new concept (having been addressed in neutrophils previously - Arrieumerlou and Meyer, 2005), but Andrew and Insall formalize the case for biased choices in chemotaxis in Dictyostelium very nicely (Figure 1, below).

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In the budding yeast Saccharomyces cerevisiae, 59 of the 79 cytoplasmic ribosomal proteins are encoded by two genes, stemming from an ancient genome duplication event. Komili et al. (2007) now report that these paralogous genes are not functionally equivalent, suggesting the possible existence of a “ribosome code.”¹

Yeast and mammalian genomes are riddled with apparently duplicated genes, differing in only a few amino acids from one paralogue to its clone. Because they’re so nearly identical, most researchers assume some degree of redundancy in such circumstances, and attempt to ascertain the function of only one of the two. If there is any difference in function between two paralogues, the difference might be unimportant, or just too difficult to tease apart experimentally.

As we gain more and more insight into how the cell works, such minutiae might be a curious area to study up on. In the case of the yeast S. cerevisiae, it turns out that 59 of their 78 ribosomal proteins have doubles that differ by only a few amino acids. Suzanne Komili, Pamela Silver (Harvard Medical School, Boston, MA), and colleagues² make an intriguing argument that only rarely are individual members of a paralogous gene pair functionally identical, despite this strong sequence similarity. Read more »

Apoptosis, or programmed cell death, is an evolutionarily conserved and neatly orchestrated process important for tissue remodeling and safe elimination of severely damaged cells. Conducted by a caspase-mediated proteolytic cascade, the cell death program results in a series of cellular changes distinct from cellular necrosis. And one of the critical aspects that distinguish apoptosis from necrosis is that intracellular components of apoptotic cells are isolated, preventing membrane permeability and release of inflammatory molecules.

Just how do dying cells keep themselves from spilling out their materials into the surrounding tissues? And what role do the cytoskeleton components have in this process? Those are the questions that José Sánchez-Alcázar and colleagues¹ asked in a paper in July’s issue of the journal Apoptosis. Read more »

“How many genes are mutated in a human tumor?” That’s the question that a team of researchers at Johns Hopkins posed, and took a comparative genomic approach. By analyzing the sequences of 20,857 transcripts from 18,191 human genes, in 11 breast and 11 colorectal cancers, Wood et al. were able to generate a topographical representation of gene mutations. The average number of mutations per tumor was approximately 80, but ranged from 39 to 193.

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One of the neat tools in molecular biology is the ability to recombine parts of two proteins to create fusion or chimeras. They’re often extremely useful for simple experiments, some of the time for targeting protein domains to subcellular sites, or to isolate a structural component of a protein. The functional information is often quite interesting.

One manuscript recently in Nature Precedings used the chimeric molecule approach slightly differently. John Rossi and coworkers describe a aptamer conjugate for delivering anti-HIV siRNA specificially to infected cells. The aptamer in question is a gp120-interacting molecule. The envelope glycoprotein gp120 is expressed on the surface of HIV-1 infected cells, allowing binding and interalization of the whatever is conjugated to the aptamer, in concept. In this case, Rossi et al. have conjugated the chimera to an siRNA that releases an anti-tat/rev siRNA, which in turn inhibits HIV replication. Read more »

This month’s Nature Genetics has an article introduced with the catchy title Aging and cancer: killing two birds with one worm. That’s referring to using C. elegans as a model organism, of course, due to its utility as a model organism for genetic research.

Pinkston-Gosse and Kenyon follow a C. elegans-ortholog of FOXO transcription factors, DAF-16, to phenotypes of manipulated lifespans and cancer susceptability. The pathway stems from the respective ortholog of insulin/insulin-like growth factor 1 (IGF-1) receptors, and FOXO transcription factors turn on genes involved in p53-dependent apoptosis, cell cycle arrest, and cellular stress resistance.
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Three papers from UC Davis have appeared on the PLoS journals in the past few days that bring together population genetics and genomic sequencing to address questions of importance to evolutionary biology. Their discussions of divergence in coding versus non-coding, and adaptive versus neutral shifts, are what caught my eye. Collectively, they’re three very densely packed studies, providing a fountain of info that only bioinformatics can process. Read more »

….statistics. The very word strikes fear into the heart of many a biologist (including me). In an article published earlier this year, Cumming and co-workers of La Trobe University, Melbourne gave a very useful rundown of common mistakes made when using statistical error bars in biology and suggested a number of rules that should be adhered to when presenting data in this way, especially in publications. The article provides a quick taster of their advice, which helps to make things seem a little less scary.

Two types of error bars are commonly used in biology. Descriptive error bars used to describe a data set and inferential error bars used to determine which conclusions can be justifiably drawn from a data set. These are summarized in the table on the right, which is taken from the paper. Read more »

Gene regulatory network (GRN) circuits are collections of DNA segments in a cell which interact with each other (indirectly through their RNA and protein expression products) and with other substances in the cell, thereby governing the rates at which genes in the network are transcribed into mRNA. A lot of research has gone into (a) identifying components of GRNs and (b) developing mathematical models describing their dynamic spatial and temporal interactions. Molecular and cell biologists have a lot to offer in explaining embryonic development from the former perspective.

Eric Davidson’s lab at Caltech has been working on this for a few years, with a recent paper in Science on such findings in sea urchin embryos.
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