Genetics – Page 3 – David Bradley

Combined effort makes for glowing report

One of the most powerful techniques available to analytical scientists is Raman spectroscopy. Unfortunately, it is not easy to distinguish the low-intensity signals it produces when studying fluorescent species in cells because they are swamped by the much brighter glow from various cell components. Now, Dutch researchers have overcome this incompatibility to hybridize Raman with fluorescence microscopy by exploiting the optical properties of semiconductor fluorescent quantum dots (QDs). They have demonstrated hybrid Raman fluorescence spectral imaging in studies of single cells.

Biophysical engineers Henk-Jan van Manen and Cees Otto of the University of Twente, The Netherlands, have used fluorescent nanoparticles to broaden the scope of single-cell microscopy by combining it with intracellular chemical analysis based on Raman. The researchers explain that quantum dots allows weak Raman signals from DNA to shine through the ubiquitous glow from proteins and lipids.

You can read the full story in my SpectroscopyNOW column this week.

Hey good looking, what you got cooking, in those genes?

Attractive people Here’s a puzzle. If evolution ensures that ‘good’ genes spread through a population, then why are individuals so different? Why don’t people get better and better looking through each generation to the detriment of ugliness and lead to a population of real lookers?

The problem with current evolutionary theory is that it would seem that if females select the most attractive mates, then the genes responsible for their attractive features would spread quickly, leading to all males becoming equally attractive (think peacock tails). Ultimately, further sexual selection would then no longer take place and evolution would stop in its tracks.

This is the so-called lek paradox and it has remained a foil in the weaponry of the intelligent design advocate’s arsenal for many years. Until now.

Thanks to research at Newcastle University, England, this apparent fundamental flaw in Darwin’s theory of evolution, latched on to by creationists can be explained quite effectively by evolution itself. The findings of Newcastle’s Marion Petrie and Gilbert Roberts research suggests that sexual selection leads to increased genetic diversity by a mechanism not previously understood.

Petrie reasoned that as genetic mutations occur naturally anywhere in the genome, some will actually affect those used to produce the DNA repair kit enzymes found in all cells. This would lead to those individuals with a malfunctioning or inefficient repair kit, having more mutations left unrepaired and so greater variation in their genome.

Usually, damaged DNA leads to an unviable organism that either dies quickly of the effects or is otherwise unable to reproduce. However, if those variations are present in sections of the genome responsible for disease defence, then variation can actually be beneficial as greater variation in the genome at these points means more chance of warding of bacteria and viruses.

Petrie modelled the spread of genes in a population and demonstrated that the tendency towards reduction in genetic diversity caused by sexual selection is outweighed by the maintenance in greater genetic diversity generated by mutations affecting genome repair.

The researchers began this research a decade ago and their model genes are now a great fit for the observations of variations. “We find that sexual selection can promote genetic diversity despite expectations to the contrary,” Petrie says. The team publishes details of their findings today in the journal Heredity.

Power up your genome with chemistry

Post-genomic science Researchers have developed several tools to help them exploit the underlying chemistry of genomics, while novel chemistry has enabled faster, parallel sequencing methods that not only accelerate genomic research but also cut costs. The very same techniques allow sex chromosomes and complete genomes to be decoded faster and more cheaply than ever before.

Concomitantly, microfluidics technology is improving the way conventional fluorescence chemistry can be exploited in sequencing. Improved understanding of nanoscale channels – both synthetic and protein channels offers the possibility of studying individual biological macromolecules and microfabricated microarrays are opening up massively parallel opportunities. Novel chemical technologies are also opening up locked nucleic acids as well as non-DNA molecules such as microRNAs.

The so-called post-genomic era put the molecular smack in the middle of the biological quarter. Now, as cross-disciplinary communication matures, research at the intersection of chemistry and biology is working harder than ever to solve fundamental questions in science and medicine.

You can read the complete feature on the subject of chemistry in the post-genomic era from David Bradley in Science magazine today. It is the lead article on the Science Products page.

Being particular about DNA

Surface-enhanced Raman spectra (SERS) of DNA and RNA mononucleotides can be detected with high sensitivity, according to UK researchers. Using citrate-reduced silver colloidal nanoparticles aggregated with magnesium sulfate instead of the more common halide ions, reduces inappropriate enhancements and produces spectra that are sufficiently different to allow each to be distinguished.

“The main advantage of our SERS approach is that it allows direct label-free identification of mononucleotides in aqueous solution,” Steven Bell, Director of the Innovative Molecular Materials Group, at Queen’s University Belfast, explains, “There is no requirement for labels because the Raman signals of each of the mononucleotides are intrinsically different due to the differences in their chemical structures.” He adds that spectra can be obtained at ten nanograms per millilitre. “We were working with large samples but reducing the sampling volume to a few microlitres would move the sample down to tens of picograms,” he says.

More…

Genetic Variation on a Theme

What does it mean to be human? We thought that the Human Genome Project had set the limites on the genetic make-up of our species. But, according to Steve Connor, writing in the Independent today, much of the genetic variation between individuals can best be explained by the presence of multiple copies of certain key genes rather than variations in the genome sequence.

The research suggests that whereas previously we thought all people shared 99.9% of their DNA, it could be that two individuals can differ by ten times that. The research has important implications for our understanding of inherited traits and genetic disease.

The findings appear in three simultaneous papers in three leading science journals, including Nature and were reported by teams from thirteen different research centres in the UK and the US.

Who Needs Genes?

It seems that a meeting underway in Exeter this week may very well draw the conclusion that genes, the mainstay of the whole of the last half century or more of biological science, don’t actually exist, at least according to the published abstract from UPenn’s Karola Stotz and colleagues (link died since time of writing).

Stotz explains that daily findings from the life sciences continually imply that the gene as a particulate entity in the genome is not supported by the evidence. They also suggest that science journalists, as both reporters and critics, perhaps have a role to play in the public understanding of post-genomic science. Presumably, this means we should somehow be mediating the discovery of a supposed gene for this disease or that behaviour, and explaining clearly that there are very few biologists now who see “genes” as the particulate entities that explained Mendel’s findings all those years ago. Indeed, headlines shouting about an “asthma gene”, “a gene for homosexuality”, or “the gene controlling suicidal tendencies” must be spiked as of now (and maybe always should have been). I’ll be on my best behaviour in this regard from now on, although I cannot promise I don’t have the gene for being contrary and so might renege on my promise…