Genetics & Molecular Biology

Epigenetic mechanisms are at the heart of developmental biology, orchestrating the formation of many different tissues and organs from a fertilised egg. Almost all cells in an individual have exactly the same genetic material, yet behave very differently depending on which organs they comprise. Epigenetic regulation enables the fine-tuning of our genes and their expression in different places at different times, leading to the amazing complexity we see in humans despite the relatively small number of unique genes.

We all get two copies of every gene, one from our mother and one from our father. In many cases both copies are used or 'expressed’, however it is becoming clear that for some genes either the mother’s or the father’s version is used preferentially, a phenomenon known as genomic imprinting.

Specific chemical modifications to the DNA, such as methylation, appear to give the chromosomes a ‘memory’ as to their parental origin. These ‘epigenetic’ imprints, from the Greek meaning ‘on top of’, modify the structure of the DNA but not its sequence. In addition to parental modifications, it is thought that epigenetic changes may also arise in response to environmental factors, enabling an organism's genes to adapt and respond differently, even though the gene sequence does not change.

In general, domesticated food plants have larger fruits, heads of grain, tubers, etc, because this is one of the characteristics that early hunter-gatherers chose when foraging for food and later planting it.

Domesticated tomatoes can be up to 1000 times larger than their wild relatives but how did they get so big? While tomatoes have long been bred for shape, texture, flavor and nutrient composition, but it has been difficult to study these traits in tomatoes, because many of them are the result of many genes acting together.

These genes are often located in close proximity on chromosomal regions called loci, and regions with groups of genes that influence a particular trait are called quantitative trait loci (QTLs). When a trait is influenced by one gene, it is much simpler to study, but quantitative traits, like skin and eye color in humans or fruit size in tomatoes, cannot be easily defined just by crossing different individuals.

What makes a pointer point, a sheep dog herd, and a retriever retrieve? Why do Yorkshire terriers live longer than Great Danes? And how can a tiny Chihuahua possibly be related to a Great Dane?

Dogs vary in size, shape, color, coat length and behavior more than any other animal and until now, this variance has largely been unexplained. Now, scientists have developed a method to identify the genetic basis for this diversity that may have far-reaching benefits for dogs and their owners.

In the cover story of Genetics, research reveals locations in a dog's DNA that contain genes that scientists believe contribute to differences in body and skull shape, weight, fur color and length – and possibly even behavior, trainability and longevity.

In biology, everything has a history. Creationists love to try to calculate the probability of a new gene spontaneously coming into existence, but that's not how genes are born. New genes most often come from other genes: one gene gets duplicated by a freak accident (like the accidental duplication of a chunk of chromosome, a whole chromosome, or even an entire genome), so that you suddenly have a cell with two working copies of the same gene. As time goes on (that is, time on an evolutionary scale), those two duplicate genes start to divide up the work that was originally done by just one gene. One copy might end up specializing in one particular task, picking up mutations along the way that gradually transform this copy into an independent gene in its own right, with its own specialized function. From one gene, you get two, each with a distinct role in the cell.

It sounds like a nice evolutionary story, but do scientists have any real examples of duplicate genes evolving new functions?

Scientists have been trying to understand how and when we gain or lose fat cells, and now a paper in this week's issue of Nature reports that nuclear bombs are the key to solving this problem.

To understand how our bodies regulate our weight, researchers are interested in knowing how the number of fat cells changes over our lifetime - do we stop making more fat cells after adolescence? Do we keep the same fat cells all of our adult lives, or do some die off and get replaced by new ones? The typical way to study the birth and death of cells in live animals is to use radioactive tracers that label DNA, but these experiments are too toxic to try in humans. It turns out though, that the US and Soviet militaries did the experiment for us, with above-ground nuclear bomb tests in the late 1950's, tests which spewed large amounts of radioactive carbon in the atmosphere. That radioactive carbon is now in our DNA (at least for those of us alive during the cold war), and it provides a convenient "manufactured on" date for our long-lived fat cells.

Much of the coverage of autism in the media focuses on the arguments of advocates, scientists, and government officials over the relationship between vaccines and autism. But out of the spotlight, a bigger story is brewing: the hunt for autism genes, a technically difficult hunt which is pressing forward using all of the tools modern genetics has to offer. If you are like me, news stories about autism have left you with only a vague impression of the current scientific state of understanding, the impression that researchers strongly deny any link between autism and vaccines, but have little else to say about what the real cause of autism might be.

If that is your impression, you'll perhaps be surprised to learn that roughly 20% of autism cases in the US are linked to known genetic changes, a minor fraction of autism cases to be sure, but much higher than I would have guessed. That autism has a genetic basis is a well-established finding, and while this by no means rules out environmental factors, genetics is at the core of the recent progress scientists have made in understanding autism. The genetics of autism, however, is not simple - no surprise, since autism involves our most complex organ, the brain, in one of its most complex functions, social interaction. Untangling the genetic and environmental factors that underlie autism will be tough, but in the process we will learn more about how many different genes work together in a child to control the developing brain.

In 2001, the DNA sequence was published of a combination of persons. The DNA sequences of Jim Watson, discoverer of the DNA’s double helix structure, followed in 2007, and later the DNA of gene hunter Craig Venter. Recently the completion of the sequences of two Yoruba Africans was announced.

Now geneticists of Leiden University Medical Centre (LUMC) in The Netherlands have determined the first DNA sequence of a woman - and also the first European. This has been announced by the researchers this morning, during a special press conference at ‘Bessensap’, a yearly meeting of scientists and the press in the Netherlands.

Following in-depth analysis, the sequence will be made public, except incidental privacy-sensitive findings. The results will contribute to insights into human genetic diversity.

Who is Marjolein Kriek?

A new study released today in the online edition of Physiological Genomics finds that individuals with a specific genetic variation consistently consume more sugary foods. The study offers the first evidence of the role that a variation in the GLUT2 gene – a gene that controls sugar entry into the cells – has on sugar intake, and may help explain individual preferences for foods high in sugar.

Summary of the Study

Food preferences are influenced by the environment as well as genetics. Cravings for foods high in sugar vary from person to person, but the reasons why are still unclear. To better understand the mechanism, the research team examined the effect of a common variation in a gene that controls the entry of sugar (glucose) into cells.

I haven't contributed a single thing to the platypus genome project, but since my desk sits one floor above where people and robots broke the platypus DNA into chunks, cloned those chunks into bacteria, sequenced the pieces of DNA, and used massive amounts of computing power to assemble the stretches of sequence into a complete genomic whole, I'm going to consider myself somewhat of an authority on the subject and tell you what's wrong with other people's ideas about the platypus.

The genome sequence of the platypus was published Thursday in Nature, and from the press headlines, you could be excused for thinking that genomics has in fact confirmed that the platypus is a freak of nature: part bird, part reptile, and part mammal. The animal certainly looks like it - the platypus has the webbed feet and bill of a duck, and venomous spines and rubbery eggs that remind us of reptiles, but it has fur and feeds its young with milk, so it must be a mammal. The confusing press headlines might even lead you to believe that we sequenced the platypus genome just to figure out what this thing is, when the truth is, as we'll see below, that the genome sequence has essentially confirmed what evolutionary biologists have already deduced about the position of the platypus on the tree of life.

Is the platypus part bird, part reptile part mammal, an amalgam of very different groups of animals? Is it a primitive mammal that resembles the early ancestors of all mammals? Can we figure out just what this creature is by gazing at its genome?


Photo Credit: Stefan Kraft, courtesy of the Wikipedia Commons


President Bush has a bill on his desk, the Genetic Information Nondiscrimination Act (GINA), which will prohibit discrimination on the basis of genetic information with respect to health insurance and employment. He is expected to sign the bill, but is science – and the people – ready?