Happy birthday, PLoS Genetics!

PLoS Genetics is celebrating its third birthday this month! Let's see what's new this week, among else...

PLoS Genetics Turns Three: Looking Back, Looking Ahead:

PLoS Genetics is three years old this month--a milestone worth celebrating! As we do, and as we recognize all who have helped us reach this point in time, we thought this would be a good opportunity to share with you a summary of our brief history and a look ahead.

Our original intent was to provide an open-access journal for the community that would "reflect the full breadth and interdisciplinary nature of genetics and genomics research by publishing outstanding original contributions in all areas of biology." Now, three years later, all of us on the Editorial Board are very pleased with the breadth of topics covered and with the diversity of approaches, organisms, and systems. Going forward, PLoS Genetics will continue to be a journal by and for the entire genetics and genomics community.

The Status of Dosage Compensation in the Multiple X Chromosomes of the Platypus:

Dosage compensation equalizes the expression of genes found on sex chromosomes so that they are equally expressed in females and males. In placental and marsupial mammals, this is accomplished by silencing one of the two X chromosomes in female cells. In birds, dosage compensation seems not to be strictly required to balance the expression of most genes on the Z chromosome between ZZ males and ZW females. Whether dosage compensation exists in the third group of mammals, the egg-laying monotremes, is of considerable interest, particularly since the platypus has five different X and five different Y chromosomes. As part of the platypus genome project, genes have now been assigned to four of the five X chromosomes. We have shown that there is some evidence for dosage compensation, but it is variable between genes. Most interesting are our results showing that there is a difference in the probability of expression for X-specific genes, with about 50% of female cells having two active copies of an X gene while the remainder have only one. This means that, although the platypus has the variable compensation characteristic of birds, it also has some level of inactivation, which is characteristic of dosage compensation in other mammals.

Pain Genes:

Pain, which afflicts up to 20% of the population at any time, provides both a massive therapeutic challenge and a route to understanding mechanisms in the nervous system. Specialised sensory neurons (nociceptors) signal the existence of tissue damage to the central nervous system (CNS), where pain is represented in a complex matrix involving many CNS structures. Genetic approaches to investigating pain pathways using model organisms have identified the molecular nature of the transducers, regulatory mechanisms involved in changing neuronal activity, as well as the critical role of immune system cells in driving pain pathways. In man, mapping of human pain mutants as well as twin studies and association studies of altered pain behaviour have identified important regulators of the pain system. In turn, new drug targets for chronic pain treatment have been validated in transgenic mouse studies. Thus, genetic studies of pain pathways have complemented the traditional neuroscience approaches of electrophysiology and pharmacology to give us fresh insights into the molecular basis of pain perception.

Stable in a Genome of Instability: An Interview with Evan Eichler:

We like to think that our genome is rock-solid, that it is dependable, there for us when we need it. The truth is far from that. By fits and starts, our species' collective genome is undulating, reshaping itself with eruptions of genomic lava and clashes of sequence tectonics, at once both marvelous and unsettling. We are unaware of this tumult within us until we are confronted with disease in ourselves, our friends, or our family.

Evan Eichler is a man obsessed with this process, and to speak with him is a study in contrasts (Image 1). An unassuming Canadian, Eichler is a student of genomic architecture, the arrangement of sequences in our genome, and their evolution. Eichler grew up on a farm in Manitoba, married his college sweetheart, and now lives together with her and their four children in the mountains east of Seattle. As we walked up the hill to my office during his recent visit to UCSF, he talked about being an early riser, taking his son to band practice before school, and then driving the 30 miles to work in his Toyota. Eichler is a man bristling with excitement for his discoveries, but holding it in check by a tradition of modesty. He has consistently followed his own path, chosen career opportunities that were dictated not by politics or peer pressure but rather by what feels like a good fit for him.

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