all genomics stories

‘Speed limit’ found on rate of evolution

jake — Mon, 22 Oct 2007 13:10:24 -0400

Harvard University scientists have identified a virtual “speed limit” on the rate of molecular evolution in organisms, and the magic number appears to be six mutations per genome per generation — a rate of change beyond which species run the strong risk of extinction as their genomes lose stability.

By modeling the stability of proteins required for an organism’s survival, Eugene Shakhnovich and his colleagues have discovered this essential thermodynamic limit on a species’ rate of evolution. Their discovery, published this week in the Proceedings of the National Academy of Sciences, draws a crucial connection between the physical properties of genetic material and the survival fitness of an entire organism.

First robust genetic link to height in humans identified

404132862 — Thu, 06 Sep 2007 11:55:03 -0400

Over a century ago, scientists first proposed that height is a complex trait — one influenced by environmental factors and multiple genes. While subsequent studies revealed that most of the variation in adult height is genetically determined, there has been little success in pinpointing the responsible genes. Some clues have come from rare syndromes of extreme height or shortness caused by severe alterations in specific gene sequences, but by and large, these changes do not explain the normal spectrum of human height.

Opossum genome shows 'junk' DNA source of genetic innovation

50443248 — Wed, 09 May 2007 16:51:38 -0400

A tiny opossum's genome has shed light on how evolution creates new creatures from old, showing that change primarily comes by finding new ways of turning existing genes on and off.

The research, by an international consortium led by the Broad Institute of MIT and Harvard, revises our understanding of genetic evolution. Scientists previously thought that evolution slowly changed the genes that create specific proteins. As the proteins changed, so did the creatures that owned them.

The current research shows that opossum and human protein-coding genes have changed little since their ancestors parted ways, 180 million years ago. It has been the regulation of their genes - when they turn on and off - that has changed dramatically.

"Evolution is tinkering much more with the controls than it is with the genes themselves," said Broad Institute director Eric Lander. "Almost all of the new innovation ... is in the regulatory controls. In fact, marsupial mammals and placental mammals have largely the same set of protein-coding genes. But by contrast, 20 percent of the regulatory instructions in the human genome were invented after we parted ways with the marsupial."

The research, released May 9 also illustrated a mechanism for those regulatory changes. It showed that an important source of genetic innovation comes from bits of DNA, called transposons, that make up roughly half of our genome and that were previously thought to be genetic "junk."

The research shows that this so-called junk DNA is anything but, and that it instead can help drive evolution by moving between chromosomes, turning genes on and off in new ways.

Despite their heft, many dinosaurs had surprisingly tiny genomes

Wed, 11 Jul 2007 09:46:11 -0400

They might be giants, but many dinosaurs apparently had genomes no larger than those of a modern hummingbird.

So say scientists who've linked bone cell and genome size among living species and then used that new understanding to gauge the genome sizes of 31 species of extinct dinosaurs and birds, whose bone cells can be measured from fossilized bones.

The researchers, at Harvard University and the University of Reading, were led by Chris Organ and Scott V. Edwards at Harvard. They report their findings this week in the journal Nature.

Genome-wide map will help fight diabetes

Wed, 11 Jul 2007 10:57:51 -0400

The Broad Institute of MIT and Harvard, Lund University, and Novartis have announced the completion of a genome-wide map of genetic differences in humans and their relationship to type 2 diabetes and other metabolic disorders. All results of the analysis are being made accessible, free of charge, on the Internet to scientists around the world.

The work is the result of a pioneering public-private collaboration known as the Diabetes Genetics Initiative (DGI), which was formed in 2004 and is aimed at deciphering the genetic causes of type 2 diabetes. The collaboration brings together diverse expertise in diabetes and metabolic disease, human genetics, genomics, statistical analysis, and drug development.

"These discoveries are but a first step. To translate this study's provocative identification of diabetes-related genes into the invention of new medicines will require a global effort. We hope many will race to do so," said Mark Fishman, president of the Novartis Institutes for BioMedical Research. "We hope as well that others adopt this novel and effective mode of open collaboration between scientists and physicians, in business and academia, and dedicate work to our patients by making the data quickly and freely available to all."

Type 2 diabetes and related cardiovascular risk factors, including obesity, high blood pressure, and high cholesterol, are among the most common and significant public health challenges in the industrialized world. Their incidence continues to climb despite advances in biomedicine, highlighting the need for new insights into the disorders' root causes and novel strategies for prevention and treatment. Although type 2 diabetes clearly runs in families, suggesting the importance of inherited factors, its genetic origins remain largely unclear.

DGI is an international collaboration of the Broad Institute of MIT and Harvard, Lund University, and Novartis. Collaborators include scientists from the Jackson Heart Study and the University of Southern California. The Broad Institute team includes scientists from its partner institutions, which include Harvard Medical School, Massachusetts General Hospital, and Children's Hospital Boston.

Proteasome recognized as nuclear player on gene-transcription team

70652986 — Mon, 26 Mar 2007 06:26:37 -0400

One of the most common agents in the cytoplasm of the cell, the proteasome, also plays a widespread and critical role in transcription from inside the cell nucleus.

Pam Silver, Kathryn Auld, and their colleagues report in the March 17, 2006 Molecular Cell that the proteasome binds and critically regulates the transcription of some of the most highly expressed and important genes in the yeast genome, including those involved in lipid metabolism, mating behavior, and the making of ribosomal proteins.

"We found the proteasome to be very important in so many roles in yeast transcription that I cannot imagine it is not important in other organisms," Auld said.

Lab moves genomic testing into the clinic

70652986 — Mon, 26 Mar 2007 06:23:23 -0400

The earliest symptom of the inherited heart condition hypertrophic cardiomyopathy can be sudden death at a tragically young age. Harvard Medical School researchers discovered the first human gene underlying the disorder 15 years ago, but clinical genetic testing to identify those people at risk just became available last year.

About the same time, another genetic test emerged to detect the one in 10 lung cancers susceptible to certain new targeted drugs, within months of reports by two HMS teams that these drug-responsive tumor cells have mutations in a key signaling domain of their epidermal growth factor receptors (EGFRs).

Cancer link to 'protein promiscuity' being studied

50443248 — Fri, 20 Jul 2007 09:49:13 -0400

When found at abnormally high concentrations, two proteins implicated in many human cancers have the potential to spur indiscriminate biochemical signaling inside cells, chemists at Harvard University have found. Their finding may expand scientists' current understanding of oncogenesis - that cancer arises when an oncoprotein becomes overactive, ramping up the biochemical pathways that it normally activates - suggesting that an important additional mechanism could be the inappropriate activation of numerous secondary pathways.

Double trouble: Cells with duplicate genomes can trigger tumors

70652986 — Mon, 26 Mar 2007 05:40:58 -0400

So-called "double-value" cells are produced by random errors in cell division that occur with unknown frequency. The generation of these genetically unstable cells appears to be a "pathway for generating a tumor," says David Pellman, MD, a pediatric oncologist at Dana-Farber and at Children's Hospital Boston and an associate professor at Harvard Medical School. He is the senior author on a report in the Oct. 13, 2005 issue of Nature. Takeshi Fujiwara, PhD, and Madhavi Bandi of Dana-Farber are the paper's co-first authors.

The research was performed in experimental animals, but such "double-value" cells are seen in a variety of early human cancers and in a precancerous condition called Barrett's esophagus. In addition to the extra chromosomes, the "double value" or "tetraploid" cells also duplicate a cell structure called the centrosome that plays a role in maintaining a stable genome. The extra centrosomes may be at the root of the cancer- triggering process. Once the genetic instability sets in, tumors "evolve" by losing, gaining and rearranging chromosomes.

The new findings confirm a far-sighted notion of Theodor Boveri, a German scientist of the 19th century who was one of the discoverers that the chromosomes in the nucleus of the cell carry the material of heredity, or genes. In 1914, he published what Pellman calls an "amazingly accurate and prescient" treatise suggesting, among other things, that genetic instability was a cause of malignant tumors.

Surprising variations discovered in human genomes

70652986 — Mon, 26 Mar 2007 05:35:54 -0400

Researchers from Harvard Medical School and the University of Toronto in Canada looked at 55 healthy, unrelated men and women, and they discovered 255 regions with relatively large gains or losses in their DNA. "We were extraordinarily surprised to see that some people have so much more or less DNA," says Charles Lee, a geneticist and assistant professor at Harvard. "This is very exciting. It could explain differences in human nature, and help us identify people who are more prone to certain diseases." "This discovery may help us to better understand the nature of humanity," says Lee. To share their treasure, the Harvard-Toronto collaboration makes the details of their discovery available to the public in the Genome Variation Database (http://projects.tcag.ca/variation). A scientific report on the findings also appears in the September 2004 issue of Nature Genetics.

Scientists identify hundreds of worm genes that regulate fat storage

70652986 — Mon, 26 Mar 2007 05:28:29 -0400

Findings by Harvard researchers, published in the Jan. 16, 2003 issue of Nature, represent the first survey of an entire genome for all genes that regulate fat storage. The research team led by Gary Ruvkun, of the Massachusetts General Hospital Department of Molecular Biology, and postdoctoral fellow Kaveh Ashrafi identified about 400 genes encompassing a wide range of biochemical activities that control fat storage. These studies were conducted using the tiny roundworm Caenorhabditis elegans, an organism that shares many genes with humans and has helped researchers gain insights into diseases as diverse as cancer, diabetes, and Alzheimer's disease. Many of the fat regulatory genes identified in this study have counterparts in humans and other mammals. "This study is a major step in pinpointing fat regulators in the human genome," says Ruvkun, who is a professor of genetics at Harvard Medical School. "Of the estimated 30,000 human genes, our study highlights about 100 genes as likely to play key roles in regulation of fat levels."

Formin gene may explain a common cause of female infertility

70652986 — Mon, 26 Mar 2007 05:28:02 -0400

Harvard Medical School researchers Philip Leder and Benjamin Leader have discovered that oocytes from female mice without the formin gene Fmn2 cannot correctly position the metaphase I DNA-spindle. This produces daughter cells with an abnormal number of chromosomes, the leading cause of female infertility, birth defects, and embryo loss. Genes of the formin family, including Fmn2, are expressed in almost all organisms. The discovery may help explain recurrent pregnancy loss, a condition that affects millions of women throughout the world.

Harvard researchers complete genomic sequence of deadly malaria parasite

70652986 — Mon, 26 Mar 2007 05:23:30 -0400

Malaria is the world's most serious parasitic tropical disease and kills more people than any communicable disease except for tuberculosis. There is more human malaria in Africa today than at any time in history. P.falciparum, the most lethal form of the disease, accounts for the majority of infections, 200 to 300 million, resulting in 1 to 3 million deaths annually. One quarter of the world's population is at risk for infection. Now researchers are looking for clues to the mysteries that have made malaria impossible to defeat with drugs. Dyann Wirth, director of the Harvard Malaria Initiative and professor of immunology and infectious diseases at the Harvard School of Public Health, is author of two papers focusing on what has been learned from the genetic sequencing of P.Falciparum and how it can possibly be applied to public health. The papers appeared in the Oct. 3, 2002, issue of the journal Nature and the Oct. 4, 2002, issue of the journal Science.

The next big thing in mining the genome

70652986 — Mon, 26 Mar 2007 05:22:07 -0400

About 99.9 percent of the 3.1 billion base pairs in the human genome are the same from person to person. The remaining 0.1 percent of differences comprises more than 10 million common single-letter genetic variations (and many more rare variants) scattered through the genome. By the numbers, a comprehensive search for the multiple genetic contributions to prevalent conditions such as diabetes and Alzheimer's has loomed as a long, slow, and expensive prospect. Now, potentially simplifying the search, scientists say long blocks of DNA have traveled from one generation to the next with little genetic shuffling, according to a study published in Science in June 2002. These genome segments are called haplotype blocks.

Mustard shows backbone in its own defense

70652986 — Mon, 26 Mar 2007 05:20:26 -0400

Over the past few years, accumulated evidence from many scientists suggests that plants, animals, and insects share common elements in their innate skirmishes with potential pathogens. In the Feb. 28, 2002 issue of the journal Nature, plant scientists at Massachusetts General Hospital and Harvard and their colleagues have reported another striking similarity. The researchers identified the step-by-step process from the sentry guarding the cell perimeter to the deployment of the defensive immune mechanisms. The details from danger signal to action were worked out in isolated cells of the mustard Arabidopsis thaliana.