4. The Puzzle of Inheritence

Archive of Past Articles for Chapter 4

2010 Mar 11. Disease Cause Is Pinpointed With Genome. By Nicholas Wade, New York Times. Excerpt: Two research teams have independently decoded the entire genome of patients to find the exact genetic cause of their diseases....
In the decade since the first full genetic code of a human was sequenced for some $500 million, less than a dozen genomes had been decoded, all of healthy people.
Geneticists said the new research showed it was now possible to sequence the entire genome of a patient at reasonable cost and with sufficient accuracy to be of practical use to medical researchers....
In one case, Richard A. Gibbs of the Baylor College of Medicine sequenced the whole genome of his colleague Dr. James R. Lupski, a prominent medical geneticist who has a nerve disease, Charcot-Marie-Tooth neuropathy....

2010 Feb 17. Scientists Decode Genomes of Five Africans, Including Archbishop Tutu. By Nicholas Wade, NY Times. Excerpt: The complete genomes of five southern Africans have been decoded, almost doubling the number of published human DNA sequences. The Africans include four Bushmen hunter-gatherers, known as !Gubi, G/aq’o, D#kgao and !Ai, the odd symbols representing different clicking sounds in Bushmen languages. The fifth person, a Bantu, is none other than Archbishop Desmond Tutu.
...African genomes are of particular interest for understanding human genetic history because they have more variation in their DNA than other populations. Everyone outside Africa is descended from a small group that left some 50,000 years ago, carrying away only a small sample of the available genetic diversity....
...Geneticists are interested in variations in the human DNA sequence because these underlie human diversity, including susceptibility to disease. The Pennsylvania team found 1.3 million novel DNA variants in its five Africans, and some 13,000 new changes in those parts of the DNA that specify proteins, the working parts of living human cells....

2009 March 3. A Call for Resilient Farms in Warming World. By Andrew C. Revkin, The NY Times. Excerpt: In the icy gloom of Norway’s Arctic archipelago, scientists gathered last week to celebrate the first anniversary of the Svalbard Global Seed Vault, an archive of the world’s agricultural genetic diversity carved into the frigid earth. I got a “post card” over the weekend from one participant, Nina Fedoroff, the science and technology adviser to the secretary of state and to administrator of the United States Agency for International Development.
Dr. Fedoroff is a longstanding proponent of probing and exploiting genes to make crops and livestock more productive and less vulnerable to pests and climate extremes. This puts her at odds with some environmentalists and European governments.
Her full dispatch...is focused on the importance of preserving and exploiting genetic diversity as a way to sustain food production in the face of both growing human populations and appetites (prosperity still tends to boost peoples’ appetite for meat) and rising dangers from warming driven by accumulating greenhouse gases....

2009 February 29. A worldwide pollutant may cause gene loss. By Niladri Basu, Environmental Health News. Excerpt: A new study suggests that long term exposure to a common water pollutant reduced the genetic diversity of the midge - a common water insect.
Aquatic insects are the foundation of healthy waterways. Other insects, invertebrates and fish depend on the tiny creatures for food. A loss of their genetics is a loss for ecosystem diversity.
The pollutant, called tributyltin (TBT), is a widely used pesticide. While TBT affected the growth, survival and reproduction of the midge insect, the greatest effects were found in the genes. TBT-exposed insects lost gene diversity two times greater than non-exposed insects.
The study provides direct evidence from the lab that pollution may cause genetic loss in nature....
Genetic diversity is the number of different kinds of genetic characteristics in a species. Genes govern an individual's characteristics -- whether external appearances or internal functions. Diversity ensures that a population has a large number of gene variations spread among individuals.
...Before its recent worldwide ban, TBT was used extensively in marine paints to keep barnacles and other marine creatures from growing on ship hulls. In the environment, TBT does not break down and it builds up in food chains. Because of its longevity and widespread use, it is no surprise that TBT pollutes harbors, waterways and animals all over the world....

2008 July/August. Tracing Evolution in Genes. By Kathleen M. Wong, ScienceMatters@Berkeley. Excerpt: How do humans differ from chimpanzees? ...we're taller, less hairy, and-a point no one fails to mention-far brainier than our closest primate relatives.
All of these differences and more have emerged over the past five million years, when the common ancestor of both species reached an evolutionary fork in the road. How early hominids came to walk the savannah, while early chimpanzees returned to the forests, has fascinated professional scientists and armchair anthropologists alike.
The best way to answer those questions, according to Rasmus Nielsen, is to study our respective genomes. "Evolutionary biology is an historical science," says Nielsen, a Berkeley professor of integrative biology. "But in the absence of a time machine, we can't really go back and show exactly why certain evolutionary events occurred. All we have to work with is what we observe today. So we look at the DNA to see the evidence for past Darwinian selection."
Nielsen uses the power of statistics and computing to compare the DNA of different species or populations. By identifying which sets of genes have changed, or mutated, he can describe how ancestral populations diverged step by tiny genetic step. His work not only recasts the story of human evolution but promises to uncover the genetic roots of many diseases...

2008 May. Distant Relatives, Common Genes. By Kathleen M. Wong, ScienceMatters@Berkeley. Excerpt: Glance through any family's photo album, and you're likely to home in on a few outstanding ancestral traits. The shape of a nose or the arch of an eyebrow can be passed down for generation after generation.
Biologists have long studied commonalities such as these to infer ancestral relationships between animals. But the more distant the relationship, such as between humans and sponges, the trickier it is to establish connections through simple comparisons of anatomy.
Dan Rokhsar, a Berkeley professor of both physics and molecular and cellular biology, and a faculty scientist at the Department of Energy's Joint Genome Institute, is sidestepping this problem via a different aspect of inheritance: genes. Genes shared by distantly related animals are likely to have originated in their last common ancestor. So by sequencing and comparing the genomes of creatures ranging from sea anemones to sea squirts, limpets to pufferfish, Rokhsar and his research team hope to reconstruct characteristics of the great-great grandparents to all animals.
"We're interested in that transition from being a unicellular organism to being multicellular-when it happened and how it happened," Rokhsar says…
Recently, the skyrocketing price of petroleum and the threat of global climate change have turned Rokhsar's attention toward greener subjects: plants…
"The cellulose and lignin in plant walls is where all of the carbon goes from photosynthesis. That's the carbon we want to convert to fuel. How do they do it? One way to find an answer is to look at genomes," Rokhsar says.
He is now working to sequence the genome of switchgrass, a native plant and strong candidate to produce biofuel…
"We need to collapse the 5,000 years it took to breed maize into an edible plant into 10 years for switchgrass, because we don't have a lot of time to develop renewable fuels," Rokhsar says. "And we'll need to do this sustainably and as a solution for the long term."

2008 April 22. Expressing Our Individuality, the Way E. Coli Do. By CARL ZIMMER, The NY Times. Excerpt: We humans differ from one another in too many ways to count...Scientists have only a rough understanding of how this diversity arises… We put a far bigger premium on nature than nurture when it comes to our individuality. That’s one reason why reproductive cloning inspires so much horror. If genes equal identity, then a person carrying someone else’s DNA has no distinct self. But there’s a deep flaw in this way of thinking, one that blinds us to how biology — human or otherwise — really works. A good counterexample is E. coli, a species of bacteria that lives harmlessly in every person’s gut by the billions. A typical E. coli contains about 4,000 genes (we have about 20,000). Feeding on sugar, the microbe grows till it is ready to split in two. It makes two copies of its genome, almost always managing to produce perfect copies of the original. The single microbe splits in two, and each new E. coli receives one of the identical genomes. These two bacteria are, in other words, clones...E. coli expresses its individuality in many other ways, as well…These quirks of E. coli’s personality can mean the difference between life and death for the bacteria. In times of stress, some members of a colony respond by building thousands of toxin molecules and then burst open, killing off the unrelated E. coli around them. Their fellow clones survive, though, and thrive without the competition.
The key to understanding E. coli’s fingerprints is to recognize that the bacteria are not simple machines. Unlike wires and transistors, E. coli’s molecules are floppy, twitchy and unpredictable. In an electronic device, like a computer or a radio, electrons stream in a steady flow through the machine’s circuits, but the molecules in E. coli jostle and wander. When E. coli begins using a gene to make a protein, it does not produce a smoothly increasing supply. It spurts out the proteins in fits and starts. One clone may produce half a dozen copies of a protein in an hour, while a clone right next to it produces none.
Other studies suggest that the unpredictable noisiness in E. coli’s cellular machinery is also responsible for persistence, hairy coats, selfless suicide and vulnerability to viruses. The big question for many scientists is why E. coli has evolved so that noise can produce such drastic changes in its biology…
Identical genes can also behave differently in our cells because some of our DNA is capped by carbon and hydrogen atoms called methyl groups. Methyl groups can control whether genes make proteins or remain silent. In humans (as well as in other organisms like E. coli), methyl groups sometimes fall off of DNA or become attached to new spots. Pure chance may be responsible for changing some methyl groups; nutrients and toxins may change others.
…At the very least, E. coli’s individuality should be a warning to those who would put human nature down to any sort of simple genetic determinism. Living things are more than just programs run by genetic software. Even in minuscule microbes, the same genes and the same genetic network can lead to different fates.

2008 March 4. Gene Map Becomes a Luxury Item. by Amy Harmon. The New York Times. Excerpt: Dan Stoicescu, 56, a biotechnology entrepreneur who retired two years ago after selling his company, became the second person in the world to buy the full sequence of his own genetic code paying $350,000 price tag. Scientists have so far unraveled only a handful of complete human genomes, all financed by governments, foundations and corporations in the name of medical research.
But while money may buy a full readout of the six billion chemical units in an individual’s genome, biologists say the superrich will have to wait like everyone else to learn how the small variations in their sequence influence appearance, behavior, abilities, disease susceptibility and other traits.
Biologists have mixed feelings about the emergence of the genome as a luxury item. Some worry that what they have dubbed “genomic elitism” could sour the public on genetic research that has long promised better, individualized health care for all. But others see the boutique genome as something like a $20 million tourist voyage to space — a necessary rite of passage for technology that may soon be within the grasp of the rest of us.
Scientists say they need tens of thousands of genome sequences to be made publicly available to begin to make sense of human variation.
Mr. Stoicescu, who wants to create an open database of genomic information seeded with his own sequence, hopes others will soon join him.

2008 February. Statistical Challenges in Genomics. by Kathleen M. Wong, ScienceMatters@Berkeley ...Called a DNA microarray, it is a miniature laboratory on a chip. In a single experiment it can deliver a detailed snapshot of the thousands of genes and proteins interacting in an organism, whether bacterium or human.For biologists, DNA microarrays have been boon and curse alike. Researchers routinely use these assays to monitor gene expression patterns in cells from cancer patients, with the aim of deriving better diagnosis and treatment strategies for the disease. They can now obtain unprecedented insights into the activities of genes and cells with a minimum of experimental effort. At the same time, they are struggling to make sense of the tidal wave of data that ensues. "Each microarray experiment yields thousands and thousands of measurements for just one person," says Sandrine Dudoit, a Berkeley professor of Biostatistics and Statistics. "Microarrays and other high-throughput biological assays are raising challenging statistical design and analysis questions and are a driving force for our discipline. The scale and complexity of the data are unprecedented and far greater than traditional methods allow you to handle." ...Dudoit specializes in developing statistical and computational methods to analyze and comprehend the mind-bogglingly large and intricate datasets generated by high-throughput biotechnologies such as DNA microarrays. ...She develops statistical methods to uncover relationships among a patient's entire genome; demographic and environmental variables such as age, sex, ethnicity, and diet; and medical outcomes such as survival prognosis and response to treatment. ...With a next generation of DNA sequencing machines entering the scene, we are facing new and even greater statistical and computational challenges," Dudoit says. "You feel like your work really matters; it's being applied immediately, with the goal of elucidating fundamental scientific questions and improving public health."

2008 February. Gene escapes to weeds from engineered canola. Union of Concerned Scientists newlstter. A recent study found that canola plants in Quebec, Canada, that were genetically engineered for herbicide resistance have interbred with a weed called wild mustard, producing hybrid plants that are resistant to the herbicide glyphosate. The herbicide-resistance gene persisted over five generations and spread from the hybrids into the mustard weeds, in spite of the fact that no herbicide was applied to the area. The event is significant for two reasons. One, it is the first known escape of a gene from a commercialized genetically engineered crop into a weed. Two, because canola is a major crop, covering an estimated two million acres across Canada, it is likely that gene escape has occurred at multiple sites in addition to the few that were monitored. The event echoes the escape of a gene for glyphosate resistance from field trials of bentgrass into wild relatives (see our previous story). Inadequate confinement of engineered crops may harm ecosystems in some circumstances and may hasten the development of herbicide-resistant weeds. Read the abstract describing the study in the scientific journal Molecular Ecology.

January 2008. The Copy Machine of the Cell
by Kathleen M. Wong. Excerpt: There comes a
time in many a cell's life when it feels the need to reproduce. But
before it can split into two, it must fashion a second set of genetic instructions to pass on to the new cell. When Berkeley professor of biochemistry and molecular biology Mike Botchan first began studying chromosome copying, basic questions about the process remained unknown. He wanted to understand how and where DNA replication began. Over the past three decades, Botchan has been instrumental in piecing together the story of what he calls "the elaborate dance of replication." Botchan began by studying viruses, the simplest of all life forms. These microbes contain relatively few genes in their chromosome, borrowing much of the machinery needed to duplicate their own DNA from host cells. ...To decipher the string of events required to start replication, Botchan mapped the initiation site-a place on a chromosome where replication begins-in a virus. He found that a certain DNA sequence attracts a virus protein involved in replication initiation. Only then can the virus helicase, which unwinds and separates the strands of DNA, bind to the chromosome and start unraveling DNA....
But do more complex organisms, such as insects and humans, copy their DNA in a similar fashion? To find out, Botchan studied a case of unchecked DNA replication in fruit fly embryos. The cells that go on to form the fly's eggshell duplicate certain sections of their DNA with astonishing rapidity, initiating replication at many sites at
once. In these cells, Botchan found and characterized a complex of proteins that finds the initiation site and prepares the chromosome so that a core replication machine can be assembled there. The core replication machine includes a six-protein complex used at all DNA replication sites. Several of these proteins form a pinwheel structure that encircles DNA, while another links to the polymerase enzyme that "reads" the sequence. In cells actively copying their
DNA, all of these proteins are located right on top of one another.
...Botchan's work, along with research by Berkeley biologists Eva
Nogales and James Berger, helps prove that DNA replication has
changed very little across evolution. "All three kingdoms of life
share a basic core machinery that assembles on DNA and prepares it for unwinding," Botchan says. Organisms ranging from E. coli to fruit flies, they find, have nearly identical chromosome copying methods, cementing the relationship of all life forms back to that first ancestral cell.

Archive of Past Articles for Chapter 4

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