Sure, But Which Gene Helps Her Remember Everyone's Birthday?

Last week it was announced that, for the first time, the full genome of a woman had been sequenced:

http://www.eurekalert.org/pub_releases/2008-05/nofs-lss052708.php

The lucky gal was Dr. Marjolein Kriek, a clinical geneticist at Leiden University Medical Centre in the Netherlands, where the study was undertaken. This was not only the first sequence of a woman, but also the first of a European.

The sequencing had taken six months, reading over 22 billion base pairs (the "letters" of DNA for you non-science types out there), but had been run in-between other experiments. If it had been run straight through, it would have taken only 10 weeks. Typical. Once again women get second billing! Go on, you female lab rats! Throw down your test tubes and burn your bras! I'll only gawk a little.

The first human sequence, as you may remember, was completed in 2001 using the combined DNA of several people. The next was that of Jim Watson, co-discoverer of the DNA double-helix structure. "Gene hunter" Craig Ventor was next. The final two were of Yoruba African men (I didn't know about those two, but now I'm curious).

In the words of the principal scientist of the study (as quoted in the article), "So it was time, after sequencing four males, to balance the genders a bit”. He smiles: “And after Watson we also felt that it was okay to do Kriek”.

Get it? Watson and Crick? Discoverers of the structure of DNA? Ha ha! Ha. ha. (sigh). Scientist humor….

Now that they have sequenced the X chromosomes of a female, the researchers say they are better able to study X chromosome variability.

That's well and good. But what I'd really like to know is which genes control that desire and ability of women to schedule everything. Or to coordinate their blouse with teal pumps. Or how to have a conversation on their tiny cell phone while simultaneously wiping a child's runny nose, stopping another child from climbing the bookcase, and writing up a report for their high-pressure career.

Yeah, that's right you sexy Dutch chicks, I've got your number (or at least the number of base pairs), and I've got a little Jean Gnome for you to "sequence". Giggity giggity.


Image altered from HERE.

Ancient Romans Had Crabs, But They Never Knew It

In 1997, a couple of zoologists were visiting the remains of Trajan's Forum in middle of Rome. They turned over a rock, and there, looking up at them, was an unassuming freshwater crab. They soon realized they had discovered a new species, Potamon fluviatile, the only freshwater crab species known to inhabit a large city:

http://www.physorg.com/news100094217.html

"So what?" you ask. Stupid crabs. All googly-eyed and leg-y. They'll pinch ya. Throw that puppy in a pot, boil it alive, and serve it up with some melted butter!

But the researchers didn't eat the crabs. They studied them, genetically. What they discovered is not just that Rome had crabs, but that those crabs had been there a very, very long time. So long, in fact, they pre-dated the forum, which was built in 112 AD, and even predated Rome itself (founded in 753 BC), all the way back about 3,000 years ago, to the time of the ancient Etruscans. The little buggers had been living in ancient Etruscan canals that ran under the forum and joined up with the ancient Roman sewage system.

What's more, the crabs are genetically unrelated to other Italian crabs. In fact, they are most closely related to Greek freshwater crabs, probably introduced all those millennia ago by Greek traders or colonists (BEFORE the time of Alexander the Great, Aristotle, Plato, or Socrates). Except that, without natural predators, the Roman crabs (which are about 12 cm, or 4.8 inches, wide) had evolved to be over twice the size of their Greek counterparts (which were only 5 cm, or about 2 inches, wide). There are now an estimated 1000 crabs down there.

So as the Etruscan culture fell and was replaced by the land of Romulus and Remus (no, I'm not talking about Star Trek Romulons, you geek!), through the rise of the Roman Republic, the rule of the Roman Empire, the fall of Rome to Germanic Barbarians, the rule of the Byzantines, the rise and fall of the Papal States, the Kingdom of Italy, through Italian Fascism and Mussolini, World War II, and the post-war reconstruction, no one knew that the crabs were down there, clicking away in the dark, feeding on algae and snails, as well as scraps of food and detritus that washed down from the city above. Yum!

I imagine that, occasionally, one of the little hard-shelled critters skittered up to the surface to take a look around and see what century it was, then retreated back down to crab paradise to report on the latest stupid human tricks:

Crab #1: "Hey, you wouldn't believe what those humans are up to these days. Some dude named Julius just got stabbed to death by a mob of his own homies."

Crab #2: "Cool. Did you bring back any scraps? I'm hungry."

Maybe, over those thousands of years, some Roman once in a while turned over a rock and found one of these little crustaceans staring up at them. The Roman probably thought, "Hey, free crab! Hail Caesar!" and boiled it alive for dinner. Mmmmm, with melted butter.....

Save Your Data On Bacteria

I worry about stupid things, sometimes. Not practical things, like how I’m going to potty train my toddlers or where I can buy an affordable steam cleaner, but about the big, giant things I could probably never do anything about. Those “oh my god” sorts of problems that most people shake their heads about but don’t think on any further because they’re sensible enough to know they couldn’t possible do anything about it, like forging peace in the Middle East, controlling AIDS in central Africa, and stopping the polar ice caps from melting. You know, the “little things.”

For instance, I worry about what’s going to happen to all the monumental loads of data and information the world generates every day. Is it safe? Where does it all go? How can we insure it never gets lost or corrupted? I absolutely loathe the idea that someone would spend valuable time collecting information and recording it, only to lose it. I guess that’s what makes me a good lab rat. And, yes, I have multiple backups for all my data, right down to a spreadsheet for my VCR and DVD movies at home. What? You don’t have such a spreadsheet? How else am I to remember that I have a VCR tape copy of Highlander? (“There can be only one!”)

Previously I posted about how a state official in Alaska had accidentally deleted 800,000 refund payment files, then accidentally deleted the backup disc. A second backup had been corrupted. This is exactly the sort of thing that worries me. Luckily they had the original paper documents, and after months of overtime by employees they re-entered all the data.

Once upon a time all we had was papyrus and velum, then we invented paper. There are still a few of these ancient documents around, preserved by desert conditions and now tucked away in museums, but think of all the documents that were lost over thousands of years! Where would civilization be, now, if they had been safeguarded better? Essentially, most of our modern information is still on paper, paper that for the most part is made with cheaper and less durable ingredients, I might add. Now we have digitized storage media, but the accident in Alaska shows how unreliable that is, even in the short term. Hundreds of years from now, do you think we’ll be able to retrieve that information? Do you think we’ll even have the same technology lying around to do it?

Well, now some Japanese researchers may have found a way to help alleviate my worry. They have found a reliable method to store data on the DNA code of living bacteria, which could protect that data for hundreds or even thousands of years!

Story: http://www.physorg.com/news98542190.html

Scholarly article: http://pubs.acs.org/cgi-bin/sample.cgi/bipret/2007/23/i02/pdf/bp060261y.pdf

That’s right, save data in the DNA of living bacteria in a manner similar to storing data on computer discs. And you thought bacteria was only good for making beer and cheese!

For you non-science types, DNA is made up of four components, called nucleotides, which pair up in specific combinations, or genes, to code for the production of all the proteins that make up cells, organs, and, eventually, YOU, and every other living thing on earth. For decades, molecular biologists have found increasingly clever ways of identifying those codes, manipulating them, synthesizing them, and inserting them into DNA sequences. Left alone, these genetic sequences take thousands, or even millions, of years to change due to random mutations as they are inherited from generation to generation.

Dr. Masaru Tomita and his colleagues have found a way to store data by synthesizing their own genetic sequences. Each combination of the nucleotides in these sequences corresponds to specific binary codes. These binary codes can then be matched with specific letters or numbers. Those sequences were then inserted into the DNA of living bacteria (of the species Bacillus subtilis).

They successfully inserted, then later retrieved, the codes for the phrase "E=mc^2 1905!", referring to Albert Einstein’s theory of relativity and the year he published his Nobel-prize-winning theorem. Because they inserted the code in four different locations in the DNA, mutation in one copy can be corrected by the other three copies. Computer simulations, based on the predicted rate of mutation, suggest the code is secure for hundreds to thousands of years.

Though the amount that can be stored in the bacteria is limited by the genome size, and the person who eventually reads the data would need to know the code that deciphers the nucleotide combinations and matches them with numbers and letters, Tomita’s technique essentially safeguards the information far, far into the unseen future. According to the CNN story: "Many people never even thought about storing data for thousands of years," Tomita said. "This may sound like a dream. But we're thinking hundreds of millions of years."

Now THAT would solve my insane worries. All we have to do is figure out how to make a "bacterial disc drive" to store my data for the next thousand years. Then where would I store it? The fridge? -- “Wait, Honey! Don’t throw out that rancid milk! Those bacteria have my movie database saved on them!”

Doggy DNA And The Benefits Of Being Small

I like small people. I should, since I’m pretty small, and my lovely wife is the same height.

Think of all the benefits of being small. We fit better in compact cars. You can fit more of us on a sofa, bed, trampoline, or any other small space. We aren’t as heavy or bulky, so we make better astronauts, airline attendants, and horse jockeys. Airline and theater seats are more accommodating. We tend to eat less and talk softer. We look smashing when costumed as leprechauns, Yoda, or E.T. We don’t need as much clothing in square footage to cover our bodies, so clothes are cheaper. Finally, and perhaps most importantly, it’s easier for us to do the limbo.

Oh, sure, there are drawbacks as well, like reaching high shelves, changing light bulbs, or peeking over fences to spy on neighbors, but that’s what ladders are for. And maybe there are “heightist” people out there who discriminate against us. But then, do I really want to hang out with those tall folk? Gravity affects them more, and I don’t want to be slowed down by their gravity-dragging bulk.

Yes, it’s not so bad being small. In fact, maybe there should be MORE of us around. Do you think we could genetically engineer people to be born small? Eugenics, of a sort?

Well now we’ve taken a step toward making that wonderful world a reality, thanks to some miniature dogs and their geneticist owners and other researchers:

http://www.physorg.com/news95001402.html

As published in the recent issue of Science magazine (see HERE for the article abstract), researchers found that a regulatory sequence for a gene for insulin-like growth factor 1 (IGF1) is found only in dog breeds under 20 pounds. Larger dogs had the gene, but not the regulatory sequence. This gene is found on doggy chromosome 15. The study started with some small Portuguese water dogs owned by one of the authors, then “expanded the genetic analysis to 3,241 dogs from 143 breeds, ranging from small ones like bichon frise, Chihuahua, Maltese, Pomeranian, toy poodle, pug and Pekingese to large breeds such as Saint Bernard, Newfoundland, mastiff, Great Dane, Irish wolfhound, and standard poodle.” Said the authors (according to the PhysOrg.com article), “All dogs under 20 pounds have this – all of them. That's extraordinary." With one curious exception (Rottweilers), none of the larger breeds had the haplotype.

The researchers will next be inserting this haplotype (gene plus regulatory sequence) into mice to study the effect.

Okay, so when can we start transforming our human embryos with this doggy DNA? Yes, as in genetic engineering of humans. I want a world of little folk! But this might have some unintended side effects. Can you imagine a world full of little people who get yappy and pee on the rug at the drop of a hat?

Sleep Problems, Part II

I'm not a "morning person." Even on the best of work days, getting me out of bed takes a force of willpower comparable to running into a burning building. I've always been that way, even as a boy. I would stumble out of my bedroom in the mornings, skipping breakfast so I could get an extra ten minutes on the pillow, running late to catch the school bus at the last possible minute. I doubt I got many A's in the first-period classes. Still, no matter how much caffeine I pump into myself, I don't *really* wake up until about 10:30. I've also always been a "night owl," staying up 'til midnight or later. Unless I'm sick or totally exhausted (which happens more often now that I have kids), I simply can't fall asleep before 11PM, no matter how hard I try. It's my natural rhythm. Being sleep-deprived with kids has only heightened my morning pain. I'm certain when I finally croak it's going to be after trying to get up one early morning.

There have been times in my life when I've tried to change. Our society isn't very tolerant of night-owls / late-sleepers like me, viewing us as lazy for sleeping in, and as disorganized or party-crazy for staying up at night, no matter how much we do during the day. I had an agricultural science job for a little over a month, many years ago, where I had to get up while it was still dark, commute about 45 minutes, and report for work at the break of dawn. I tried very, very hard to change, going to bed by around 9:30PM whether I was tired or not, taking cold showers in the morning to wake up, and quaffing a higher-than-usual volume of caffeine. Have you ever seen "The Return of the Living Dead", where rag-dressed zombies shamble after hapless yet incredibly slow victims, arms outstretched and muttering, "Brains…."? Now take one of those zombies and put them in a field full of strawberries and fruit trees. That was me.

Can you tell I'm having trouble adjusting to the new time change?

In an interesting coincidence, many years back I landed in a doctoral program studying circadian rhythms of insects (a "circadian rhythm" is the scientific term for natural day-night cycles for animal behavior and physiology). To do this, I dissected about a zillion fruit flies under a dissecting microscope, pulling them apart with very fine forceps and teasing out their organs (Yes, the flies were usually alive when I did this. There is sure to be some sort of karmic retribution waiting for me. Any day now a thick swarm of fruit flies will descend on me and eat me like a gigantic banana, their natural prey). Anyhow, part of my studies was to examine the role of a gene called period (named for its periodic cycle of expression through the course of a day). This was also the only job I've ever had where I could choose my own hours – not unusual for academics. I usually wandered in around 10AM, worked until around 5PM, then came back in the late evenings for two or three more hours of work. I loved it (the work, that is. I can't say the same about the manic scientist who ran the lab and was my doctoral advisor), but I couldn't make a living on the meager earnings of a grad student and had to get a "real job."

Now it all comes full circle. Like so many other conditions related to our health and behavior, science has now linked my "night owl" circadian rhythm to my genes, even when it comes to effects of sleep deprivation (such as children crying in the middle of the night for, oh, two and half years). Molecular biologists and psychologists have been able to link human circadian rhythm to genes in humans which are analogues of the genes I studied in fruit flies, including period. One, in humans, is called period3, which comes in a "long" form and a "short" form, and has been shown to play a role in determining if humans are "larks" or "owls". The study to be published in the next issue of Current Biology demonstrates the role of this gene in the effects of sleep deprivation:

Story: http://www.physorg.com/news92670935.html

The journal abstract, for you science-types: HERE

Apparently, my period3 is "long" (No, I'm not menstruating). According to the article, "individuals with the longer variant of the gene performed very poorly on tests for attention and working memory [in the early morning hours]. Cognitive Psychologist Professor John Groeger, says: 'the early morning performance problems of those with the long variant have important implications for safety and efficiency at work.'" Those with the short form of the gene performed well.

So there ya go. I haven't been tested, but I'll bet I'm "genetically challenged," at least in the early morning. So if I come to work looking dreary-eyed and you try to bug me, I'm going to hold up may hand and snarl, "Talk to the genes!" then continue on my way to my morning dose of caffeine.

Now get some sleep!

Suicide Genes And My Conspiratorial Mind

There are some DNA sequences so dangerous that they don't exist. Call them "suicide genes":

http://email.newscientist.com/cgi-bin1/DM/y/n1cA0MXCX60XrF0DdEM0E3

No, I'm not talking about some genetic propensity that, if you have these genes, will make you want to take a swan dive off the Grand Canyon. I'm talking about genes that are so lethal that no organism can survive if they have them. Most likely their protein products bound some essential part of cellular mechanism. A researcher at Boise State University has created a computer program to calculate all the possible nucleotide sequences possible in the human genome. So far, he has found 86 sequences of 11 nucleotides in length which have never been reported. The thought is that random mutation over the eons may have created these genes, but because they killed the developing embryo before birth, the mutation didn't "stick" in our species. Of course, the absence of these genes from the modern human genome may not mean the developing embryos with these genes died before birth, it just means the individuals didn't live to reproduction. How do we know, I ask? Maybe the "suicide genes" just make someone so butt ugly no one would mate with them! I could think of one or two individuals these researchers forgot to screen.

Now, calling them "suicide genes" is really very hypothetical. The only way to tell if they would cause a cell to die is to transfect the sequences into the DNA of living cells or organisms (humans?), which he hasn't done to my knowledge. But should we? For that matter, I ask, is it _ethical_ to explore this issue?

The Department of Defense has gotten involved by funding the research (a million bucks, no less). They say it is "to develop a DNA 'safety tag' that could be added to voluntary DNA reference samples in criminal cases to distinguish them from forensic samples." That would be nice, but wouldn't careful labeling of tubes be sufficient?

No, my conspiratorial little mind thinks they have other plans. Since when is the DoD interested in altruism? Imagine if you could somehow insert these "suicide genes" into living humans. Modern medicine is closing in on viral therapies which could do the trick. Just inhale some viruses that can transfect your cells. Better yet, attach sequences to the suicide genes that activate them only under certain conditions. Murder on command!

Do I hear a mad scientist in the wings? Mwa ha ha ha….

Sunlight, DNA Mutation, And My Face Melting Off

Man, I hate sunburns. My paternal grandmother was deathly afraid of sun damage, skin cancer in particular, so much so that she often carried an umbrella (she called it a parasol) outside with her, even just to sit in the yard for a few minutes. Interestingly, her fears came true. She developed a few skin polyps on her nose in her last years, despite all the umbrella-toting.

My grandmother's umbrella came screaming back to my consciousness a few years ago when I burned my face off. I went downhill skiing the first (and only) time – and didn't bring sunblock. "No problem," I thought, "I'll just be here a couple hours." Oh, woe is me! How very naïve I was of the dangers of high-altitude UV radiation and snow reflection! I was there for several hours more than I thought I would be, enjoying a newfound excitement of speeding down snowy hillsides, avoiding other skiers, and tumbling onto my butt and through the air in exotic poses of flailing arms, skis, and ski poles. Great fun. I'll do it again some day.

The next morning I noticed a strange moisture seeping out of my cheeks. It was clear liquid. Was I sweating? I didn't know what to think of it, so I taped some gauze on my cheek and went to work anyhow. Once at work, I busied myself as usual. After an hour or so I noticed the gauze was soaked, so I went to the bathroom to re-evaluate my strange condition. When I took the tape off, part of my cheek went with it! And, boy, did the liquid start coming out! I was positively dripping!

Long story short, I rushed to a medical clinic (and sat for hours in their stupid waiting room) and found out I had a second-degree sunburn. The top layer of skin hadn't bothered turning red first, it just said, "Goodbye cruel sunlit world" and died. My pasty face melted off over the course of about a week. "Peeled off" would be too kind of a phrase. I didn't have enough leave time left at work, so I had to work during that time, my face covered with bandages. Not a good situation. Needless to say, I wasn't very popular with coworkers. The thought running through my mind that whole time was, "Am I going to get skin cancer from this rather severe amount of UV radiation?"

Well, researchers at Ohio State University and their colleagues in Germany have now been able to directly observe UV radiation mutating DNA:

http://www.physorg.com/news89563086.html

It's reported in the latest addition of _Science_: http://www.sciencemag.org/cgi/content/abstract/315/5812/625

It's been known for a long time that exposure to UV light (like in sunlight) can cause skin cancer because the energy level from the intense UV radiation causes mutations in the DNA, leading to uncontrolled cell growth (cancer) or cell death (in the case of a sunburn or, more extreme, your friggin' face melting off!). Femptosecond transient absorption spectroscopy is a very new method for visualizing extremely fast reactions at the molecular level. In short, this method uses lasers to excite molecules and an extremely fast light pulse and detector are used to look at changes in the energy levels of the molecule changed by the laser. Using this method, the researchers directly observed how UV radiation caused the formation of two chemical bonds between thymine molecules in the DNA structure. This was a pretty artificial test sample (artificial thymine-only DNA), and not in actual cells, and didn't involve all the chemical pathways involved with sunburn, but it DOES show for the first time actual DNA mutation from UV radiation, which is a huge step in understanding such mutations.

The authors probably don't go so far, but I'm wondering, could similar, non-deadly mutations happen that could lead to genetic changes in the morphology of bacteria or simple-celled organisms, perhaps even changes that could lead to development of new species adaptations, leading toward evolution?

Anyhow, this all makes me even more concerned about skin cancer and my little bout with my skiing incident!