Public and scientific understandings of genes

Via  Lena Groeger, writing at Scienceline:

An Austrian monk sits alone with his garden pea plants, recording if they’re yellow, green, round or wrinkly. He starts noticing simple patterns in how various traits appear in each generation: a yellow parent often produces yellow offspring, but two yellow parents can produce green offspring, and yellowish-green offspring simply don’t exist. From his observations he concludes that heritable properties are distinct units independently passed from parent to offspring—units that, many years after his death, will be called “genes.”

The seminal ideas of the monk Gregor Mendel fundamentally changed how scientists thought about inheritance. These concepts still provide the foundation for genetics taught in school textbooks, presented in newspaper articles and understood by the general public. But it may be time to move beyond Mendel’s valuable, but rather simplistic ideas. Research in genetics and developmental biology is complicating the typical notion of genes.

Currently, the public views genes primarily as self-contained packets of information that come from parents and are distinct from the environment. “The popular notion of the gene is an attractive idea—it’s so magical,” said Mark Blumberg, a developmental biologist at the University of Iowa in Iowa City. But it ignores the growing scientific understanding of how genes and local environments interplay, he said.

With the rise of molecular biology in the 1930s and genomics (the study of entire genomes) in the 1970s, scientists have developed a much more dynamic and complex picture of this interplay. The simplistic notion of the gene has been replaced with gene-environment interactions and developmental influences—nature and nurture as completely intertwined.

But the public hasn’t quite kept up. There remains a “huge chasm” between the way scientists understand genetics and the way the public understands it, said David Shenk, an author who has written extensively on genetics and intelligence. In his recent book The Genius in All of Us, Shenk explains that the public still thinks of genes as blueprints, providing precise instructions for each individual. Newspaper headlines touting “the gene for X” only perpetuate the blueprint metaphor.

“The elegant simplicity of the idea is so powerful,” said Shenk. Unfortunately, it is also false. The blueprint metaphor is fundamentally deceptive, he said, and “leads people to believe that any difference they see can be tied back to specific genes.”

Instead, Shenk advocates the metaphor of a giant mixing board, in which genes are a multitude of knobs and switches that get turned on and off depending on various factors in their environment. Interaction is key, though it goes against how most people see genetics: the classic, but inaccurate, dichotomies of nature versus nurture, innate versus acquired and genes versus environment.

Belief in those dichotomies is hard to eliminate because people tend to understand genetics through the two separate “tracks” of genes and the environment, according to speech communication expert Celeste Condit from the University of Georgia in Athens. Condit suggests that, whenever possible, explanations of genetics—by scientists, authors, journalists, or doctors—should draw connections between the two tracks, effectively merging them into one. “We need to link up the gene and environment tracks,” she said, “so that [people] can’t think of one without thinking of the other.”

A new (which is to say very old, but recently discovered) human ancestor?

Ewen Callaway writing in Nature News:

The ice-age world is starting to look cosmopolitan. While Neanderthals held sway in Europe and modern humans were beginning to populate the globe, another ancient human relative lived in Asia, according to a genome sequence recovered from a finger bone in a cave in southern Siberia. A comparative analysis of the genome with those of modern humans suggests that a trace of this poorly understood strand of hominin lineage survives today, but only in the genes of some Papuans and Pacific islanders.

Named after the cave that yielded the 30,000–50,000-year-old bone, the Denisova nuclear genome follows publication of the same individual’s mitochondrial genome in March¹. From that sequence, Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and his colleagues could tell little, except that the individual, now known to be female, was part of a population long diverged from humans and Neanderthals.

Her approximately 3-billion-letter nuclear genome, reported in this issue of Nature², now provides a more telling glimpse into this mysterious group. It also raises previously unimagined questions about its history and relationship to Neanderthals and humans. “The whole story is incredible. It’s like a surprising Christmas present,” says Carles Lalueza Fox, a palaeogeneticist at Pompeu Fabra University in Barcelona, Spain, who was not involved in the research.

When the ancient genome was compared to a spectrum of modern human populations, a striking relationship emerged. Unlike most groups, Melanesians — inhabitants of Papua New Guinea and islands northeast of Australia — seem to have inherited as much as one-twentieth of their DNA from Denisovan roots. This suggests that after the ancestors of today’s Papuans split from other human populations and migrated east, they interbred with Denisovans, but precisely when, where and to what extent is unclear.

More answers could come from a closer look at Denisovan, human and even Neanderthal DNA. So far, conclusions about interbreeding have been drawn from a relatively small number of human genomes using conservative DNA-analysis methods, says David Reich, a geneticist at Harvard Medical School in Boston, Massachusetts, who led the Denisova analysis. “There may have been many more interactions,” he says. Pääbo says it may be possible to determine roughly when humans interbred with Denisovans by examining the length of DNA segments lurking in various human genomes, with shorter segments corresponding to more shuffling of genes and a longer elapsed time.

A molar discovered in the same cave also yielded mitochondrial DNA resembling that of the finger bone. But the Denisovans were probably more widespread, says Pääbo. Some fossils from China, for example, resemble neither Neanderthals nor modern humans — nor Homo erectus, an earlier human ancestor. Pääbo wonders whether they could be more closely related to Denisovans. His Russian collaborators plan to search for more complete Denisovan fossils that could be matched to others from China.

Chris Stringer, a palaeoanthropologist at London’s Natural History Museum, agrees that Asian fossils, such as the 200,000-year-old Dali skull from central China, could have links to the Denisovans. But he says that firm conclusions about such relationships will have to await the discovery of more complete Denisovan fossils.

Preserved DNA from other Asian fossils would also provide a clearer picture of the Denisovans, which Pääbo, to sidestep controversy, has opted not to call a new species or subspecies of hominin. The challenge will be to make sense of such discoveries and put them in the context of ancient human history, says Lalueza Fox. Palaeoanthropologists are just beginning to scrutinize the Neanderthal genome published earlier this year³ for clues to ancient human history. With the Denisova genome, “they will need to deal with another surprise”, he says.

Is the As-bacterium overhyped? ctd

Carl Zimmer, writing in Slate, considers the evidence:

None of the scientists I spoke to ruled out the possibility that such weird bacteria might exist. Indeed, some of them were co-authors of a 2007 report for the National Academies of Sciences on alien life that called for research into, among other things, arsenic-based biology. But almost to a person, they felt that the NASA team had failed to take some basic precautions to avoid misleading results.

When the NASA scientists took the DNA out of the bacteria, for example, they ought to have taken extra steps to wash away any other kinds of molecules. Without these precautions, arsenic could have simply glommed to the DNA, like gum on a shoe. “It is pretty trivial to do a much better job,” said Rohwer.

In fact, says Harvard microbiologist Alex Bradley, the NASA scientists unknowingly demonstrated the flaws in their own experiment. They immersed the DNA in water as they analyzed it, he points out. Arsenic compounds fall apart quickly in water, so if it really was in the microbe’s genes, it should have broken into fragments, Bradley wrote Sunday in a guest post on the blog We, Beasties. But the DNA remained in large chunks—presumably because it was made of durable phosphate. Bradley got his Ph.D. under MIT professor Roger Summons, a professor at MIT who co-authored the 2007 weird-life report. Summons backs his former student’s critique.

But how could the bacteria be using phosphate when they weren’t getting any in the lab? That was the point of the experiment, after all. It turns out the NASA scientists were feeding the bacteria salts which they freely admit were contaminated with a tiny amount of phosphate. It’s possible, the critics argue, that the bacteria eked out a living on that scarce supply. As Bradley notes, the Sargasso Sea supports plenty of microbes while containing 300 times less phosphate than was present in the lab cultures.

But why rush a critically flawed paper to publication? Zimmer speculates:

“I suspect that NASA may be so desperate for a positive story that they didn’t look for any serious advice from DNA or even microbiology people,” says John Roth of UC-Davis. The experience reminded some of another press conference NASA held in 1996. Scientists unveiled a meteorite from Mars in which they said there were microscopic fossils. A number of critics condemned the report (also published in Science) for making claims it couldn’t back up. And today many scientists think that all of the alleged signs of life in the rocks could have just as easily been made on a lifeless planet.The controversy over the Martian meteorite still sputters on today because they contain only a few alleged fossils, rather than living bacteria. There are only a limited number of tests that scientists can run on the rocks, and their results remain murky. Fortunately, that’s not the case for GFAJ-1. Critics say that a few straightforward tests on the bacteria would show whether they really do have arsenic-based DNA once and for all. And the NASA scientists say they’re ready to hand out GFAJ-1 to researchers who want to study it. This controversy may be burning brightly at the moment, but it probably won’t burn for long.

Is the As-bacterium overhyped?

Obnoxious-even-when-he’s-right atheist and University of Minnesota Morris biologist PZ Myers says “yes.”  The Weiner sequence, it appears, has played out again.

My own speculation that the bacterium might represent the trunk of a new evolutionary tree does now seem, as I expected, reckless.

The piece is long, but non-technical, so bear with us.

Here’s the story. Life on earth uses six elements heavily in its chemistry: carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur, also known as CHNOPS . There are other elements used in small amounts for specialized functions, too: zinc, for instance, is incorporated as a catalyst in certain enzymes. We also use significant quantities of some ions, specifically of sodium, potassium, calcium, and chloride, for osmotic balance and they also play a role in nervous system function and regulation; calcium, obviously, is heavily used in making the matrix of our skeletons. But for the most part, biochemistry is all about CHNOPS.

Here’s part of the periodic table just to remind you of where these atoms are. You should recall from freshman chemistry that the table isn’t just an arbitrary arrangement — it actually is ordered by the properties of the elements, and, for instance, atoms in a column exhibit similar properties. There’s CHNOPS, and notice, just below phosphorous, there’s another atom, arsenic. You’d predict just from looking at the table that arsenic ought to have some chemical similarities to phosphorus, and you’d be right. Arsenic can substitute for phosphorus in many chemical reactions.

This is, in fact, one of the reasons arsenic is toxic. It’s similar, but not identical, to phosphorus, and can take its place in chemical reactions fundamental to life, for instance in the glycolytic pathway of basic metabolism. That it’s not identical, though, means that it actually gums up the process and brings it to a halt, blocking respiration and killing the cell by starving it of ATP.

Got it? Arsenic already participates in earthly chemistry, badly. It’s just off enough from phosphorus to bollix up the biology, so it’s generally bad for us to have it around.

What did the NASA paper do? Scientists started out the project with extremophile bacteria from Mono Lake in California. This is not a pleasant place for most living creatures: it’s an alkali lake with a pH of close to 10, and it also has high concentrations of arsenic (high being about 200 µM) dissolved in it. The bacteria living there were already adapted to tolerate the presence of arsenic, and the mechanism of that would be really interesting to know…but this work didn’t address that.

Next, what they did was culture the bacteria in the lab, and artificially jacked up the arsenic concentration, replacing all the phosphate (PO₄^3-) with arsenate (AsO₄^3-). The cells weren’t happy, growing at a much slower rate on arsenate than phosphate, but they still lived and they still grew. These are tough critters.

They also look different in these conditions. Below, the bacteria in (C) were grown on arsenate with no phosphate, while those in (D) grew on phosphate with no arsenate. The arsenate bacteria are bigger, but thin sections through them reveal that they are actually bloated with large vacuoles. What are they doing building up these fluid-filled spaces inside them? We don’t know, but it may be because some arsenate-containing molecules are less stable in water than their phosphate analogs, so they’re coping by generating internal partitions that exclude water.

What they also found, and this is the cool part, is that they incorporated the arsenate into familiar compounds^*. DNA has a backbone of sugars linked together by phosphate bonds, for instance; in these baceria, some of those phosphates were replaced by arsenate. Some amino acids, serine, tyrosine, and threonine, can be modified by phosphates, and arsenate was substituted there, too. What this tells us is that the machinery of these cells is tolerant enough of the differences between phosphate and arsenate that it can keep on working to some degree no matter which one is present.

So what does it all mean? It means that researchers have found that some earthly bacteria that live in literally poisonous environments are adapted to find the presence of arsenic dramatically less lethal, and that they can even incorporate arsenic into their routine, familiar chemistry.

It doesn’t say a lot about evolutionary history, I’m afraid. These are derived forms of bacteria that are adapting to artificially stringent environmental conditions, and they were found in a geologically young lake — so no, this is not the bacterium primeval. This lake also happens to be on Earth, not Saturn, although maybe being in California gives them extra weirdness points, so I don’t know that it can even say much about extraterrestrial life. It does say that life can survive in a surprisingly broad range of conditions, but we already knew that.

So it’s nice work, a small piece of the story of life, but not quite the earthshaking news the bookmakers were predicting.

More on the As-bacterium discovery

(above) The Mono Lake bacterium.

It’s probably not good that I’m getting this much of my science news through Gawker outlets, but io9′s Alasdair Wilkins provides a sober rundown of NASA’s latest bombshell. One member of the panel that made the announcement, Dr. James Elder, an expert on phospherus, talked about potential industrial application of the bacteria:  

[Elder said] arsenic-based life could be used to help in the cleanup of toxic waste, where the buildup of arsenate is frequently an issue. These organisms would be perfectly suited to break down such waste.

He also said that the discovery of life that doesn’t need phosphorus could have some very intriguing applications in areas where phosphorus is in short supply. Beyond its role in organic chemistry, phosphorus has a bunch of industrial applications. Perhaps its most important role has been as a fertilizer in the Green Revolution, the massive increase in agricultural yields in the last seventy years that’s often credited with saving billions of lives.

The problem is that phosphorus is in increasingly short supply, and that could mean trouble for the continued success of the Green Revolution. Elder says that it will be interesting to examine organisms that have evolved to survive without phosphorus, and this might provide some unexpected solutions to the phosphorus shortage. In particular, he says arsenic-based life could be used to help recover and recycle phosphorus that has already been used in fertilizers.

But the most intriguing idea is to create an entirely new bioenergy technology that’s built around arsenic. Ethanol, an alternative to fossil fuels created from crops, has struggled with efficiency concerns because it takes a lot of phosphorus-based fertilizers to grow the crops in the first place, which often results in a rather troublesome net energy loss. Arsenic-based ethanol, on the other hand, could prove much more efficient, and the fact that it doesn’t have any phosphorus would make it a very unattractive target for outside contaminants.

This is still just science fiction, says Elder, but it’s all within the realm of possibility. It’s entirely conceivable that, thirty years from now, people’s main interaction with arsenic life will be when they go to gas up their cars.

Renowned chemist Dr. Steven Brenner, also on the NASA panel announcing the discovery, argued more research might be necessary to assess the scope of the discovery. The claim of total phospherus-replacement struck him as extraordinary, as arsenic is comparatively inefficient fulfilling the same functions:

 In terms of their role as the structure of DNA, he compared phosphorus to steel and arsenic to aluminum foil – the former makes for strong links in the chains, while the latter is nothing if not a liability. Indeed, enzymes that would attempt to use arsenic to build DNA chains would encounter what he calls “a demon wolf in sheep’s clothing”, a seemingly useful material that continually fails and causes the enzymes to waste a lot of energy in repeatedly making the same links.He also pointed out that we know similar compounds that involve arsenic along with elements like carbon or oxygen tend to be very unstable. Taken together, there are two possibilities here – the enzymes might evolve to get very good at not being fooled by the arsenic, and so only take what little phosphorus there is available to build the DNA chains, or it might conceivably find a way to deal with the weak links. He said there’s a lot of old chemistry that says the latter is impossible, but he also readily admitted:

“Old chemistry can be wrong. As Richard Feynman would say, ‘Science begins when you distrust experts,’ and I’m an expert.”

He said he would want to see a lot more data before he’s convinced, but he did admit this is a fascinating finding regardless and this microbe has a lot to show us, even if the idea of arsenic-based chemistry doesn’t ultimately hold up.

He also raised a rather fascinating possibility, pointing out that his measurements of the weaknesses in the links are based on room temperature. However, if you look at extreme temperature situations, like that of Saturn’s moon Titan where the temperatures hover around -200 degrees Celsius, then a very reactive element like arsenic might actually be useful because it’s more stable there. In fact, he said, it’s possible that arsenic would be more useful than phosphorus on Titan, because you might need the increased reactivity to make biopolymer chains.

Newly discovered bacteria redefines possibilities of biochemistry

What can life be made of? Stanislaw Lem imagined beings made of ice, of uranium, and of precious gems. Now, NASA scientists have discovered organisms made of arsenic. Via Gizmodo’s Jesus Diaz:

NASA scientist Felisa Wolfe Simon will announce that they have found a bacteria whose DNA is completely alien to what we know today. Instead of using phosphorus, the bacteria uses arsenic. All life on Earth is made of six components: carbon, hydrogen, nitrogen, oxygen, phosphorus and sulfur. Every being, from the smallest amoeba to the largest whale, share the same life stream. Our DNA blocks are all the same.But not this one. This one is completely different. Discovered in the poisonous Mono Lake, California, this bacteria is made of arsenic, something that was thought to be completely impossible. While she and other scientists theorized that this could be possible, this is the first discovery. The implications of this discovery are enormous to our understanding of life itself and the possibility of finding beings in other planets that don’t have to be like planet Earth.

No details have been disclosed about the origin or nature of this new life form. We will know more today at 2pm EST but, while this life hasn’t been found in another planet, this discovery does indeed change everything we know about biology.

Now, I have no scientific training–seriously, none at all, I majored in journalism and English–and I’m speculating wildly here from a position of near total ignorance of the biochemistry and eukaryote evolution; but given that that the Mono Lake bacteria has DNA funamentally different from any other observed organism, this could mean that life arose independently more than once on Earth.