Basics: What is a gene?

I mulled over some of the suggestions in my request for basic topics to cover, and I realized that there is no such thing as a simple concept in biology. Some of the ideas required a lot of background in molecular biology, others demand understanding of the philosophy of science, and what I am interested in is teetering way out at the edge of what we know, where definitions often start to break down. Sorry, I have to give up.

Seriously, though, I think that what does exist are simple treatments of complex subjects, so that is what I’m aiming for here: I talk a lot about genes, so let’s just step way back and give a useful definition of a gene. I admit right up front, though, that there are two limitations: I’m going to give a very simplified explanation that fits with a molecular genetics focus (pure geneticists define genes very differently), and I’m going to talk only about eukaryotic/metazoan genes. I tell you right now that if I asked a half dozen different biologists to help me out with this, they’d rip into it and add a thousand qualifiers, and it would never get done. So let’s plunge in and see what a simple version of a gene is.

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February at the Bell

The Bell Museum in Minneapolis is pulling out all the stops in the month of February, celebrating Darwin’s birth month with an orgy of science and sex. I’m going to be there for the events on the 13th and 15th, and I’m really tempted by the talk on the 20th—I’ll have to see if I can get away for that one.

People in Minneapolis/St Paul ought to appreciate that this kind of public outreach is what good museums do, and take advantage of the opportunities!

Bell Museum of Natural History, University of Minnesota
10 Church St. S.E. , Minneapolis, MN 55455, (612) 624-7389

In Feburary, the Bell Museum of Natural History celebrates the birthday of pioneering naturalist Charles
Darwin with a series of discussions and films that explore his life and legacy.

Thurs., Feb. 1, 7 p.m. Bell Museum Auditorium
Film — “Genius”
$7, $5 students, seniors and members
A documentary on Charles Darwin, his historic voyage to the Galapagos Islands, and his most influential work:
The Origin of Species. Highlights include expert analysis and insight into Darwin’s impact on today’s world.

Thurs., Feb. 8, 7 p.m., Bell Museum Auditorium
Film — “Kansas vs. Darwin”
$7, $5 students, seniors and members
In May, 2005 the Kansas state school board held hearings that put Darwin’s theory of evolution on trial. See
for yourself what happened — and why.

Tues., Feb. 13, 6 p.m., Varsity Theater, Dinkytown, Minneapolis
Discussion — Cafe Scientifique: “Understanding Evolution”
$5 Suggested Donation.
A panel of University of Minnesota researchers discusses the science of evolutionary biology, and the history
of America’s cultural response to teaching evolution. Learn about new research from professor and science
blogger PZ Myers, Bell Museum Director Scott Lanyon, and historian of biology Mark Borrello.

Thurs., Feb. 15, 7 p.m., Bell Museum Auditorium
Film (Regional Premier) — “Flock of Dodos”
$7, $5 students, seniors and members
Filmmaker and evolutionary ecologist Randy Olson pokes fun at the battle between evolution and intelligent
design. He travels to his home state of Kansas to consult his mother, Muffy Moose, and confronts her
neighbor, a lawyer backing intelligent design.

Tues., Feb. 20, 6:30 p.m., Bryant-Lake Bowl, 810 W. Lake St., Minneapolis
Discussion — Cafe Scientifique: “Sex, Snails & Evolution”
$5 admission. Doors open at 5:30 p.m.
Cynthia Norton, biologist and Professor of Animal Behavior at the College of St. Catherine discusses
evolutionary biology and sexual selection. Her research into the reproductive behaviors of hermaphroditic snails
is one example of the diversity of sexual behaviors found in nature. What can biologists tell us about the
evolution of sex?

Thurs., Feb. 22, 7 p.m., Bell Museum Auditorium
Film — “Deepest Desires”
$7, $5 students, seniors and members
Does the difference in the way men and women approach sex have an evolutionary basis? See what happens
when a male and female actor are sent to a London university campus with hidden cameras to ask a simple
question: “Will you sleep with me?”

Simplicity

That clever fellow John (Chris) Walken has proposed a useful idea—that we put together simple descriptions of basic concepts in our fields of interest for the edification of any newcomers to science. He picked the magic word Clade to write about first; I don’t know why he didn’t pick “Species”, since he could have just dumped his thesis into one short, simple blog post. Maybe he’ll do that next.

Larry Moran has joined in with a lovely lucid explanation of Evolution. This is very useful, because now whenever a creationist comes along here, we can just tell him or her to go to that post and argue with Larry. If they survive that, then they are worthy of further interaction.

All of my science posts are basic and simple, so I’m not sure what I could write to add to this collection. If anyone has any suggestions, chime in and let me know.

Life of a squid

The heathen at IIDB are talking about squid—it’s infectious, I tell you, and the godless seem especially susceptible—and in particular about this interesting paper on squid fisheries. Squid are on the rise, and are impressively numerous.

We can get an idea of the abundance of squid in the world’s ocean by considering the consumption of cephalopods (mainly squid) from just one cephalopod predator the sperm whale. Sperm whales alone are estimated to consume in excess of 100 million tonnes of cephalopods a year. This is equivalent to the total world fishery catch and probably exceeds half the total biomass of mankind on the earth (Clarke 1983). It is therefore highly likely that the standing biomass of squids within the world’s oceans probably exceeds the total weight of humankind on the earth. Given such importance squid have generally not been given the attention they deserve or have not been incorporated to the degree they need to in ecosystem models. Future research needs to rectify this.

Squid are creatures of speed: they grow fast and die young. Teleosts and cephalopods follow rather different life strategies.

The form of growth of squid is also unique and interesting. Squid just keep growing. They do not show the distinctive flattening in their growth curve shown by their fish competitors. Many species growth can be modeled with exponential or linear curves. The interesting thing is they continue growing even during their maturation phase until they die or are eaten. They seem to achieve this because of a number of unique qualities, (1) they have a protein based metabolism with efficient digestion so food is converted to growth rather than stored, (2) they are efficient feeders, using their suckered arms and beak they can remove only the highly digestible parts of prey and ‘spit out the bones’ and (3) they can grow by continually increasing the number of their muscle fibres (hyperplasia) a feature not shared by their fish counterparts. While juvenile fish recruit new muscle fibres by hyperplasia they reach a point where growth only occurs by increasing the size of existing muscle fibres (hypertrophy). This probably contributes to their flattening growth curve. Alternatively, squid show both hyperplasia and hypertrophy throughout their life span, thus they continue to recruit new fibres as well as increase the size of existing fibres (Figure 1). Such a strategy might account for their continuous growth. All of the above features contribute to the unique form of growth and the ability of squid to grow fast and fill available niches. Their life is very much life-in-the-fast-lane. They are the ‘weeds’ of the sea.

Live fast, die young…and leave a really decrepit corpse, it seems. Here’s a description of a species that really knows how to have a good time.

Much of my Southern Ocean research has focused on the warty squid Moroteuthis ingens. Up until recent years this species was poorly understood and delegated to obscurity due to lack of biological information. However, this species is regularly caught in both fishing and research trawls and my research has focused on New Zealand, The Falkland Islands and more recently Australia’s sub-Antarctic island regions. The biological understanding of this species is now perhaps the best of any sub-Antarctic squid. It is a large squid growing to over 500mm in mantle length and females achieve a much larger size than males. While M. ingens is epipelagic during its juvenile stage it undergoes an ontogentic descent to take up a demersal existence (Jackson 1993). This species has a biologically unusual and interesting reproductive strategy referred to as terminal spawning (Jackson & Mladenov 1994). Although it is a muscular squid, females (and to a lesser extent males) undergo a dramatic change associated with reproduction. Females produce a huge ovary that can reach the size of a rugby ball and weigh as much as a kilogram. In fact the ovary can weigh more than the total body weight of the male. In association with the development of the ovary the female undergoes a dramatic tissue breakdown in its body wall. This process results in a total loss of muscle fibres that transforms the muscular female into something more analogous to a jellyfish and death is associated with spawning. Moroteuthis ingens and other onychoteuthids are important prey for a number of vertebrate predators (at least four mammals, 17 birds, 13 fish, Jackson et al 1998). It is suspected that this tissue breakdown may result in dead individuals floating to the surface where they are accessible to mammals and birds.

Cool stuff…read the whole paper!

Bird brains

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I’m teaching a course in neurobiology this term, and it’s strange how it warps my brain; suddenly I find myself reaching more and more for papers on the nervous system in my reading. It’s not about just keeping up with the subjects I have to present in lectures (although there is that, too), but also with unconsciously gravitating toward the subject in my casual reading, too.

“Unconsciously”…which brings up the question of exactly what consciousness is. One of the papers I put on the pile on my desk was on exactly that subject: Evolution of the neural basis of consciousness: a bird-mammal comparison. I finally got to sit down and read it carefully this afternoon, and although it is an interesting paper and well worth the time, it doesn’t come anywhere near answering the question implied in the title. It is a useful general review of neuroanatomical theories of consciousness—even if it left me feeling they are all full of crap—but in particular it’s an interesting comparative look at avian brain organization.

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Worms and death

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If you’ve seen BladeRunner, you know the short soliloquy at the end by one of the android replicants, Roy, as he’s about to expire from a genetically programmed early death.

“I’ve seen things you people wouldn’t believe. Attack ships on fire off the shoulder of Orion. I watched c-beams…glitter in the dark near Tanhauser Gate. All those…moments will be lost…in time, like tears…in rain. Time…to die.”

There’s an interesting idea here, that death can be an intrinsic property of our existence, a kind of internal mortality clock that is always ticking away, and eventually our time will run out and clunk, we’ll drop dead. There is a germ of truth to it; there are genetic factors that may predispose one to greater longevity, and in the nematode worm C. elegans there are known mutants that can greatly extend the lifetime of the animal under laboratory conditions.

However, in humans only about 25% of the variation in life span can be ascribed to genetic factors to any degree, and even in lab animals where variables can be greatly reduced, only 10-40% of the life span variation has a genetic component. There is a huge amount of chance involved; after all, there aren’t likely to be any genes that give you resistance to being run over by a bus. Life is like a long dice game, and while starting with a good endowment might let you keep playing for a longer time, eventually everyone craps out, and a run of bad luck can wipe out even the richest starting position rapidly.

In between these extremes of genetic predetermination and pure luck, though, a recent paper in Nature Genetics finds another possibility: factors in the organism that are not heritable, yet from an early age can be reasonably good predictors of mortality.

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Evolving motors

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As we are so often reminded by proponents of Intelligent Design creationism, we contain molecular “machines” and “motors”. They don’t really explain how these motors came to be other than to foist the problem off on some invisible unspecified Designer, which is a poor way to do science—it’s more of a way to make excuses to not do science.

Evolution, on the other hand, provides a useful framework for trying to address the problem of the origin of molecular motors. We have a theory—common descent—that makes specific predictions—that there will be a nested hierarchy of differences between motors in different species. Phylogenetic analysis of variations between species allows us to reconstruct the history of a molecule with far more specificity than “Sometime between 6,000 and 4 billion years ago, a god or aliens (or aliens created by a god) conjured this molecule into existence by unknown and unknowable means”.

Richards and Cavalier-Smith (2005) have applied tested biological techniques to a specific motor molecule, myosin, and have used that information to assemble a picture of the phylogenetic history of eukaryotes.

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Flitting through Saturday at SICB

Rather than burning out, I decided I just needed a happy fun day at the SICB meetings, so I put away the notepad and flitted about from session to session to check out a semi-random subset of the diverse talks available here. So I listened to talks on jaw articulations and feeding mechanisms in cartilaginous fishes; the direct developing frog, Eleutherodactylus coqui; Hox gene expression in the fins of Polyodon (which was really cool—that curious HoxD gene flip across the digits may be a primitive condition, rather than a derived tetrapod state); biomechanical properties of spider webs; the physics of snake slithering; and the role of university based natural history museums. It was very relaxing.

One thing I wish more people in the lay public could understand is that science is just plain fun, and that scientists do things because the natural world is so beautiful and so engrossing. Maybe these scientific meetings should be accompanied by a few lectures open to the public…

How I spent another morning at SICB

Everyone can stop now, my brain is full. Seriously, this is a painful meeting: my usual strategy at science meetings is to be picky and see just a few talks in a few sessions, to avoid burnout…but at this one, I go to one session and sit through the whole thing, and at the breaks I look at the program and moan over the concurrent sessions I have to be missing. I have to come to SICB more often, that’s for sure.

I do have one major complaint, though: PowerPoint abuse. The evolution of slides has continued apace since my graduate school days, when one slide was one photograph, developed in a darkroom ourselves, and then carefully labeled with letraset lettering, photographed again on a copy stand with slide film, and then sent off for processing (usually the day before the meeting, so there was no slack for redoing anything.) Now the slides are all huge multipaneled affairs with data packed into tiny little boxes that fade in as the speaker does a tarantella on the keyboard, and it’s getting a little irritating. Most of the talks this morning would, at some point, throw up a gigantic, intricately detailed cladogram with 50 taxa and branch points all labeled and circles and arrows and scary tiny lettering all around. Any one slide legitimately represents something that the speaker could talk about for an hour, no problem, but wham-bam-zoom, they’ll run through 20 of them in 20 minutes. If the information density is going to be this high, they ought to set it up so they can beam these monster slides to our laptops over the wireless network, so we can actually try to absorb it into our heads in some way other than being battered about the cranium with it.

I spent Friday morning at the Key Transitions in Animal Evolution symposium.

  • F. Boero: Cnidarian milestones in metazoan evolution. This talk was a bit thin on the data, but it was presented more as a conceptual overview, so I let it go. The idea was simple: it was an anti-Great Chain of Being talk, pointing out that sponges and especially cnidarians were darned important creatures that ought to be appreciated for the fact that they bear the seeds of everything we consider especially essential to the bilateria. They have bilateral symmetry, many have supporting skeletons, polyp buds have an internal mass that corresponds in many ways to mesoderm, they have body cavities, the modularity of their development has affinities to bilaterian metamery, and most interestingly, cnidarian planula larvae have specialized concentrations of nerve cells that resemble a brain. One weird twist (I love weird twists) was the idea that the cnidocyst was such an incredibly potent adaptation that the cnidaria didn’t need all the elaborate complexity of the bilateria to succeed, and that maybe an important milestone that was a precursor to our evolution was the loss of cnidocysts.

  • B. F. Lang: The evolutionary transition from protists to Metazoa: mitochondrial genome organization and phylogenomic analyses based on nuclear and mitochondrial genes. I was rather far over my head in this talk; it was hardcore phylogenetic analysis of really distant branch points in our evolutionary history—this fellow is trying to puzzle out the branch point between fungi and animals. I mainly just jotted down a few names I’ll have to look up later: the Ichthyosporia, which are fungal-like cells with amoeboid stages, the Nuclearia, which are low on the branch leading to the fungi, the Capsaspora, which similarly lie on a branch leading to the animals, and the Apusozoa, bikont flagellates that have been poorly characterized so far.

  • D.K. Jacobs: Origins of sensory and neural organization in basal metazoa. The cnidarian fan club was out in force in this session. This was a talk on the identification of cnidarian genes usually associated with nervous system and sensory organ development and function, the point being that all of the precursors to our rather more elaborate neural processing system are there in jellyfish. There were a few places where I wondered if he was going a little too far—there’s no reason to assume that finding a gene that is used in the vertebrate brain in a cnidarian means that gene has a similar function there—but still an interesting talk. One cute idea was that the choanocytes of sponges can also be thought of as sensory organs, and also that neural genes seem to share functions with nephridia/kidneys, too, raising the possibility of a primitive link between excretion and the origins of the nervous system. (Watch Fox News, and this possibility will seem even more likely).

  • G. Wagner: Do genome duplications play a role in key transitions? This is the second time I’ve heard this Wagner fellow talk, and he keeps making me think. He brought up a familiar correlation: in vertebrate evolution, we see signs that there are major gene duplications at the same time that we see major radiations. In the vertebrate lineage, for instance, we see two whole genome duplications, and the conceit is that these increases in genetic material provided the substrate for more sophisticated developmental events that were the source of our success; similarly, the even more successful teleosts show signs of a third round of duplications. Wagner objected, pointing out that there are many highly successful groups that did not exhibit these duplications (arthropods, insect, mammals, and birds, for instance), and that others, such as plants and sturgeon, have duplications but no subsequent radiation. He argued that it was an artifact, not evidence of a causal relationship. The rapid expansion of a lineage during an adaptive radiation would act to preserve and propagate any genetic quirks of the founding population. The duplications are neither necessary nor sufficient to instigate a key transition. One point that came up very briefly in the Q&A was that we developmental biologists are a bit obsessive about regulatory genes like the Hox genes and think those are indicative of importance, but that there are also duplications in, for instance, the glyocolytic enzymes that also correspond to the major transitions.

  • N.W. Blackstone: Foods-eye view of the transition from basal metazoans to bilaterians. This was another weird talk that came from a completely different perspective and made me think. It might actually be a little too weird, but it’s still provocative and interesting. Blackstone is looking at everything from the perspective of metabolic signaling—he’s clearly one of those crazy people coming out of the bacterial tradition. Cells communicate with one another with the byproducts of metabolism, where the redox state of membrane proteins are read as indicators of the internal state of the cells (he later calls this “honest signaling”, because there aren’t any intermediates between the cell and the expression of its metabolic state). The big innovation in the eukaryotes was to escape volume constraints by folding their chemiosmotic membranes into the interior of the organism, and the major animal innovation was the evolution of the mouth, which allowed specialized acquisition and processing of food patches. Subsequent evolution was to allow the animal to sense and seek out and exploit food patches in an environment where they were dispersed in a non-uniform manner. Another interesting tangent was the question of cancer: long-lived sponges and cnidarians don’t get cancer. His explanation was that it was because their cells use that “honest” metabolic signaling, so that rogue cells don’t have a way to trick the organism into allowing them to use more resources than they actually need; the only way to signal is to exhibit genuine metabolic distress, and cells with metabolic problems will die. Our cells have these indirect, multi-layered signaling mechanisms that allow cancer cells to “lie” to the organism as a whole.

  • P. Cartwright: Rocks and clocks: integrating fossils and molecules to date transitions in early animal evolution. Molecular phylogeny is a useful tool to find patterns, and recognize branch points; this information needs to be integrated with fossil date to calibrate the clock and anchor those events to specific dates. This work was a combined effort to put together a catalog of 18s and 28s trees, and use fossil evidence to constrain the timing of the events in a metazoan cladogram. I wasn’t entirely convinced that they’d overcome the obvious problems—fossils can provide a minimum but not a maximum age—but as an excuse to show lots of pictures of Cambrian and pre-Cambrian fossils, I wasn’t going to complain. In particular, they had some amazing cnidarian fossils from 500 million year old rocks in Utah that were pretty much indistinguishable from modern taxa; jellyfish definitely are in a good niche. In her final table of conclusions (which flew by much too quickly!), she pinned the origin of the metazoa to 950mya, the deuterostomes to 539mya, the lophotrochozoa to 537mya, the ecdysozoa to 541mya, and the placozoa to 61mya (!). The clustering of those significant groups to right around the Cambrian was an indication that the Cambrian explosion was real.

  • M. Q. Martindale: The developmental basis of body plan organization in the Eumetazoa. Uh, Mark can talk really, really fast. My notes are a rather unreadable scrawl as I tried to keep up. A general point: he emphasized that much of what we can expect to see from developmental biologists is going to look like the intricate ‘circuit diagrams’ that Eric Davidson has published, where the fundamental unit is a network of gene interactions that define a cell state. He showed Davidson’s endomesoderm specification kernel for echinoderms, for instance, and then went through each of the genes involved and showed that they are all also present in Nematostella, and that they are almost all involved in endomesoderm specification there, as well. While the network has not been identified in the cnidarian, only the components, I do’t think we’ll be too surprised to see similar interactions appear as the details are worked out.

  • D.J. Miller: Implications of cnidarian gene expression data for the origins of bilaterality: is the glass half full or half empty. Where Martindale was all about the similarities, Miller was all about the differences. He’s working with a cnidarian, too, but a different one, Acropora. He was also explaining the expression of important early patterning genes, but one very interesting difference is that he looked at Emx and Otx, homologs to anterior-posterior genes in the bilateria that are expressed in the anterior end of those animals—but are expressed at opposite ends of the Acropora planula from each other. While some gene functions are conserved, there is no simple correspondence along the body axis.

  • J. Extavour: Urbilaterian reproduction. A different sort of talk: this one was about the nature of Urbilaterian germ cells. She made the case that one of the key steps necessary to the evolution of true multicellularity was the sequestration of a distinct stem cell population that was specialized to minimize mutation with a greatly reduced mitotic rate, reduced transcription, and with mechanisms to reduce the activity of transposable elements. This was part of the process of making the fitness of individual cells take a backseat to the overall fitness of the organism.

  • P.W.H. Holland: More than one way to make a worm. This talk was fun. He started with the idea of the worm, a flexible, elongated, motile tube, and showed that “worm” was a successful form that one could find scattered across the phyla of the bilateria, and that the urbilaterian was almost certainly a worm. He then raised two questions: are there examples of more derived forms that have secondarily given up features to revert to “wormness” (he gave one example, arguing that the hagfish was basically a chordate worm); and more interestingly, are there any examples of organisms that have independently evolved into a worm? He then showed us a movie of a creature that definitely looked like a worm; on first sight, it looked like a nematode, but rather than undulating and crawling it did a strange corkscrew curl. It’s called Buddenbrockia, and it’s a parasite found inside bryozoans. closer examination showed that it is a sealed hollow tube, completely mouthless and without a gut, and with no sensory organs, and that its interior is lined with 4 blocks of longitudinal muscle. It looked like something from outer space, if you asked me. Inside that tube, though, can be found flagellated spores that look like myxozoans. Molecular phylogeny reveals that it is a myxozoan, and that it is nested within the cnidaria. The idea is that this wormlike animal was built by breaking down a cnidarian and building it up again, and so represents a worm that has evolved independently of the Eubilateria—a worm is apparently a kind of universally basic form to take. Very cool!