There was a time when the publication of the entire sequence of a genome--any genome--was exciting news. I don't have any particular passion about Haemophilus influenzae, a microbe that can cause the flu various infections. But in 1997 it was the first species to have its genome sequenced. It became immensely fascinating, simply because we could now, for the first time, scan all of its genes. Now the global genome factory is cranking away so quickly--with over five hundred sequences published and over two thousand in the pipeline--that a new genome is not necessarily news. There has to be something striking, biologically speaking, for it to light up the radar. My personal radar lit up last month, with a monkey genome, because of the clues it offered to our own deep primate history, and to the question of how new genes evolve. And today, the radar lights up again, with the genome of an opossum.
As a kid I always found it strange that along with the raccoons and the squirrels and the deer and the foxes and all the other placental mammals I saw here in the Northeastern U.S., there was a single species of mammal with a pouch. The opossum wandered through our lives, waddling across a road or scurrying along a branch, giving us a blank, primordial glare. It was the lone representative in my own experience of one of the three great lineages of mammal evolution, the marsupials.
The oldest lineage of mammals are the monotremes, which include platypuses. They still lays eggs like reptiles and birds. The ancestors of marsupial and placental mammals split off from monotremes, after which they evolved the ability to develop inside their mothers without an egg. The ancestors of marsupials and placental mammals then diverged. Paleontologists have found fossils of marsupial-related mammals dating back 135 million years; the split between the forerunners of today's marsupials and placentals must have occurred earlier still, perhaps as long ago as 180 million years. There are many features that separate marsupials and placental mammals, but the most obvious one has to do with how they are born. Placental babies spend a long time developing in the womb before being pushed out by their mother. Marsupial babies squirm out of their mothers much earlier and continue developing in a pouch, where they can nurse.
Today, scientists published the first complete genome of a marsupial. It's not the skanky prowler of my youth (Didelphis virginiana), but a smaller, cuter relative from South America known as the short-tailed opossum, Monodelphis domestica. Scientists have learned a lot from studying the short-tailed opossum, gaining clues to human disorders such as skin cancer and high cholesterol. Their experience lifted M. domestica to the top of the list of species for genome sequencing.
But the opossum is also interesting for what it tells us about our evolutionary history. If we examine the genome of a monkey or a horse or a dog, we're still looking relatively close relatives. Like us, each of them is yet another variation on the placental mammal. We all share an ancestor that already had a placenta and a lot of other biological features. Until today, we had to travel very far beyond placental mammals to find another relative whose genome has been sequenced: the chicken. The common ancestor of chickens and us was a cold-blooded reptile-like creature that lived 300 million years ago. So the opossum falls nicely right in the middle of that gap.
Once the opossum team sequenced the raw code of the genome they began to dissect it. They counted up 18,648 genes (remarkably close to our own total at the moment). They matched opossum genes to related versions in placental mammals, and also looked at the parts of the genome that don't encode proteins. They looked at the chromosomes of opossums as well. Over time, giant chunks of mammal chromosomes also get flipped in reverse, and by comparing the opossum genome to other mammal genomes, scientists can reconstruct the overall look of the chromosomes of our common ancestor some 180 million years ago.
Some of the conclusions the opossum scientists draw have a familiar ring. They're similar to the ones I wrote about in my post on the monkey genome. They found further evidence that many new genes are produced through the duplication of old ones. As with other species, the genome of opossum has been overrun with genomic parasites, virus-like stretches of DNA that can make new copies of themselves. These genomic parasites have mutated over time, and in some cases they've been tamed by our own genes to serve useful functions.
But the opossum genome also has some new lessons of its own, which I'll explain below...
1. The Shadow Network. Some parts of genomes are very different from species to species, and some parts are nearly identical. The differences arise through mutations, which change the sequence of DNA in an animal. In some cases, a mutation spreads throughout an entire species because it creates a beneficial change that's favored by natural selection. In other cases, though, the mutation doesn't cause any noticeable difference to an animal's well-being, but it spreads anyway thanks to random reproductive luck. Harmful mutations, on the other hand, generally remain rare, because they don't boost reproductive success. When scientists discover a stretch of DNA that's very similar from one species to the next, that similarity is a sign that the stretch plays a very important function that cannot be easily altered.
In recent years scientists have been surveying the 98% of the human genome that does not carry genes that encode proteins, comparing it to the non-coding regions of other genomes. There are lots of differences from species to species, which isn't too surprising. After all, the dead remnant of a virus lodged in our genome can acquire a mutation without having much effect on our well-being. What is surprising is that here and there in this genomic wasteland there are stretches of DNA that are nearly identical from species to species. Scientists suspect that these segments have some important function that lets them resist the eroding winds of mutation.
Pinpointing these conserved regions is tricky business, because they can be so deeply hidden in unconserved expanses of DNA. The more species a scientists can compare, the easier it becomes to pick them out. The opossum offers a crucial point of comparison, situated as it is between us and chickens on the evolutionary tree. The opossum genome team found a vast number of non-coding elements--well over 100,000--that can be found in humans, opossums, and chickens. They've stuck around for over 300 million years.
This does not mean that all conserved non-coding elements were plugged into life by some unseen hand billions of years ago. By scanning the opossum genome, scientists discovered that it lacks a number of non-coding elements that are conserved in placental mammals. That means that these elements must have evolved into their essential form after our ancestors split off from the ancestors of opossums. In fact, the scientists estimate that 95% of the innovations in the genomes of placental mammals are of this sort. So how did these new elements come into being? Again, the opossum genome offers clues. It appears that in many cases, conserved non-coding elements evolved from genomic parasites. These useless stretches of DNA mutated in such a way that they began to play a useful function.
Figuring out exactly what these regions do in our bodies will keep many scientists busy for decades. It's that smelly, dirty business of actually doing experiments, rather than just sweeping through the abstract realm of genome space. But some early experiments indicate that conserved non-coding elements may act like a shadow network of switches, turning protein-coding genes on and off. Making sure the right proteins get made at the right time is very important, particularly for developing bodies from eggs. In fact, one of the fastest-evolving parts of human DNA appears in a non-coding element that influences the development of the brain.
2. Shutting Down the X. Biologists do not study evolution by making up stories about the distant past. They build hypotheses, which they then test against new evidence.
Consider, for example, the X chromosome. If you're a man, you've got one, which you inherited from your mother. If you're a woman, you got a copy from both mom and dad. That means that women carry twice as many X chromosome genes as men. But women do not churn out twice as many X-chromosome proteins as men. Instead, the cells of woman--and of all female placental mammals--keep most of the genes on one of the X chromosomes shut down.
This shut-down takes place through a baroque process. Dad's X was shut down in his sperm. After his sperm fertilized one of mom's eggs, his X switched back on. Only later, as the embryo developed, did most of the genes on one of the X chromosomes shut down. It's a matter of random chance from cell to cell whether it's the father's or mother's that shuts down. (A digression: this is how female cats get tortoise shell coats: each X chromosome may carry a different fur-color gene.)
Opossums--and all other marsuplials studied so far--also shut down X genes, but through a different, simpler means. As a rule, the father's X chromosome gets switched off in female embryos. This difference led some scientists to propose that opossums carry the original X-silencing mechanism, and the roundabout off-on-off mechanism evolved later in placental mammals. The opossum genome provides a chance to test this hypothesis. The possum posse looked for the gene that manages the silencing of the placental X chromosome. It's called XIST, and it turns out that in the opossum, XIST does not exist. They also looked for repeating sequences of DNA on the X chromosomes of placental mammals that XIST somehow uses to spread its silencing. The opossum doesn't have these repeating sequences either. So it does indeed appear that our peculiar way of silencing the X is a relatively new feature of mammal evolution. This hypothesis also explains why the scientists found that the human X chromosome has been subject to far less chopping and flipping than the opossum's. These mutations appear to have disrupted the system for silencing genes on the X chromosome in placental mammals. In marsupials, they aren't so dangerous.
3. Not So Primitive After All. It's tempting to look at those weird opossums as living fossils, embodying our own distant ancestry. It's true that in some ways, like the way they silence the X chromosome, they represent the primitive condition of early mammals. But we can't assume that they're primitive in all ways. Many scientists, for example, have claimed that marsupials have a primitive immune system. They based their claim on their inability to find a lot of the signaling molecules that placental mammals like ourselves use to create a complex surveillance network against pathogens.
It turns out, however, that marsupials do indeed have quite a sophisticated network of their own. The opossum genome team was able to identify a lot of genes for immune signals, as well as for receptors and other important molecules in the immune system. Previous scientists had suffered from a kind of inadvertent chauvinism. They could not find our own immune system in marsupials, and so they assumed that marsupials didn't have much of an immune system at all. They do, it turns out--but just not ours. In hindsight, that makes sense. Marsupial babies are exquisitely vulnerable to infection when they creep out of the womb and begin to nurse in their mother's pouch. It appears that they are protected by their own immune system, and a potent immunological cocktail mixed into their mother's milk. And while this immune system is different from our own, it's sophisticated as well.
What's striking about genome papers is how often they don't address what seems to be most obvious about the species from which the genome came from. What's the most obvious difference between opossums and us? That pouch. Yet the new opossum papers (in Nature and in Genome Research) don't say boo on the evolution of pouches and placentas. Marsupials actually have placentas, but theirs are not as extensive as those of placental mammals. So one has to wonder, did our own ancestors have pouches? Is the opossum in this respect a primitive vestige of our own past, an intermediate on the path from egg-laying? Or does it carry an innovation as new as the placentas that we all depended on in the womb? A few hints come from Eomaia, a 125-million year old mammal whose fossils have been found in China. It branched off early on the lineage leading to living placental mammals, but it still had odd bones projecting from its hips called epipubic bones. There's been some suggestion that epipubic bones are a sure sign of a pouch. But the link isn't clear yet. Perhaps there are genetic fossils lurking in our genomes and the genomes of opossums that will someday tell us if our great-great-great (etc.) grandmothers raised their young in pouches.
Source: Mikkelsen, et al, "Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences," Nature, doi:10.1038/nature05805 (Genome Research is also publishing some related papers.)
Photo credit: Paul Samollow, Southwest Foundation for Biomedical Research, San Antonio.
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Egg-laying echidnas have pouches too, so I'm betting on the last common ancestor of mammals having a pouch...
"XIST does not exist" may now be my third-favorite biological sentence. After "Ruminants ruminate" and "Alimentary, my dear hoatzin."
I will never forget the meaning of Didelphia, because when one of my mates in the zoology class asked about the male genitalia in these animals the (female) lecturer replied unfortunately, only one.
A quick microbiology pedanticism. H. influenzae cannot ever cause the flu. The name derives from this organism being cultured from the lungs of flu patients in the late 19th early 20th century (see Barry's The Great Influenza). It is associated with neonatal meningitis (HiB vaccine prevents this) and respiratory infections on top of influenza and in the immune compromised. Flu, by definition, is infection with the influenza virus.
Thanks Paul. Will fix.
Just came across this from the BBC News site: '"This marsupial is a bit different in that the young are not kept in a pouch; they just dangle off the teats," observed Jenny Graves from the Australian National University.'
Maybe that explains the silence on the pouch.. Although saying that the young are not in it doesn't necessarily mean that they don't have it of course.
Thanks, Jan-Maarten [#6] The short-tailed opossum is indeed a bit odd in this respect. Most opossum have pouches (see here), as do most other marsupials. So in some lineages, the pouch is lost. But the offspring still come out of the mother very early (a couple weeks is all it takes!) and then continue to developed attached to mom. Very unplacental.
I'm at CSHL where the Biology of Genomes meeting is going on. One of the themes that's emerging seems to be that while conserved noncoding regions are often important for regulation, regulatory regions are evolving at rates that are not quite as fast as bulk noncoding DNA...but much faster than coding regions. In other words, there is probably lots more convergent evolution in the regulatory systems than in the proteins.
I'm trying to do a few posts on the meeting, but it's packed and I'm only watching it on the streaming video.
>>and then continue to developed attached to mom. Very unplacental.
Carl, you don't have kids, do you? I'm here to tell ya, the little buggers don't really support themselves for many, many years. I'm just saying...
When I heard about this on NPR this morning I just knew you'd have it digested for me like this. Thanks so much, Carl. Half the time I come in here, I feel I should be paying tuition.
From what I know the lack of a pouch in a marsupial is considered a primitive condition. The first marsupials produced folds in the skin to hold their young much as their monotreme ancestors did.
Note that primitive placental mammals (the Golden Mole from Africa for instance) also have a cloaca as marsupials and monotremes do.
Primitive? Heck, these may have been the last ones intelligently designed, I think it's been downhill since
Chironectes minimus ...
Both sexes have a well-developed pouch. In females a sphincter muscle closes the pouch to create an airtight (and watertight) compartment for the young, who are able to endure several minutes without oxygen. In males the sphincter is not as watertight as that of females. However, it serves to hold the scrotum which is drawn up into it when the animal swims or runs fast.
Is there anything known about the developmental biology of pouches at the molecular/genetic level? Perhaps it is 'Better to remain silent and be thought a fool than to speak out and remove all doubt". Pouchness more likely a function of some small changes in regulatory signals than whole genes being present or absent, and in any case without multiple marsupial genomes to compare to you aren't going to be able to confidently find a marsupial-specific signal (i.e. the difference you see might be idiosyncratic to oppossums). There is a wallaby sequence in progress (in Australia, of course!) which would be a step in that direction.
But to really get some traction, somebody would need to set up a lab full of 'possums and do mutagenesis to look for some pouchless mutants.
Error?
"They still lays eggs like reptiles and birds"
If you'll allow a small critique of an otherwise insightful post, this statement is incorrect. Both the opossum and humans are extant species who shared a common ancestor more recently than either did with the chicken. Opossums and humans are equally distant from that shared ancestor.
In technical terms, you cannot read across terminal nodes on a phylogeny, because every internal node can be rotated without affecting the accuracy of the topology. The tree you're imagining might have chickens on the left and humans on the right with opossum in the middle, but you can rotate the node representing the common ancestor of humans and opossums and put humans in the middle and this would be exactly as accurate.
Assigning relevance to the order of terminal nodes is probably the biggest misconception about phylogenies, and unfortunately it shows up pretty often in both popular press and scientific discussions. I saw a conference presentation not even one week ago that talked of "trends across the phylogeny" (i.e., across the living species depicted), which is meaningless (as opposed to historical trends that extend back in time along the branches of the tree).
http://evolution.berkeley.edu/evosite/evo101/IIB2Notladders.shtml
Yeah--now that I look at it, that phrase doesn't work well. Where's a really good metaphor when you need it...?
These critters are house pets???
Great post.. Really gets you thinking.
"As a kid I always found it strange that along with the raccoons and the squirrels and the deer and the foxes and all the other placental mammals I saw here in the Northeastern U.S., there was a single species of mammal with a pouch."
I always had the same thoughts...
Carl, thanks to you keeping up with this particular branch of science is easier. And thanks to TR Gregory for clarifying the rotation of nodes in phylogenetic trees. I have always had some unexpressed doubt about this.
Manual TrackBack
There is another interesting point - marsupial and placental convergence not mentioned in article. There is not only striking similarity between marsupial and placental moles but especially between skulls of thylacinus (marsupial wolf) and red fox (Vulpes vulpes and not as thought to canis lupus). Skulls are so similar that according Dawkins even Oxfors students have problem to distinguish between them in their exams (in this case tell them apart from dog skulls).
Another interesting point is stripes on marsupial wolf back. Almost exactly such stripes have only on their back Afrikan Zebra duiker. Obviously to explain function of such stripes is very difficult and we should reconsider professor Adolf Portmann no-darwinian interpretation of colors and patterns on animals as "Selbstdarstellung".
Such similarities and convergence are hardly to be explainable by random mutation and natural selection. Such convergence testify more of internal forces of unknown nature. It might be orthogenesis, nomogenesis or by professor John Davison Prescribed evolutionary hypothesis.
Btw. even many striking abilities of parasites and especially their hosts described in Parasite Rex (Mr. Zimmer book was translated btw last year into Czech) support on my opinion other forces behind evolution as darwinian random mutation and natural selection.
Thank you Martin for your unflagging support.
"The applause of a single human being is of great consequence."
Samuel Johnson
"A past evolution is undeniable, a present evolution undemonstrable."
John A. Davison
The entire Darwinian fairy tale is without foundation. The only demonstrable role for selection, natural or artificial, WAS AND STILL IS to elaborate intraspecific varieties, or in some instances subspecies, none of which WERE or ARE incipient species anyway. Creative evolution, a phenomenon of the distant past, proceeded driven entirely from within with the only role for the environment being to provide a stimulus and the necessary milieu permitting those scheduled events to take place. Just as ontogeny proceeds controlled entirely by information preformed in the egg, so has phylogeny proceeded the same way. We do not see evolution in action but rather the terminal irreversible, immutable orthogenetic products of a long since finished phenomenon just as Linnaeus, Cuvier, Owen and Agassiz all instinctively assumed. Homo sapiens is apparently the terminal mammalian product and probably the last mammal species ever to appear.
The Darwinian fairy tale is without question the longest lasting continuous demonstration of mass hysteria ever produced by a remarkably fertile human imagination. It is the most perfectly failed hypothesis in the history of science, dwarfing both the Phlogiston of Chemistry and the Ether of Physics. Ether, Selection, Phlogiston, ESP, extrasensory perception indeed!
The elimination of both the Lamarckian and Darwinian fantasies has led me, with the aid of my several brilliant sources, to postulate the only conceivable explanation summarized in the Prescribed Evolutionary Hypothesis (PEH). The only real issue has always been the MECHANISM for phylogeny. The PEH along with the Semi-Meiotic Hypothesis (SMH) provide that mechanism which is now for all time next to the works of the great biologists whose common and largely independent findings permit of no other satisfactory explanation for the great mystery of organic evolution.
As for both ontogeny and phylogeny, intimate components of the same reproductive continuum -
"Neither in the one nor in the other is there room for chance."
Leo Berg, Nomogenesis, page 134
"A past evolution is undeniable, a present evolution undemonstrable."
John A. Davison
A reminder: please post comments here about this blog entry, not manifestos that include self-quotation.
*my emphasis
What would these "other forces" be? Are they capable of being observed and measured or would they be "spirit forces" thus being invisible to science?
The Darwinian fairy tale is without question the longest lasting continuous demonstration of mass hysteria ever produced by a remarkably fertile human imagination.
Wait. It's lasted only what, one hundred and fifty years?
Most mass religions have lasted ten times as long. Now, that's definitely 'longest'.
Sorry Carl, don't want to derail the thread, delete this post if you deem it inappropriate. This isn't Pharyngula, after all. :-)
Alan Fox and other forces.
The most interesting part of Carl Zimmer book are besides complicated life cycles and "behaviour" of parasatises the fact that some kind of worms being infected start to eat some special kind of (poisonous) leaves that help them get rid of parasites. It's beyond my imagination - having darwinistic hat for a moment - how random mutation can lead to wiring such instinct into DNA. One should accept either fact that random beneficial experience can be somehow wired into DNA or that such behaviour was prescribed from the beginning.
Everything in the universe is material or it wouldn't be there. That includes the directions for the development of each creature still extant. The directions that produced each new species from its reproductive predecessor may no longer be available for direct analysis but that such instructions once existed cannot be denied by any objective investigator. I summarized the situation at Richard Dawkins' fan club with my one and only thread which produced over 60,000 views in little more than a week at which time I was summarily banned and denied any further viewing of that blog from this computer.
"God or Gods are dead but must have once existed."
Thus, it is unecessary to assume a living God or Gods which may or may not still exist. Gods are like that. All that is required is their past existence which cannot be denied except by those poor souls whose congenital, "prescribed, "dyed-in-the-wool," "born that way," mentalities will not permit the recognition that there was what Robert Broom claimed was a Plan, a word he had the temerity to capitalize.
"Those who consider that all the strange course of evolution is an accident, or a series of accidents, are quite at liberty to do so. I believe there is a Plan, and though in the slow course of evolution there have been ups and downs and what look like mistakes, the plan has gone on; and we may feel sure that it cannot fail to reach its goal."
Finding the Missing Link, page 101.
My cardinal sin has been to extend Broom's analysis and conclude that the Plan has already been realized and terminated with the production of Homo sapiens a mere 100,000 years or so ago. One of several of my unanswered challenges is to produce convincing evidence for a younger mammalian species than ourselves.
"Another life long determinist put his finger on the problem with which we unfortunately still are grappling -
"Then there are the fanatical atheists whise intolerance is the same as that of the religious fanatics, and it springs from the same source... They are creatures who can't hear the music of the spheres."
and
"Our actions should be based on the ever-present awareness that human beings in their thinking, feeling, and acting ARE NOT FREE but are just as causally bound as the stars in their motion."
Albert Einstein, my emphasis.
Everything that has been revealed by both the undeniable fossil record and the experimental laboratory pleads in favor of a scheduled scenario and absolutely nothing precludes it.
"A past evolution is undeniable, a present evolution undemonstrable."
John A. Davison
Bong!!! After the infraction of the commenting rules that you just witnessed above, the banning machine has just switched on. For those who regret that they will no longer be able to read Davison's manifestos, feel free to visit his own blog here. A note for the perplexed--there is only post on his blog, which he updates with comments.
Mr. Zimmer,
are there please any new information / link available about healing Crohn disease and colitide via application of parasites?
For those who regret that they will no longer be able to read Davison's manifestos, feel free to visit his own blog here.
I do not recommed anyone to try the link. Probably some Pharyngulist send to John blog a message that contain the collected writings from Charles Darwin, Karl Marx and Iljic Lenin. No help - you will choke your browser.
False dichotomy. That complex innate behaviour is programmed into organisms such as honeybees, termites, beavers, etc., is self-evident. How such programming works via DNA coding is far from being well understood. This says nothing about how such mechanisms arose.Your spirit frontloader has the identical problem to create the mechanism from thin air.
BTW, Martin, John was never banned at my blog, so it is still available to both of you should you wear out your welcomes elsewhere.
Man, seeing long, spammy rants like that really makes me want to order a pizza, for some reason. . . .
There is another interesting point - marsupial and placental convergence not mentioned in article. There is not only striking similarity between marsupial and placental moles but especially between skulls of thylacinus (marsupial wolf) and red fox (Vulpes vulpes and not as thought to canis lupus). Skulls are so similar that according Dawkins even Oxfors students have problem to distinguish between them in their exams (in this case tell them apart from dog skulls).
I don't know about Oxfors, but I bet at Oxford Zoology the good students have no problem telling a placental wolf from a marsupial wolf. It's quite simple really.
...but I bet at Oxford Zoology the good students have no problem telling a placental wolf from a marsupial wolf.
You bet on wrong card. According Dawkins:
"Zoology students at Oxford had to identify 100 zoological specimens as part of the final exam. Word soon got around that, if ever a 'dog' skull was given, it was safe to identify it as Thylacinus on the grounds that anything as obvious as a dog skull had to be a catch. Then one year the examiners, to their credit, double bluffed and put in a real dog skull. The easiest way to tell the difference is by the two prominent holes in the palate bone, which are characteristic of marsupials generally."
So if you see skulls from side you have to know dental formula to tell them apart. If you forget the formula you will not tell them apart. But maybe you are better than Oxford students in identification animal skulls...
"I don't know about Oxfors, but I bet at Oxford Zoology the good students have no problem telling a placental wolf from a marsupial wolf. It's quite simple really."
Real simple, the placental wolf is most likely to be the one breathing.