Razib Khan has been dropping hints that some big story about human evolution was about to break. Finally the official announcements are here and it is quite a story. "Archaic" humans separate from Neanderthals bred with some human populations and some humans alive today carry some of their genes. Is that cool or what?
Researchers have discovered evidence of a distinct group of "archaic" humans existing outside of Africa more than 30,000 years ago at a time when Neanderthals are thought to have dominated Europe and Asia. But genetic testing shows that members of this new group were not Neanderthals, and they interbred with the ancestors of some modern humans who are alive today.
Well, if two such groups are possible is there a third group waiting to be identified? In theory we should be able to detect the presence of other lost groups that inbred with humans by sequencing the genomes of every human population. Look for sequences that seem out of place. Super cheap DNA sequencing will make that possible. What secrets lurk in the genes of Andaman Islanders, the Ainu of Hokkaido Japan, the Eskimos, or the Australian Aborigines?
Fossils of these Denisovans were found in a cave in Siberia.
The journal Nature reported the finding this week. The National Science Foundation's Behavioral and Cognitive Sciences Division partially funded the research.
An international team of scientists led by Svante Pääbo at the Max Planck Institute of Evolutionary Anthropology in Leipzig, Germany, used a combination of genetic data and dental analysis to identify a previously unknown population of early humans, whom the researchers call "Denisovans." The name was taken from Denisova Cave in southern Siberia where archaeologists from the Russian Academy of Sciences recovered a bone in 2008.
The finger bone of a girl provided the needed DNA sample.
Genetic sequencing of DNA extracted from a finger bone of a 5-10-year-old girl from the cave revealed that she was neither Neanderthal nor a modern human, but shared an ancient origin with Neanderthals. The genetic analysis also showed she had a very different history since splitting from Neanderthals, the researchers concluded.
A tooth from the cave is unlike human teeth. But what about the total shape of the Denisovans? The obvious thing to try: Clone them in a human egg. If a bunch of them are brought back into existence will they start communicating with each other telepathically and try to take over the planet?
4 to 6 percent of the genes of the people of Papua New Guinea come from Denisovans.
Another type of analysis reported by the study's authors showed Denisovans contributed 4-6 percent of their genetic material to the genomes of present-day New Guineans. "They are ancestors of people in Papua New Guinea but not of the great majority of people in Eurasia," said David Reich, a geneticist at Harvard Medical School in Boston, who led the research's population genetics analysis.
Check out pictures of the tooth.
Update: Carl Zimmer's coverage in the New York Times includes someone way more knowledgeable speculating the same point as I guessed at above: there could be more interbreeding cases waiting to be found.
Dr. Bustamante also thinks that other cases of interbreeding are yet to be discovered. “There’s a lot of possibility out there,” he said. “But the only way to get at them is to sequence more of these ancient genomes.”
Is ancient genome sequencing the only way to discover evidence of interbreeding? These genetic sequences from distant relatives of humans don't stand out for other reasons? I would think whole chromosome sequencing might identify chromosomes that couldn't possibly have come from humans who left Africa in the last 100,000 years. No?
Update II: Some comments from Greg Cochran in a Gene Expression thread point out that even before the paper reported on above there were signs of homo erectus admixture in Melanesians.
There has for a long time been a suspicion that Australoids had erectus admixture.
I’ve also seen funny genetic anomalies that are probably due to this.
There were further hints this year. Long, looking at microsatellites, found evidence for one admixture that showed up in all Eurasians and another that showed up only in Melanesians. Moreover, Linda Vigilant (from Max Planck) found Long’s work interesting and said that it fit certain patterns they had seen in Melanesians. Later, in the fall, I noticed the clues in Table S48. I thought that the Denisova sample might be from the same population (from Occam’s razor), but was somewhat discouraged from this when Paabo said the Denisova pinkie was Neanderthal, as recently as two weeks ago.
As for ancient population substructure in Africa – the idea that it explained the evidence of Neanderthal admixture was silly. The idea that it might explain Denisovan admixture in New Guinea is the turducken of silly.
I would expect some genetic differences in a human population can be too complex to be the product of that population's evolution by itself. If more such genetic signatures of admixture exist they will be found. The cost of genetic sequencing is getting too cheap for these patterns to remain undetected.
On Discover Magazine's GNXP blog Greg Cochran says the Denisovans are probably homo erectus.
“Unless of course you are suggesting that Denisovans=Asian Erectines??”
Of course I am. The dates in this paper are functions of the assumed mutation rate. We have two different estimates for that, one much-used standard rate based on essentially nothing, and a recent, much lower one one based on parent-offspring rates and known mutation rates for Mendelian diseases. In the paper, they used the standard rate. Switch to the lower rate and you get population split times that fit the fossil record better in both Europe and Asia.Yet it’s a great paper for all that.
Also see a post by John Hawks: The Denisova genome FAQ
HOUSTON -- (Aug. 17, 2010) -- The most robust statistical examination to date of our species' genetic links to "mitochondrial Eve" -- the maternal ancestor of all living humans -- confirms that she lived about 200,000 years ago. The Rice University study was based on a side-by-side comparison of 10 human genetic models that each aim to determine when Eve lived using a very different set of assumptions about the way humans migrated, expanded and spread across Earth.
The research is available online in the journal Theoretical Population Biology.
"Our findings underscore the importance of taking into account the random nature of population processes like growth and extinction," said study co-author Marek Kimmel, professor of statistics at Rice. "Classical, deterministic models, including several that have previously been applied to the dating of mitochondrial Eve, do not fully account for these random processes."
It speaks to the speed of human evolution that we've been able to generate so much genetic diversity in just 200,000 years.
In our future we will create new species out of genetic pieces of existing species. Some of these species might some day challenge us for dominion over planet Earth. Scientists have discovered a very small piece of human DNA which causes a big change in embryonic development of limbs in mice.
WALNUT CREEK, Calif.— Subtle genetic changes that confer an evolutionary advantage upon a species, such as the dexterity characteristic of the human hand, while difficult to detect and even harder to reproduce in a model system, have nevertheless generated keen interest amongst evolutionary biologists. In findings published online in the September 5 edition of the journal Science, researchers from the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) and their collaborators, have uncovered a specifically human 13-nucelotide change concealed in the vast three-billion-letter landscape of the human genome. Their experiments reveal this stretch of DNA to be a recently evolved regulator of gene expression that, when introduced into a mouse embryo system, influence the molecular machinery to yield human limb and thumb development patterns.
Some argue that genetic differences between humans are inconsequential because these differences make up such a small percentage of our total genome. But that a mere 13 genetic letters could cause mouse embryonic development to go down a pathway more like human limbs testifies to the power of small genetic sequences and small genetic differences. Also, that a group of scientists could fish this 13 letter sequence out of 2.9 billion letters in an entire human genome speaks to the power modern genetic analysis informed by an understanding of evolutionary theory.
The study reinforces the conclusion that certain regions of genomes—those which are conserved across many species over evolutionary time and do not encode genes—can have a powerful regulatory influence on gene expression or the production of proteins.
These scientists are looking for the genome differences that drove the split between primates and non-primates as well as the genetic differences that make humans unique from other primates in various ways. All these differences become candidates to stick into a transgenic dog or cat of course.
"The study points to how human nucleotide substitutions can alter the regulation of genes in humans distinct from that of non-human primates, such as chimps," said one of the study's corresponding/senior authors Eddy Rubin, Director of Berkeley Lab's Genomics Division and the U.S. Department of Energy Joint Genome Institute. "This highlights a strategy that could be applied across the genome to understand at a molecular level what leads to differences between humans and non-human primates."
These big comparisons between many species are made possible by the rapid decline in DNA sequencing costs. That decline is only going to continue. So the flood of data that makes cross-species comparisons possible will only increase as will the sophistication and power of the software and computers that do the comparisons. Therefore this discovery is just the opening of a flood gate. We will see many more such discoveries in the coming months and years.
Previously published work from the Rubin lab by co-authors Shyam Prabhakar (now at the Genome Institute of Singapore), James Noonan (now at the Yale University School of Medicine), and postdoctoral fellows describes a global survey they conducted of genomes—human, chimpanzee, rhesus macaque, mouse, rat, and dog. They screened across these species to find the most conserved regions, but where humans had many more changes relative to the others. By comparing the occurrence of these features, they were seeking to home in on evidence of positive selection—sequence changes that evolve more rapidly since the human and chimp paths split six million years ago.
The ability to do comparisons across species will also turn up genetic sequences in other species that give them features and capabilities that some humans will find appealing. Look at the people who go in for heavy plastic surgery, tattooing, and drug-enhanced muscle building. Imagine what those people will do once they can put genes into themselves from other species so that they can see better at night or hear better at high frequencies. If Fido and Rover can hear a dog whistle then why can't I?
Caveat: These results are preliminary. These scientists haven't proven that this short sequence really serves a role in humans similar to what it appears to do in mice.
Using mouse embryos, Noonan and his collaborators examined how HACNS1 and its related sequences in chimpanzee and rhesus monkey regulated gene expression during development. The human sequence activated genes in the developing mouse limbs, in contrast to the chimpanzee and rhesus sequences. Most intriguing for human evolution, the human sequence drove expression at the base of the primordial thumb in the forelimb and the great toe in the hind limb. The results provided tantalizing, but researchers say preliminary, evidence that the functional changes in HACNS1 may have contributed to adaptations in the human ankle, foot, thumb and wrist-- critical advantages that underlie the evolutionary success of our species.
May 6, 2004— Hundreds of stretches of DNA may be so critical to life's machinery that they have been “ultra-conserved” throughout hundreds of millions of years of evolution. Researchers have found precisely the same sequences in the genomes of humans, rats, and mice; sequences that are 95 to 99 percent identical to these can be found in the chicken and dog genomes, as well.
Most of these ultra-conserved regions do not appear to code for proteins, but may instead play a regulatory role. Evolutionary theory suggests these sequences may be so central to mammalian biology that even small changes in them would compromise the animal's fitness.
Led by Howard Hughes Medical Institute investigator David Haussler, at the University of California at Santa Cruz, the researchers published their findings online May 6, 2004, in Science Express, the Web counterpart of the journal Science. The lead author on the paper was Gill Bejerano in Haussler's laboratory. Also co-authoring the paper were John Mattick and his colleagues from the University of Queensland in Australia.
The first indication of the existence of ultra-conserved sequence regions was found in the initial comparison of the human and mouse genomes. Previous estimates of the amount of the genome that was "junk DNA" or sequences that are unused turned out to be too high. The amount of conservation of sequence that was found suggested most of the genome that has functionality is not coding for proteins. This argues that the genome contains much more regulatory complexity.
According to Haussler, the researchers were launched on their analysis when initial studies hinted at major regions of conserved DNA sequences. “When we had compared the human and mouse genomes, we found that about five percent of each of these showed some kind of evolutionary selection that partially preserved the sequence,” he said. “We got excited about this because only about 1.5 percent of the human genome codes for protein. So five percent was about three times as much as one might expect from the standard model of the genome, in which it basically codes for proteins, with a little bit of regulatory information on the side, and the rest is nonfunctional or “junk” DNA.
“These initial findings suggested that quite a lot of the genome was performing some kind of regulatory or structural role - doing something important other than coding for proteins,” said Haussler.
Comparison between the genomes of humans, mice, and rats showed many identical sequences. Most of those sequences do not code for proteins. So they are probably regions that regulate expression and translation of genes into proteins.
The comparison of the three genomes revealed 481 such elements that they called “ultra-conserved.” “What really surprised us was that the regions of conservation stretched over so many bases. We found regions of up to nearly 800 bases where there were absolutely no changes among human, mouse and rat.”
Although 111 of these ultra-conserved elements overlapped with genes known to code for proteins, 256 showed no evidence that they overlap genes, and another 114 appeared inconclusively related to genes. In the 111 that overlapped genes, relatively small portions were actually in coding regions. Many were either in untranslated regions of the gene's messenger RNA transcript or in regions that are spliced out before the message is translated into protein.
Many of the complex regulatory mechanism were worked out into their final form at least 300 million years ago. Some of our components are based on very old and proven designs.
“What really surprised us was that when we included the chicken genome in this comparison, we found that nearly all these regions still showed amazingly high levels of conservation,” he said. “In 29 cases it was 100%. This, despite the fact that the common ancestor of chickens, rodents, and humans is thought to have lived about 300 million years ago,” he said.
However, the researchers found these regions to be significantly less conserved in the genome of the fish called fugu. And when they extended their comparisons to the even more ancient genomes of the sea squirt, fruit fly and roundworm, they found very little evidence of these conserved elements. The sea squirt exhibits a simple spinal cord early in its life cycle, and so it is more closely related to vertebrates than are flies or worms.
“The most exciting thing for me is that the ultra-conserved regions we have identified do represent evolutionary innovations that must have happened sometime during vertebrate development, because we see such large pieces that no longer match in fish, and almost nothing in sea squirt. They must have evolved rather rapidly while our ancestors were still in the ocean, with some further evolution when animals first started to colonize land; after that they must have essentially frozen evolutionarily.
“This suggests that these were foundational innovations that were very important to the species, and since the conserved elements are different from one another, that each one was important in some particular way. It is possible that further innovations in other interacting elements created so many dependencies that these foundational elements couldn't be mutated any more without disrupting something vital,” said Haussler.
Comparative genomics is turning out to be incredibly useful. Conservation of regions shows which regions are functionally important. The higher the degree of conservation the more likely that a region is involved in some function that is heavily intertwined with many aspects of cellular function or development. Faced with billions of letters of DNA sequence information about conservation of sequences allows scientists to sort through and rapidly choose much smaller key sections for further study.
Comparative genomics is also incredibly useful between humans in part because it allows us to identify where selective pressures were acting on the genome. There are millions of DNA sequence differences between humans. Most have no effects. But others will turn out to be incredibly important for disease risks, differences in rates of aging, intelligence, personality, physical appearances, strength, and other characteristics.
The rate of discovery from comparative genomics is going to continue to increase quite dramatically in the coming years because of declining costs for DNA sequencing and SNP testing.
The argument that humans are evolutionarily maladapted to urban lifestyles and fast food finds support in a report that black bears are becoming fat and lazy from eating junk food from dumpsters.
NEW YORK (Nov. 24) -- Black bears living in and around urban areas are up to a third less active and weigh up to thirty percent more than bears living in wild areas, according to a recent study by scientists from the Bronx Zoo-based Wildlife Conservation Society (WCS).
The study, published in the latest issue of the Journal of Zoology says that black bears are spending less time hunting for natural food, which can consist of everything from berries up to adult deer. Instead, they are choosing to forage in dumpsters behind fast-food restaurants, shopping centers, and suburban homes, often eating their fill in far less time than it would take to forage or hunt prey.
"Black bears in urban areas are putting on weight and doing less strenuous activities," said WCS biologist Dr. Jon Beckmann, the lead author of the study. "They're hitting the local dumpster for dinner, then calling it a day."
In addition, the authors say that urban black bears are becoming more nocturnal due to increased human activities, which bears tend to avoid. Bears are also spending less time denning than those populations living in wild areas, which the authors say is linked to garbage as a readily available food source.
The authors suggest that as humans continue to expand into wild areas, and as bears colonize urbanized regions, people must be educated to reduce potential conflicts. Local ordinances should be passed mandating bear-proof garbage containers for homes and businesses. "Black bears and people can live side-by-side, as long as bears don't become dependent on hand-outs and garbage for food," Beckmann said. "Lawmakers should take a proactive stance to ensure that these important wild animals remain part of the landscape."
This change in environment is a selective pressure. While is it not clear what traits are being selected for in bears by urban environments it seems very likely that different traits are being selected for among urban bears than among bears that live out in the wild.
Update: I know what you are all thinking: In the face of the rising obesity of our inner city black bear population no government agencies or health professionals are taking steps to encourage the urban black bears to come to cholesterol screening clinics to see if their junk food diets are putting them at risk for heart disease. Even if they come to the clinics they have no medical insurance that includes a prescription drug benefit to pay for Lipitor. Something must be done. Also, are any black bears getting screening for type II diabetes? And who, if anyone, is giving them dietary advice? They need nutritional counseling and they should be on a diet high in fiberous nuts and berries. Shouldn't the junk food industry be taxed for making cheap high calorie meals so easily available in dumpsters?
Species that replicate at a slower rate and that are fewer in number do not experience enough selective pressure to prevent junk DNA from accumulating
Genetic mutations occur in all organisms. But since large-scale mutations -- such as the random insertion of large DNA sequences within or between genes -- are almost always bad for an organism, Lynch and University of Oregon computer scientist John Conery suggest the only way junk DNA can survive the streamlining force of natural selection is if natural selection's potency is weakened.
When populations get small, Lynch explained, natural selection becomes less efficient, which makes it possible for extraneous genetic sequences to creep into populations by mutation and stay there. In larger populations, disadvantageous mutations vanish quickly.
Most experts believe that the first eukaryotes, which were probably single-celled, appeared on Earth about 2.5 billion years ago. Multicellular eukaryotes are generally believed to have evolved about 700 million years ago. If Lynch's and Conery's explanation of why bacterial and eukaryotic genomes are so different is true, it provides new insights into the genomic characteristics of Earth's first single-celled and multicellular eukaryotes.
A general rule in nature is that the bigger the species, the less populous it is. With a few exceptions, eukaryotic cells are so big that they make most bacteria look like barnacles on the side of a dinghy. If the first eukaryotes were larger than their bacterial ancestors, as Lynch believes, then their population sizes probably went down. This decrease in eukaryote population sizes is why a burgeoning of large-scale mutations survived natural selection in the first single-celled and multicellular eukaryotes, according to Lynch and Conery.
To estimate long-term population sizes of 50 or so species for which extensive genomic data was available, Lynch and Conery examined "silent-site" mutations. Silent-site mutations are single nucleotide changes within genes that don't affect the gene product, which is a protein. Because of their unique characteristics, silent-site mutations can't be significantly influenced by natural selection. The researchers were able to calculate rough estimates of the species' long-term population sizes by assessing variation in the species' silent-site nucleotides.
Of the original group of sampled organisms, Lynch and Conery selected a subset of about 30 and calculated, for each organism, the number of genes per total genome size as well as the longevity of gene duplications per total genome size. They also calculated the approximate amount of each organism's genome taken up by DNA sequences that do not contain genes.
The researchers found that a consistent pattern emerged when genomic characteristics of bacteria and various eukaryotes were plotted against the species' total genome sizes. Bigger species, such as salmon, humans and mice, tended to have small, long-term population sizes, more genes, more junk DNA and longer-lived gene duplications. Almost without exception, the species found to have large, long-term population sizes, fewer genes, less junk DNA and shorter-lived gene duplications were bacteria.
The data suggest it is genetic drift (an evolutionary force whose main component is randomness), not natural selection, that preserves junk DNA and other extraneous genetic sequences in organisms. When population sizes are large, drift is usually overpowered by natural selection, but when population sizes are small, drift may actually supersede natural selection as the dominant evolutionary force, making it possible for weakly disadvantageous DNA sequences to accumulate.
Junk DNA costs energy to duplicate and to carry around as part of each cell. So natural selection operates against it. But if junk DNA gets generated by errors in replication faster than natural selection can select against it then junk DNA can accumulate..
At some point in the 21st century, barring some natural or human-caused disaster, biotechnology will advance far enough to make it possible to edit out junk sequences from cells. So it should become possible to have offspring that have far fewer junk DNA sequences. Therefore junk DNA may eventually disappear from the human species. Also, replacement organs will eventually be genetically enhanced with more beneficial variants of genes that play important roles in each organ type. It seems reasonable to expect that at least some people will opt to have their DNA edited to eliminate junk DNA sequences from cells that will be used to grow replacement organs. So even some of us who today are walking around with junk DNA will have less of it once we are able to have replacement organs grown for us.
Update: Carl Zimmer raises a number of specific objections against the idea of removing junk DNA but he also sees one point in favor of doing so: some junk DNA sections can hop around the genome and cause mutations when they embed in new locations.
There are also arguments for getting rid of junk DNA that Futurepundit doesn't mention. When mobile elements jump around to new homes, they can trigger diseases as they mutate the genome.
As for mobile elements that jump around the genome: Yes, note that this reason for removing junk DNA is especially strong in the case of stem cells that are going to be used to grow replacement organs. The cells in those replacement organs (with the exception of testes and ovaries) are not going to have their DNA passed along to progeny and therefore the ability of their junk DNA to mutate to create new environmental adaptations provides no benefit while the junk DNA does pose a mutational threat that can result in cancer and other diseases.
The effects of removing various junk sequences will be testable by producing organs without them and then seeing how those organs perform. This will be relatively less risky to experiment with in the case where humans have two of an organ. So, for instance, one could have just one kidney replaced with a junk-free kidney and then, with the other kidney still available as back-up, the functionality of the junk-free kidney could be monitored over time. The same could be done with many muscles. Replace a thigh muscle with a junk-free thigh muscle. If the thigh muscle fails the result is unlikely to be fatal. There would still be risks from such an experiment as one could imagine fatal failure modes where, for instance, an organ releases toxins or clotting factor or something else that damages some other more critical part of the body.
Next he raises the point that what seems like junk DNA might not really be junk DNA.
Junk-free genomes may indeed become possible in the future, but they're probably not a wise idea. Even if junk DNA doesn't benefit us in any obvious way, that doesn't mean that we can do without it. Many stretches of DNA encode RNA which never become proteins, but that doesn't make the RNA useless--instead, it regulates the production of other proteins. Some broken genes (known as "pseudogenes") may no longer be able to encode for proteins, but they can still help other genes produce more of their proteins
Well, my response to this is pretty simple: Yes, it is hard to be certain that some DNA section has no benefit to the cell. But suppose at some point in the future we can assign a really high probability to the idea that some chunk of DNA has no value and that it actually is far more likely to cause disease than benefit? Why not then remove it?
This reminds of another point: Some genetic theorists make the argument that we each have dozens and perhaps hundreds of purely harmful mutations because natural selection can't select out hamful mutations as fast as they are generated by mutations that occur during reproduction. If this argument is correct (and I believe it is) then we should also have junk DNA that is either of no value or harmful. Someone who holds this more pessimistic view of our genomes as full of flaws and parasitic DNA sections is going to tend to be more willing to decide to throw out the suspected junk with the view that the odds are great that the suspected junk really is junk. Of course, there's no rush here and we ought to wait a couple of decades for a lot more evidence to accumulate before acting on this belief.
Zimmer also brings up the argument that simply by making the genome bigger that junk DNA may serve a useful function by making cells the correct size. I'm skeptical of this argument mostly because an assortment of different kinds of intracellular components cross-react with each other in undesirable ways and turn into compounds that the cell can not eject or destroy. As a result, cells accumulate junk and this junk accumulation robs the cells of needed space and decreases the efficiency of cells as they age as well. The junk also serves as a source of free radical generation. This problem with junk accumulation has even led Aubrey de Grey to argue for the transfer of lysosomal enzymes from other species into humans as a rejuvenation treatment. Analogously, genomal junk is taking up space that could be used by cells to do useful work. Get rid of it and the cells might become ever so slightly more efficient.
Next Zimmer brings up the value of junk DNA and, in particular, pseudogenes, as potential sources of future beneficial mutations:
It's on this evolutionary scale where purging junk DNA makes the least sense. The pasting and copying of junk DNA is a major source of new genetic variation. Instead of changing a nucleotide here or there, mobile elements can shuffle big stretches of DNA into new arrangements, taking regulatory switches and other genetic components and attaching them to different genes. While some of this variation may lead to diseases, it also prepares our species to adapt to new environmental challenges. (Similarly, pseudogenes that are truly broken still have the potential to become working genes again. Some scientists have proposed calling them "potogenes.")
Here's my problem with that argument: Natural selection is going to cease to be the major source of new beneficial mutations in humans within 20 or 30 years. We are going to have our genomes changed by bioengineering. Therefore junk DNA will have no value to us. Going into future centuries our bioengineering techniques will advance even further and we will be able to simulate the effects of variations orders of magnitude more quickly than mutations occur naturally.
There's another point about junk DNA that especially holds for agricultural plants and animals: to the extent that junk DNA can be removed from crops and livestock a source of variability is removed that essentially serves as noise. If someone develops some ideal dairy cow and wants to clone it he does not want jumping genes creating variations that cause some of them clones to produce less milk. Similarly, jumping genes could create variations in the growth of corn or wheat that would be undesirable.
It should be possible to grow up replacement organs in other species first and to try out junk removal in organs and whole genomes in other species before trying it out in humans. This will provide an important way to discover functional purposes served by parts of genomes that are mistakenly thought to be junk. The mechanisms by which those parts serve useful functions will then be able to be searched for in humans as well. In my view, the discovery of which sections of the genome really are junk is a technical challenge that will be solved with time. Once purely junk sections are identified with a fairly high probability of correct classification and techniques for removing it are developed it seems inevitable that more daring individuals will opt to try to have the junk removed from their replacement organs and progeny.