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paleoanthropology, genetics and evolution

introgression

  • Another diagnosis for a hobbit

    Tue, 2007-07-03 12:18 -- John Hawks

    Israel Hershkovitz, Liora Kornreich, and Zvi Laron think they know the problem with Liang Bua 1. Almost 40 years ago, Laron began studying patients with a congenital deficiency of IGF-I (insulin-like growth factor, I). This deficiency occurs because of a defect to the growth hormone receptor, which then does not respond to growth hormone (GH). Hence, patients have a high circulating level of GH, but a low level of IGF-I. After Laron's description, this type of dwarfism was called Laron syndrome, or "Laron-type dwarfism". Since 1970, the disorder has been identified in families throughout the world, caused by a large variety of mutatations to the GHR gene. Much of this is reviewed in OMIM.

    In the last few decades, a large number of clinical cases of Laron syndrome have been compiled. Hershkovitz, Kornreich, and Laron (2007) review the characteristics of the LS sample. Patients were dwarfed -- significantly short in stature for their age -- by more than 4 standard deviations (SD) below the average for their population. Moreover, they had small endocranial volumes, as much as 5 SD below the average for their population.

    Here, I have reproduced Table 1 of the paper, including the list of similarities between Laron syndrome patients and the LB 1 skeleton:

    There are two notable features of this list, besides its sheer length. First, it includes characters from around the skeleton. This is the first substantial examination we have seen of the LB 1 features that compare the full body to the effects of any kind of human dwarfism. Evidence from the postcrania are especially important, because they form a constellation that may be the result of a common developmental cause. Second, the list includes a broad range of features that are not "outside the range" of modern human variability -- the kinds of rare features that a clinician would recognize as symptomatic in combination with other features, but that by themselves may be found within otherwise normal humans.

    If you've been following closely, you may remember that Richards (2006) also proposed that the features of LB 1 might be explained by a mutation to the IGF-I pathway, possibly in combination with other changes affecting brain size. Richards pointed out that pituitary dwarfism, including Laron syndrome, may alter the proportions of the limbs in a way similar to LB 1, and I view that as an important conclusion of the current paper (Herskovitz et al. 2007) as well. In fact, Hershkovitz and colleagues argue that many of the purportedly "unusual" features of the skeleton are straightforward consequences of its small size. This includes not only the proportions of the limb bones, but other details such as their slight muscle markings.

    Interestingly, the low humeral torsion of LB 1 also figures into the LS diagnosis, and they spend nearly a page reviewing this feature. The torsion increases with age up to around 16, and developmental abnormalities including LS may cause it to fall below the general adult range. But this has become a very equivocal feature. Larson and colleagues (2007) reported that the humeral torsion exhibited by LB 1 was within the range of contemporary Australians. There's a huge range of torsion included within normal human populations, now -- extending as low as macaque values. The more comparisons are included, the more the LB 1 specimen seems to fall in the human range. This is not too surprising; if every unusual skeleton could be diagnosed by comparison with a small number of specimens, there would be no need for pathologists!

    Brain size

    Richards (2006) considered Laron syndrome briefly, but concluded that Laron syndrome patients have a cranium that is "near-normal in size." In the present paper, Hershkovitz et al. claim that the brain size is reduced by "up to 5 SD" in Laron syndrome. What gives?

    Here is the relevant text from Hershkovitz et al.:

    There is no doubt that the most striking characteristic of LB1 is not small stature but rather the minute cranial capacity. Despite the fact that the cranial volume in patients with LS is usually not decreased to the same degree as observed in LB1, three points should be mentioned: a) skulls of LS patients manifest most of the unique LB1 cranial features, b) a small head is a major characteristic of LS patients (up to 5 SD below the norm) and in IGF-I gene deletion (Woods et al., 1996). Jacob et al. (2006) reported that the LB1 cranial volume falls 5.5 SD below the combined sex Rampasasa mean, similar to what has been reported for LS patients, and c) there is a high degree of association between microcephaly and growth failure in general (O’Connell et al., 1965; Pryor and Thelander, 1968), GH deficiency (Dacuo-Voutetakis et al., 1974), and congenital IGF-I deficiency (Laron et al., 1968; Woods et al., 1996) in particular.

    Additionally, many of the unique anatomical landmarks left by the brain of LB1 on the endocranial bony surface (Falk et al., 2005), are seen also in LS patients, and derived from the reorganization of the brain to fit into a small cranial space... (Hershkovitz et al. 2007:7).

    Additionally, they point out that the genetic background of their sample of LS patients is different from that of recent and archaeological Southeast Asian islanders, which may also produce differences in the manifestation of growth deficiencies.

    Is this fully convincing? The radiographs in the paper do not show skulls as reduced in cranial volume as LB 1. As far as I know (they do not present a range) there are none. Perhaps Richards (2006) is correct that a second explanation is necessary besides GH/IGR-I to explain the small brain, or perhaps the manifestation of such disorders in this population really is different. Plausibly, an archaeological specimen from anywhere is simply not comparable to the development of modern agricultural populations. I think the brain size remains a big hole in the hypothesis.

    The hypothesis is testable!

    The best thing about the LS hypothesis is that it is testable. There are other features of the skeleton that reflect LS that have not yet been reported for the LB 1 skeleton, but that ought to be observable.

    Hershkovitz et al. (2007) point to the pneumatization of the mastoid region as possibly the most important test. LS patients have minimal or no pneumatization of this part of the cranial base; meaning that instead of spongy bone and open sinuses, they have dense compact bone:

    Unfortunately, no radiographs of LB1's skull are as yet available and therefore appreciation of the extent of pneumatization in the LB1 skull is impossible. Non-pneumatized (acellular) mastoid process (Fig. 4), lack of (or minimal) frontal sinus (Fig. 2), and small paranasal sinuses are characteristic of LS (Kornreich et al., 2002) (Hershkovitz et al. 2007:3).

    CT scans of LB 1 do exist, and they should be easy to check. Very easy. As in, somebody already knows the answer. That somebody just isn't me.

    But is it a species?

    What would it tell you if the hypothesis were true -- if LB 1 actually does have a mutation inducing a GH/IGR-I defect and this explains its stature, morphology, and brain size? For instance, does it represent a real ancient hominid species or just a pathological member of our own?

    Hershkovitz, Kornreich, and Laron agree with Jacob et al. (2006), that many of the "unusual" characteristics of the skeleton actually are normal or reasonably common within the regional population of modern humans. For that reason, they find that the skeleton possesses no features that preclude it from membership in our species. So the short answer is, they think H. floresiensis is sunk.

    But their longer answer is quite interesting as a defense of taxonomic conservatism, and is worth reading closely:

    It is not the numerous conundrums that have been located by us and other researchers (Jacob et al., 2006; Martin et al., 2006a,b) in the Homo floresiensis publications which refute its status as a new species, but rather the wrong arguments brought to support it.

    The combination of "modern" and "primitive" morphological characteristics is one of the major arguments raised by Brown et al. (2004) to differentiate LB1 from Homo sapiens. Nobody would argue, however, that LS patients who also manifest a similar combination (e.g., an extremely oval-shaped pelvic inlet, or a "bell-shaped" form of the thoracic cage), are direct descendents of Homo erectus (an idea advocated strongly for LB1 in the first paper) nor of the australopithecines (a notion which appears in the second publication). Based on morphological comparison between LS patients and normal short children, it is clearly evident that many of the "unique" primitive morphological traits seen in LB1 are due to her small stature (Takano et al., 1986). This also explains why LB1 shares most of her features, including the most "unique" ones (e.g., the deep fissure separating the mastoid process from the petrous crest of the tympanic bone; the absence of a true chin etc.) with local pygmoid populations (Jacob et al., 2006). Ignoring the possibility that LB1 is derived from a small stature population (Rampasasa pygmies are good candidates, as suggested by Jacob et al. in 2006) with its own distinct morphological features may lead to erroneous conclusions. For example, recently Larson et al. (2006) reported on a clavicle (short relative to humeral length) and scapula (normal) of LB1 and suggested that "A short clavicle may indicate a more protracted scapular position, raising the possibility of a previously unsuspected transitional stage in the course of hominin pectoral girdle evolution" (p A21). However, the length of the clavicle is mainly dictated by the shape and diameter of the upper thoracic cage. This is why both LS patients and KNM-WT 15000 H. erectus (both manifesting a very similar fan-shaped thorax) have a relatively short clavicle.

    In contrast to Morwood's statement (2005) that LB1 manifests a combination of primitive and derived features that dictate exclusion from the species sapiens, we have herein offered evidence to suggest that LB1 is but a local individual in a highly inbred, probably pygmy-like population (of Homo sapiens) in whom a mutation of the GH receptor had occurred. (Hershkovitz et al. 2007:9).

    In short, the persuasiveness of any combination of features as evidence depends on their correlation with each other. If they are all strongly correlated -- for instance, if they are effects of a common cause -- then the combination of features is best interpreted as evidence for that cause, rather than as multiple instances of evidence for some other hypothesis. In this case, Hershkovitz et al. argue that the common cause explaining the data does not require a species interpretation. Instead, they argue (following Jacob et al. 2006) that LB 1 and other specimens share many features with recent local people. So, the hypothesis that the LB hominids are Homo sapiens is well supported.

    Now, what could contradict that hypothesis? In other words, what would be the right argument to support a new species?

    Here, the morphology of the other specimens besides LB 1 come into play. It seems very unlikely that multiple archaeological individuals over many thousands of years would have had the same rare mutation(s) of the GH/IGR-I axis unless that mutation were very common in the local population. Richards (2006) accepted at face value the argument that these archaeological individuals were in fact of the same short stature and small size as LB 1, and suggested that the ancient Flores population of H. sapiens simply had a high frequency of this variant (in his view, possibly along with another variant affecting brain size). Hershkovitz and colleagues appear willing to accept this hypothesis, pointing out that LS patients have normal reproductive potential and are relatively more common in some populations:

    As LB1 replicates most of the diagnostic features of LS patients (Table 1), as well as those of pygmoid Australomelanesians (Jacob et al., 2006), it can be assumed that the findings from the island of Flores represent a local, highly inbred, low stature Homo sapiens population in whom a mutation in the GH receptor had occurred. The long time presence of LB1-type humans on the island of Flores is not surprising considering that LS patients, and derived dwarfed populations with GHRH-R defect, reproduce normally (Laron, 2004) (Hershkovitz et al. 2007:9).

    But it is not necessary to take this view of a long-term population with a variant GH/IGR-I allele, if the other specimens are not actually unusual for modern humans. That is the argument put forward by Jacob et al. (2006), and it doesn't yet seem to have been contradicted. The most persuasive commonalities among this collection of fragments are (1) that they are all small, and (2) that the second mandible LB 6/1 shares several features with the first. But Jacob et al. (2006) claim (1) that the local population was small anyway, and (2) that these features are regionally common and not persuasive as evidence for a distinct lineage.

    An alternative claim might be that H. floresiensis was a genuine evolutionary species on Flores (and possibly other islands), and that local people today retain features from this ancient species due to local introgression. But of course, local ancestry of some features might occur whether the ancient Flores population was another species or not. We call the latter hypothesis "multiregional evolution." So any distinctiveness of the local people is in no respect evidence that ancient people on Flores were a different species; if anything, the long-term retention of local features into living populations is a refutation that they were a different species. There is nothing impossible about introgression -- as I've said many times -- but it actually is a bit easier if speciation has not occurred!

    Picky details

    As in many clinical descriptions of dwarfism, there is a lot of "SD" talk in this paper. That substitutes an absolute measure (e.g., meters) for a relative one (compared to the population variability). And in some ways, that confounds two different kinds of change. For example, after a very good discussion of the problems estimating proportions and stature of LB 1, the paper includes this:

    Finally, Jacob et al. (2006) estimated that the stature of LB1 falls 3.3 SD below the local Rampasasa pygmy average stature of 1.46 m, within the range of the deviation in stature reported in some of the Israeli LS patients (Laron, 2004).

    This is not really a valid comparison. If pygmy populations of humans already have a variant of the GH/IGF-I axis that results in reduced stature, then a further mutation on that axis should not exert the same proportional effect. We ought to expect a dwarf in a population of pygmies to be close to the stature of dwarfs elsewhere.

    Instead, the important comparison is the stature itself, not the number of standard deviations below mean. Hershkovitz et al. (2007) report that the stature of female Laron syndrome patients in their sample ranges as low as 95 cm, which is smaller than the minimum stature estimate of 106 cm for LB 1. Hence, it is consistent with the diagnosis.

    Also, the genetic heterogeneity of LS means that there can be substantial variations among people with different mutations:

    So far 57 mutations have been described in LS patients residing in various parts of the world including South Asia (Rosenfeld et al., 1994; Rosenbloom and Guevara-Aguirre, 1998; Laron, 1999; Shevah et al., 2005). These numerous molecular defects on the GH receptor gene or the postreceptor cascade (Elders et al., 1973; Godowski et al., 1989; Laron et al., 1992; Rosenbloom et al., 1999; Laron, 2004; Woods and Savage, 2004) produce a large variety of short stature phenotypes and a wide spectrum of intellectual abilities and deficits (Shevah et al., 2005), which may also explain the differences between the LS patients and LB1 (Hershkovitz et al. 2007:9).

    This is the kind of quote that can drive a person crazy. The disorder is genetically heterogeneous. As reflected in OMIM, it may even include individuals with normal GHR function, but with other downstream problems that decrease IGF-I. But it is unsatisfying because it means that no comparison can necessarily capture the effects of the disorder. So for something like the exceptionally small brain size of LB 1, it is quite possible to say, "Well, there are at least 57 different ways to have this disorder, and maybe the 58th will be manifested with even smaller brain size.

    On the other hand, with 57 different varieties (hmm....) we can probably say that the sample space of genetic mutations is now very large, so we are seeing possibly a good representation of the possible phenotypic effects of changes to this axis. At least, that's my optimistic answer.

    Summary

    This is a powerful paper. The overlap between the morphology of LB 1 and Laron syndrome symptoms is very extensive.

    To my mind, much of the credibility of the species hypothesis -- that H. floresiensis really existed on Flores for a long time and evolved a mean phenotype including derived features absent in other populations -- depends on finding more specimens from earlier time intervals. If the archaeology of the island could be extended into the period after 500,000 years, it would document the long-term persistence of some hominid population across the interval from 700,000 years ago to 90,000. At 90,000 years, given ambiguities in dating, it is entirely possible that remains may be attributed to modern humans. So documenting a persistence in between those dates is important.

    Likewise, the anatomical evolution of those populations would be a key piece of evidence. Were they, as Jacob et al. (2006) suggest, connected by gene flow to the Asian landmass by recurrent connections? Or were they really isolated on Flores or possibly other islands? Only a trace of the evolutionary history, through morphology or DNA, can provide evidence of this isolation.

    I don't view any of this as impossible, but naturally it remains to be demonstrated. Likewise there is nothing impossible about such a population having a unique GH/IGR-I variant, either by drift or as an adaptation to the island. But we are waiting for the evidence that they were there throughout that time.

    References:

    Hershkovitz I, Kornreich L, Laron Z. 2007. Comparative skeletal features between Homo floresiensis and patients with primary growth hormone insensitivity (Laron Syndrome). Am J Phys Anthropol (early) doi:10.1002/ajpa.20655

    Richards GD. 2006. Genetic, physiologic and ecogeographic factors contributing to variation in Homo sapiens: Homo floresiensis reconsidered. J Evol Biol 19:1744-1767. doi:10.1111/j.1420-9101.2006.01179.x

    Jacob T, Indriati E, Soejono RP, Hsü K, Frayer DW, Eckhardt RB, Kuperavage AJ, Thorne A, and Henneberg M. 2006. Pygmoid Australomelanesian Homo sapiens skeletal remains from Liang Bua, Flores: Population affinities and pathological abnormalities. Proc Nat Acad Sci USA. 103:13421-13426. DOI link

    Tags: 
    Flores
    introgression
    Homo erectus
    multiregional

  • Global biopharming

    Fri, 2007-06-01 13:45 -- John Hawks

    Planting time has arrived in most of the country -- even here in zone 4 -- so you may be reading those seed packets carefully. This paragraph may catch your attention:

    One anti-biotech group even managed to bamboozle some seed companies that cater to home gardeners into signing on to something called the Safe Seed Pledge: "We pledge that we do not knowingly buy or sell genetically engineered seeds or plants." This is fascinating because, with the sole exception of wild berries and wild mushrooms, all the fruits, vegetables and grains in North American and European diets have been genetically modified or engineered by one technique or another. This even includes 'heirloom' varieties of fruits and vegetables. Often, this genetic modification has involved radical changes at the level of DNA, including the movement of genes or even entire chromosomes across natural breeding barriers.

    That's from a TCS Daily column by biotechnology analyst Henry Miller. This is a point that constantly amazes me -- do people not realize that it is unnatural to have purple potatoes and zebra-striped tomatoes, and all other manner of garden mutants? That, for the most part, it is unnatural for vegetables (i.e., non-fruit and non-seed plant parts) to be tasty and delicious? Plants don't want you to eat them!

    Most of the column is devoted to reviewing some of the misleading parts of a recent report on international biotechnology trends by the Organization for Economic Cooperation and Development. It's a fair critique, but a little dry for light reading. Certainly it's valuable to have critics go through definitions in these international reports, because so much of the conclusions are essentially determined by the assumptions that go into compiling lists. Some countries look different than others, just because their regulatory agencies define things in different ways.

    I approach this issue from the perspective of teaching the debate in my genetics course, and also as a way to examine how the debate around human genetic engineering may be framed in the future. After all, franken-people are bound to be a lot more interesting than franken-food.

    Not to mention the possibility of Neander-people -- or, dare I suggest, NEANDER-FOOD!

    I find the trend toward GMO production of pharmaceuticals to be a very interesting angle in the current biotechnology scene, because of the clear resonance of the issues with human genetic alteration. Both the opposition and promotion of GMOs have both involved heterogeneous groups of interests. Much of the muscle behind both positions has come from agriculture industry groups -- So far, the critics of GMO deployment have been successful when they frame their opposition in terms of risk of introgression into non-GMO crops or wild plants. They have also had success with the "natural food" frame.

    A month or so ago, I referred to an article that discussed the potential of introgression by plants genetically engineered to produce pharmaceutical compounds. Quoted in the article, Norman Ellstrand asked, why not modify non-food plants, and thereby eliminate all risk of consumption?

    In his article, Miller gives an answer to this question:

    Although there is substantial and growing acreage of gene-spliced crops cultivated worldwide each year - 252 million acres in 2006 - more than 90 per cent of it is four large-scale commodity crops; largely because of the huge costs of meeting regulatory requirements, the application of the technology to fruits, vegetables and subsistence crops has been minimal, and disappointing.

    In short, it is easier to get approval for altering one of the four major food crops, because they have a research history and are already grown on a immensely large scale. Introducing genetic modification on another kind of plant requires much more work to conform to regulations.

    There is also the issue of a less-recognized mode of genetic modification; namely, Simpsons-style:

    Currently, dozens of genetically improved varieties that are produced through hybridization, irradiation and other traditional methods of genetic improvement enter the marketplace and food supply each year without any governmental review or special labeling. A technique in use since the 1950s, induced-mutation breeding, involves exposing crop plants to ionizing radiation or toxic chemicals to induce random genetic mutations. These treatments most often kill the plants (or seeds) or cause detrimental genetic changes, but on rare occasions the result is a desirable mutation. For example, a mutation might produce a new trait in the plant that is agronomically useful, such as altered height, more seeds, larger fruit or enhanced resistance to pests.

    On a large scale, these random mutations pose more potential of introgressing into wild plants, because they don't carry the baggage of a plasmid, and they might have unknown beneficial side effects on plant fitness. Plus, a strain bearing many random mutations might have some unintended ones along with the one that is strongly selected by subsequent breeding. This kind of induced-mutation breeding is really nothing more than ordinary breeding sped-up a little faster, but then, the only thing making trans-species gene transfer different is that you know in advance that the inserted gene works in some other organism.

    In a previous column, Miller argued against legislation being considered to regulate the farming of gene-spliced plants in California. At the same time, he points out the harmful consequences that sometimes result from conventional breeding:

    This measure is pointless. In the production of new plant varieties using conventional - that is, pre-gene-splicing - techniques, breeders, farmers and food producers lack knowledge of the exact genetic changes that produced the useful traits. More important, they have no idea what other changes have occurred concomitantly in the plant -- including those that could alter the ability to cause allergic reactions.

    ...

    Only the molecular, gene-splicing methods allow breeders to identify and fully describe the changes that have been made in the progeny, so perhaps it isn't surprising that only the imprecise, trial-and-error techniques of conventional plant-breeding methods have led to food safety problems. Two conventionally bred varieties each of squash and potato and one of celery were found to contain dangerous levels of endogenous toxins and had to be barred from commercialization. Such mishaps are far less likely when genetic changes are wrought with the more precise and predictable gene-splicing techniques.

    The difference is not mainly that the trans-species genes are predictable in effect, but that they are introduced only a few at a time. This is less likely to cause incidental side effects than altering the frequencies of many genes by conventional breeding. The point is that anything that we change may generate bad side effects, and we want to find ways to minimize these. One approach is not to change anything. But since nature changes things for us anyway, maybe best to change with science...

    Tags: 
    agriculture
    introgression
    biotech
    Neandertals

  • No Neandertal in you?

    Fri, 2007-05-18 09:21 -- John Hawks

    Elizabeth Pennisi has a news article in today's Science with the headline, "No Sex Please, We're Neandertals." It covers a couple of talks by Svante Pääbo at a Cold Spring Harbor meeting.

    I'll get to the headline in a second; first I want to point out the more interesting paragraph at the end of the piece:

    In a side project, Pääbo and his graduate student Johannes Krause have examined 30,000- to 38,000-year-old human fossils from Uzbekistan and the Atlai region of southern Siberia whose identities were a mystery. When the researchers compared the bones' mitochondrial DNA with that from more than a half-dozen Neandertals, they found that the Asian fossils were clearly Neandertal. "It tells us that Neandertals were much more widespread than we thought," says Pääbo.

    It's not entirely unexpected that the biological population of central Asia was Neandertal-like during this time range; many researchers have long classified the Teshik-Tash child from present-day Uzbekistan as a Neandertal. I wouldn't go so far, but there are anatomical similarities between this specimen and European Neandertals that suggest gene flow right across central Asia.

    What's interesting about the mtDNA result is that the Neandertal mtDNA lineage is defined by a number of distinctive mutations, all of which took some time to occur on that branch. The variation within Neandertals so far is quite limited -- much like the variation within recent humans is limited. And the date of separation of the Neandertal and recent human clades is also relatively recent -- between around 350,000 and 700,000 years ago.

    So Neandertals were a population that was circumscribed to a small amount of mtDNA variation, like recent humans. This we already knew. But the large geographic extent of their mtDNA clade shows that they were a geographically widespread population -- from Spain to the border of China -- with a very small amount of mtDNA variation. Like recent humans.

    And like recent humans, relatively rapid genetic dispersals appear to have been possible over long distances. That's not the stereotype of Neandertal population dynamics we're used to reading.

    Now, about that interbreeding thing.

    In one of last fall's Neandertal genome papers, Green and colleagues (2006) reported that the putative Neandertal sequence included an unusually high number of human-derived SNPs -- that is, polymorphisms in humans where both the Neandertal and some humans carried a derived mutation, while other humans carried the ancestral nucleotide.

    These human-derived SNPs are important because they are likely to be relatively recent; and mutations that recently emerged in humans should be less likely to be found in a Neandertal. That is, unless Neandertals were interbreeding with the ancestors of living people. This isn't quite the same thing as Neandertals being the ancestors of living people; the comparison doesn't test for the direction of gene flow, which conceivably was one-way gene flow into Neandertals. Still, it was pretty striking evidence for Neandertal-human genetic interactions (as I pointed out in my FAQ post), if it was true.

    But there was some doubt about the conclusion of gene flow. For one thing, the sequence might be contaminated by DNA from a recent human. There still is no way to tell from these sequencing techniques whether a given fragment of DNA from the fossil is actually endogenous to the fossil, or whether instead it is a contaminating sequence from some living (or recently dead) person. There's still no solution to this problem, beyond the claim that the sequence contains a small proportion (maybe less than 6 percent) of mtDNA contaminant sequences from recent humans. But 6 percent contamination could put a lot of human-derived SNPs in the sample, making it look like gene flow existed where none actually did.

    The second reason for doubt was that databases of human SNPs are biased toward common alleles. That is, when people are looking for genetic markers (usually for medical research), they tend to exclude very rare polymorphisms and focus on ones where the alleles are nearer to 50 percent frequency. This is called an ascertainment bias. The bias is a problem for the Neandertal comparison because common alleles are more likely to be older than rare alleles. Which means that the human-derived SNPs in the human databases are probably somewhat older on average than theory would predict in the absence of this ascertainment bias.

    In other words, these human-derived SNPs are interesting because they ought to be recent, but in fact the sample of SNPs that we have is likely to be older than they ought to be.

    Now, this might make a difference to the hypothesis of Neandertal-human gene flow, or it might not. There is a pretty simple way to find out whether it makes a difference -- just work out the ages of the human-derived SNPs in humans.

    Apparently, this isn't what the research did. Instead, they decided to limit the human comparison to two individuals -- attempting to zero-out the ascertainment bias.

    So David Reich of Harvard Medical School in Boston and James Mullikin of the National Human Genome Research Institute in Bethesda, Maryland, have now compared SNPs in new Neandertal sequences to random SNPs obtained from one African and from one European. The result: "There's no indication of gene flow," Pääbo reported. Pääbo and his group got the same result when they examined variation in the Y chromosome, looking for signs of Homo sapiens DNA embedded in the Neandertal sequence.

    It may never be possible to prove beyond doubt that interbreeding did not occur. "But if I were to make a guess, I would say more sequence will just confirm [these results]," says Noonan. "It convinces me."

    The Y chromosome is expected; the recent human coalescent is so recent that a descendant sequence would be very unlikely to be found in this Neandertal.

    Much depends on how the "random" SNPs were obtained, so I can't evaluate until I see more details. For example, if they were obtained by resequencing the same million base pairs in two humans as has been recovered from the Neandertal sequence, that would probably work. On the other hand, if they were obtained by bootstrapping already-existing SNPs from two HapMap individuals ... well, that's probably not the best idea.

    And we are still left with the contamination problem. The thing is, contamination predicts that there ought to be an excess of these human-derived SNPs in the Neandertal sequence. Some of them should be in that sequence because of contamination, if for no other reason. So if they aren't finding any evidence of them in their comparisons, hmm...

    In any event, none of these comparisons really address the most likely reason for gene flow from Neandertals into recent humans (or vice versa), which is selection. If the number of introgressing genes was relatively modest, we wouldn't expect to see a large number of human-derived SNPs in the Neandertal sequence, even though the gene flow between the two populations was highly important to their fitness. I've gone into this before, and of course it was the subject of one of my papers last year.

    References:

    Pennisi E. 2007. No sex please, we're Neandertals. Science 316:967. doi:10.1126/science.316.5827.967a

    Tags: 
    Neandertals
    introgression

  • Notes on "Darwinian agriculture"

    Thu, 2007-04-19 12:26 -- John Hawks

    R. Ford Denison's blog, "This Week in Evolution," has become a very interesting read since he began a couple of months ago. Denison recently attended a symposium titled, "Darwinian Agriculture: the evolutionary ecology of agricultural symbiosis." He summarizes the basic idea of "Darwinian agriculture" in his pre-meeting post:

    "Darwinian Agriculture: when can humans find solutions beyond the reach of natural selection?" was the title of a paper that Toby Kiers, Stuart West, and I published in 2003. Our answers to the title question suggested how increased understanding of past and ongoing evolution could improve: 1) breeding of crops and livestock, and 2) design of agricultural ecosystems.

    With respect to genetic improvement of crop plants, we wrote:

    "most simple, tradeoff-free options to increase competitiveness (e.g., increased gene expression, or minor modifications of existing plant genes) have already been tested by natural selection. Further genetic improvement of crop yield potential over the next decade will mainly involve tradeoffs, either between fitness in past versus present environments, or between individual competitiveness and the collective performance of plant communities."

    Since then, every time I give a talk on this subject, I look for papers that might disprove this tradeoff hypothesis. I also look for examples of tradeoffs that were rejected by natural selection, but which might be acceptable in agriculture. For example, many people are working on improving drought tolerance of crops. Is it possible to improve on natural selection for this trait?

    In other words, the concept is something like the agricultural version of evolutionary medicine. The past is important to the present, and understanding how crop plants were selected in past environments (both natural and agricultural) helps us to predict the likely constraints on their current adaptive potential. Further, those constraints might be relaxed by trading off some traits that in the past may have been strongly selected, but at present are of less adaptive importance.

    Few people working to unravel evolutionary history stop to think about the practical implications of this research. And unfortunately, few people working in applied fields like agriculture or medicine think much about how knowledge about evolutionary history can be applied to modern problems. But this is changing -- more and more, it has become clear not only that the present is a product of the past, but also that the past helps to determine the future.

    A second post was a follow-up to the symposium, reviewing some of the papers presented. A couple of papers on genetic diversity in modern cattle and their relationships to European aurochsen are reviewed. These are very interesting, and of course Greg Cochran and I wrote a short review of this story in our introgression paper last year.

    Denison's quick review of his own presentation is a good illustration of conflicting selection in crop evolution, and attempts to reduce counterselection:

    Finally, I talked about breeding crops that yield more per acre (or hectare) because individual plants compete less with each other. The best-known example is plant height. Short plants make more grain because they waste less on stems. This works well if you have a whole field of short plants. But, in a mixture, the taller, low-yield plants shade out the shorter high-yield plants. Plants that branch less can yield more, in monoculture, but can't compete against plants that branch more.

    In this way, the unique practices that have helped to make agriculture such a productive system for humans can actually impede further response to selection -- as genetic variation within crop plants can include strategies that defy attempts to select for a given trait. It's game theory applied to corn! More to the point, selecting for short plants is an inefficient way to deal with the problem. Hybrids (and cloning) work as farming techniques not only because of overdominance, but also because making sure that your entire field is genetically uniform is a way of reducing the strategy options available to the plants.

    One of the papers also covered the ecology of a non-human agricultural analogue: ant fungus farming:

    In ant gardens, contact between two different fungal strains triggers a negative reaction that reduces growth. Even manure from ants that ate one strain will trigger this reaction in a second strain. In termite gardens, different fungal strains don't fight. But they don't bond, either, and this also limits growth. Over tens of millions of years, ants and termites have evolved behaviors that maintain their gardens as fungal monocultures. Ants remove alien fungi, even strains that might be grown by another ant colony. Termites prevent their fungi from reproducing sexually, by eating fruiting bodies that could produce sexual spores. Without sex, one strain gradually takes over.

    Now that's what you call selective breeding. Of course, they have the same aim as humans. The best way to maximize the energy return of the fungus is to eliminate the possibility that it can disperse without your help! If you don't want your domesticate to lose productivity to cheater strategies (which attempt to disperse on their own), then you had better cut off all possibility of gene flow into your fungus garden.

    Denison points out at the end of his post that this farming strategy itself is not always optimal:

    Whether we look at ant or termite fungus gardens, microbes that help crops, or crops themselves, diversity can lead to interactions that reduce growth. Should we work to reduce diversity in agriculture, then? Not exactly. Diversity may be useful at some scales, but harmful at others. If the world grew more different crops, a disease that killed any one crop would have less effect. But that may not mean that every field should contain more than one crop.

    Some of this confirms common sense -- Denison mentions crop rotation as a long-employed diversity management technique. But the details of the interactions of plant ecology, human management practices, and genetic correlations among different traits will be central to the future of agricultural science. It's a clear example of the practical importance of evolutionary theory.

    Related posts here:

    Roundup ready, a review of glyphosate resistance linking to a story on the emergence of coca plants resistant to Drug War-related herbicides.

    More on bison and introgression, a post covering attempts to breed cattle genes out of bison, and vice versa.

    The inevitability of introgression, covers my paper with Cochran.

    Breeding nutritional Neanderwheat, on the introduction of genes from wild wheat relatives into domesticated wheat.

    Tags: 
    introgression
    agriculture
    Neandertals
    Darwin

  • Plant drug introgression

    Mon, 2007-04-09 15:25 -- John Hawks

    This is a nice little article in the times by "collaborative problem solving" director Denise Caruso

    A NEW generation of genetically engineered crops that produce drugs and chemicals is fast approaching the market -- bringing with it a new wave of concerns about the safety of the global food and feed supply.

    The plants produce medicinal substances like insulin, anticoagulants and blood substitutes. They produce vaccine proteins for diseases like cholera, as well as antibodies against tooth decay and non-Hodgkin's lymphoma. Enzymes and other chemicals from the plants can be used for a range of industrial processes.

    As in past debates over genetically modified crops, biotech developers say that the benefits outweigh the risks, and that the risks are manageable. Critics question the benefits, and say the risk of a contaminated and potentially toxic food supply is untenable.

    Ellstrand was a good expert to interview -- I included several of his articles in my introgression bibliography -- and his points seem like the most relevant ones:

    "I don't think that engineering plants for pharma is a bad idea, with two caveats," Professor Ellstrand said. One, he says he thinks that planting should be done in greenhouses rather than in open fields. "The other issue is food," he said. "Why do we have to do this in food crops? It doesn't matter what you're squeezing the compound out of. It could be a carnation, a corn plant or a castor bean."

    That last seems like a good point: why not switchgrass or something? I suppose that the real answer to this question is that there is lots of farm equipment that is designed to deal with the seeds of existing agricultural crops, making the economics of these plants much more appealing than non-food plants. But there probably is some compromise crop that would suit this concern.

    Maybe they could find a way to make drugs in plants destined for ethanol -- two birds with one stone.

    Tags: 
    agriculture
    biotech
    introgression

  • Roundup® ready

    Sat, 2007-03-17 00:00 -- John Hawks

    Larry Moran posts on glyphosate resistance in weed plants:

    Roundup® (glyphosate) has been used to control weeds since 1974 [How Roundup® Works]. In all those years, the number of reported cases of resistant plants has been far below predictions. Only in the past ten years have Roundup®-resistant plants been identified and there are only 11 species of resistant weeds known at last count (Perez-Jones et al. (2007).

    We now know from studies of the mechanism of resistance of the C4 EPSP synthase that resistance to glyphosate requires very special circumstances; namely, an enzyme active site that can exclude glyphosate while still allowing phosphoenolpyruvate to bind efficiently [The Molecular Basis of Roundup® Resistance]. Thus, with hindsight, it is perhaps not surprising that so few resistant plants have turned up.

    This post and the earlier one outlining the biochemistry of glyphosate are very interesting to me (for reasons that will probably remain obscure!) and make a useful counterpoint to the more common tales of antibiotic resistance in bacteria.

    I also found the linked 2004 article from Wired really interesting:

    The Mystery of the Coca Plant That Wouldn't Die

    by Joshua Davis

    Over the past three years, rumors of a new strain of coca have circulated in the Colombian military. The new plant, samples of which are spread out on this table, goes by different names: supercoca, la millonaria. Here in the southern region it's known as Boliviana negra. The most impressive characteristic is not that it produces more leaves - though it does - but that it is resistant to glyphosate. The herbicide, known by its brand name, Roundup, is the key ingredient in the US-financed, billion-dollar aerial coca fumigation campaign that is a cornerstone of America's war on drugs.

    One possible explanation: The farmers of the region may have used selective breeding to develop a hardier strain of coca. If a plant happened to demonstrate herbicide resistance, it would be more widely cultivated, and clippings would be either sold or, in many cases, given away or even stolen by other farmers. Such a peer-to-peer network could, over time, result in a coca crop that can withstand large-scale aerial spraying campaigns.

    It's a long article, but very compelling. The scenario that comes out as likely in the end is a case of natural adaptive introgression:

    Which points back to selective breeding. The implication is that the farmers' decentralized system of disseminating coca cuttings has been amazingly effective - more so than genetic engineering could hope to be. When one plant somewhere in the country demonstrated tolerance to glyphosate, cuttings were made and passed on to dealers and farmers, who could sell them quickly to farmers hoping to withstand the spraying. The best of the next generation was once again used for cuttings and distributed.

    This technique - applied over four years - is now the most likely explanation for the arrival of Boliviana negra. By spraying so much territory, the US significantly increased the odds of generating beneficial mutations. There are numerous species of coca, further increasing the diversity of possible mutations. And in the Amazonian region, nature is particularly adaptive and resilient.

    Could be true, but I couldn't find any later work confirming the existence of glyphosate resistance; just a lot of references to this one Wired article.

    Tags: 
    introgression
    non-primate

  • More on bison and introgression

    Tue, 2007-01-09 09:26 -- John Hawks

    Jim Robbins of the NYT has written a long article about genetic introgression of cattle genes into bison populations. The article is mainly concerned about management, and wildlife managers are trying to minimize the proportion of cattle genes in their conserved herds:

    Over time, cattle genes have spread into many of the remaining herds of American bison. Since the late 1990s, Dr. Derr and his graduate students have traveled to public and private bison herds around the country, taking blood samples. They have concluded that the vast majority of the 300,000 or so bison in the United States are hybrids, though they look like pure bison. Fewer than 10,000 bison are genetically uncontaminated.

    The whole idea of "genetic contamination" implies that there is something bad about this genetic introgression. But we can guess that the cattle genes don't intrinsically reduce fitness, since bison with cattle genes have been greatly increasing in numbers. And these introgressed herds are unlikely to be fixed for any cattle genes, so the original bison alleles still have every chance to compete with the cattle alleles. In other words, the cattle introgression has introduced variation into bison, some of which might be adaptive.

    As you can tell, I'm not very sympathetic to the idea that we should prevent "genomic extinction" by insisting on some kind of genetic purity. It seems to me that we want to retain as much variation in our conserved populations as possible, so that they can adapt to changing climatic conditions in the future. We can't predict which alleles will be adaptive.

    The geneticists in the article worry that cattle genes will make the bison susceptible to cattle-borne diseases like Texas fever. But making a large herd of genetically uniform bison is hardly the way to prevent disease!

    Now, a history of selection for docility on ranches is of more concern:

    "Ranchers might get rid of a cantankerous bull, for example," said Curt Freese, a biologist who directs Great Plains bison restoration for the World Wildlife Fund. "Breeding bison to be docile and meaty are the kinds of things that affect the wildness of the bison."

    But it's unpredictable what behavioral traits will adapt bison to a conserved herd, which after all must be smaller and occupy a lot less space than many of the ancestral bison herds. They may end up more docile anyway, or just the opposite. I tend to think that selection will sort all this out.

    Managers of these herds must also keep a wary eye on hybridized invaders. In Yellowstone, officials found a domestic bison that had wandered into the wild population from a neighboring ranch. And Wind Cave National Park is adjacent to Custer State Park, where the animals are hybridized.

    The new approach may change other aspects of management, as agencies move from managing the species to managing the genetics. Dr. Derr is involved in a study, for instance, of whether the hunting of the bison that leave Yellowstone might be selecting certain behaviors from the population because animals that migrate are targeted.

    This kind of selection is unavoidable in conserved populations, and might even be desirable -- they do, after all, want to stop the bison roaming out of the park. Roaming out of the park is one of the more noticeable bison phenotypes. I'm more worried about all the selection that is happening but doesn't have obvious effects.

    This seems like a good doctoral project for somebody: how do the introgressed bison compare behaviorally with "genetically pure" bison? And the all-important question: how does mean fertility compare between these herds? They've both historically grown very rapidly, but does one maintain higher mean fitness than the other? Are there more animals in the Custer herd that fail to reproduce?

    Anyway, there was no way to quantify the introgression until recent molecular techniques made it possible, and Ted Turner and others were happy to breed large bison herds that contained introgressed cattle genes. The only difference now is that wildlife managers know that some herds are "more pure" than others. But making conservation decisions on "purity" seems less relevant than fitness, which they still don't know much about because it's harder to measure. There is a presumption that the originally bison alleles will be more fit, but today's conserved situations are very different from those faced by ancient bison. And the historic bison -- the ones shot up by Buffalo Bill -- were facing a very novel environment compared with their ancestors.

    The best we can hope for is a capacity for adaptation, which will maximize the chance of survival. In that context "genetic purity" is less important than genetic variability.

    Tags: 
    conservation
    introgression

  • New Year's predictions, 2007 edition

    Tue, 2007-01-02 14:52 -- John Hawks

    It's a hazardous business, making predictions -- all the moreso because New Year's predictions have a deadline. If they don't happen this year, well, that's too bad, because we'll be checking back a year from now to see how well you did.

    Last year, I did pretty well. My 2006 predictions are listed below. I ordered them originally "from most certain to most speculative". As you can see, the first five (i.e., the more "certain" ones) all came true; the last five (i.e., the wild-arsed speculations) didn't. So let's check them out:

    • 10. We will see a name for the Flores pathology. OK, we got several names, and the issue is far from settled, but this was the year that the Homo floresiensis doubters struck with their papers on the remains.
    • 9. There will be two Neandertal genome-related announcements. I undercalled this, since there were three -- the initial announcement in June of the Neandertal Genome project, the announcement and publication in November of the initial sequence results, and the announcement about possible introgression of microcephalin.
    • 8. No Ardipithecus. Sometimes, predictions write themselves.
    • 7. "Population cluster" will become the new "race". This one is debatable, but enough papers on multi-ethnic SNPs have used the term this year, that I think it is emerging as the replacement for the race concept for a certain class of geneticists. I expect it will continue -- "cluster" has such a neutral computer-program-centric connotation, that people like to use it.
    • 6. There will be another paper (yes, besides the one last month) using genetics to estimate the time of the human-chimpanzee divergence. The date will be 5 million to 7 million years ago. Oh, my. There have been bigger messes than the Patterson et al. 2006 paper, but not many. Yes, it was yet another paper with a 5-million to 7-million-year-old divergence, but it had so much more!
    • 5. Evidence of recent selection will be found for several Y chromosome genes. Wishful thinking or prediction for the next year? You decide!
    • 4. Sahelanthropus postcrania will be published. This one didn't happen this year, but I'm carrying it over onto the 2007 list.
    • 3. There will be an ancient DNA announcement from China. Someday it will happen, but not this year or next.
    • 2. StW 573 will be proposed as a new species ancestral to all later hominids. Well, we got the opposite -- with a new younger date, StW 573 was proposed as the ancestor of...nobody! Which was by far the smaller of the redating stories this year.
    • 1. A Hawks weblog post will be cited in a peer-reviewed research paper. We can only hope this happens in the coming year, but carrying it over just seems desperate...
    • BONUS: A new Georgian hominid will be a robust australopithecine. I still think somebody will find an australopithecine outside Africa in the next decade, but it's not to be from Dmanisi -- the hominids are too localized in a single feature.

    So that should give some indication of how to read the list for the next year. I'm listing from more certain to more speculative again, and again I'm excluding most of my own work. The main effect of this is just that I'm not including secrets that I know will be coming out this year. Once again, the predictions are Delphic -- if only I were cleverer, I could make them come out right no matter what!

    • 10. Sahelanthropus postcrania will be published.
    • 9. Two words: Holocene evolution.
    • 8. Despite (or because of) the success of the Neandertal genome project, there will be no genetics of any kind published on early modern skeletal material.
    • 7. The mitochondrial history of human dispersals will become more and more detailed, but no paper will test against other loci.
    • 6. Another (yes, another) paper about the chimpanzee-human divergence will peg it between 5 and 7 million years ago.
    • 5. Three papers with new Ethiopian fossils.
    • 4. Another early Upper Paleolithic specimen will emerge from a museum collection.
    • 3. A big year for Miocene apes, which will look increasingly important in the story of human brain evolution.
    • 2. Maturation rate in early Homo becomes a dead issue, because of the variation in dental and skeletal maturation in living people.
    • 1. The year will end without a single new hominid species having been named.
    • BONUS: A dramatic development in the problem of pre-2.0-million-year-old Homo.

    I ended the year with just a shade fewer than 1 million visits since last January 1. The Neandertal women brought me over 10,000 readers in a single day -- the most ever. I know a few of the big stories from the coming year, but there will be many more that nobody can predict. There's no doubt in my mind that 2007 will be a big year!

    Tags: 
    Flores
    Neandertals
    Ardipithecus
    Koobi Fora
    Dmanisi
    Miocene
    Homo erectus
    Sahelanthropus
    introgression

  • The inevitability of introgression

    Mon, 2006-12-18 17:26 -- John Hawks

    I'd like to draw your attention to my new article on genetic introgression from archaic humans, written with Gregory Cochran. The article is in PaleoAnthropology, and is completely open access.

    I can't say enough good things about this process and the value of having open access research results, which can be downloaded free anywhere on the planet.

    A search for "introgression" here on the weblog will bring up a lot of relevant material, including the introgression and MCPH1 FAQ, a quick note about the importance of introgression in wild species, an opinion about why "introgression" doesn't imply "speciation", and the all-important Neandertal genome FAQ. I've been writing about the subject a lot, because we've been thinking about it a lot.

    If you read nothing more, this is the most important quote (p. 104):

    If the modern human population expanded at a rate of 1 percent per generation, then an introgressive allele with s = 0.01 (i.e., a 1 percent fitness advantage) would have a 95 percent probability of fixation in modern humans, with only 74 archaic-modern matings. For an allele with a 5 percent fitness advantage, the corresponding number of events would be only 24.

    Here, I don't want to repeat all of what I've written already, but I want to jot down some of the reasons why our new paper is worth reading:

    1. The central point of the paper is exceedingly simple. Haldane demostrated in 1927 that the fixation probability of a single copy of a new adaptive allele is 2s. This means that if archaic humans had any alleles that would have been adaptive for modern humans, it would take only a very small amount of interbreeding for modern humans to pick up these alleles, with a near-100 percent likelihood.
    2. One may point out that if this simple genetic observation were accurate, then natural populations ought to display many examples of introgression. In fact, they do. We have laid out a very extensive review of instances of introgression among natural populations. We focused on cases where the introgressive gene had adaptive importance. This included a large number of instances of introgression from wild to domesticated species and vice-versa, which are well-known from breeding experiments. However, there have been a growing number of examples of adaptive introgression between different natural populations as well. The use of more nuclear markers has begun to uncover many, but importantly many species have adaptive introgression of mitochondrial DNA. Those European mice are not unique -- the phenomenon is widespread.
    3. The neatest example we drew upon was the extended phylogenetic history of cattle-bison introgression. It's too long to quote, but it may by itself be worth reading the paper. The geographic and ecological differentiation of cattle may be a strong parallel to the different Pleistocene populations of Homo.
    4. In case you think bovines are too weird to apply to hominids, we also review many domesticated mammals from Eurasia that have very strong east-west biogeographic differentiation with substantial introgression in recent times, in many cases involving two or more wild progenitor species. Ecological change -- including domestication -- appears to be the biggest factor underlying adaptive introgression in animals. One of the most important mechanisms in wild populations is the absorption of endemics by cosmopolitan species through introgressive hybridization. Both mechanisms may have driven modern human origins.
    5. The simple predictions for adaptive genes differ greatly from the predictions for neutral genes. We expect that introgression was centrally important for the evolution of adaptive features of modern humans, both within and outside of Africa. This does not conflict with the observation that the ancestry of a neutral locus is predominantly or even exclusively African. Indeed, our paper suggests that the ecological circumstances surrounding an African population dispersal may have strongly favored the introgression and subsequent redispersal of Eurasian alleles.
    6. One of the big reasons why our paper differs from earlier work is that we consider genetic effects rather than species definitions. There is a long literature on species concepts that -- to varying degrees -- discuss mammalian hybrids. I especially recommend work by Trent Holliday in a 2003 review of species concepts and a forthcoming book chapter, a long series of articles by Clifford Jolly (culminating in a 2001 review article, Darren Curnoe and Alan Thorne in a series of articles (e.g., 2001). Analogy with the systematics of other taxa will always be important in paleoanthropology, because we cannot observe the reproductive behavior of extinct hominids. All these studies and many others agree that some amount of interbreeding between regional populations of archaic humans would have occurred. In this context, the importance of introgression is now in the realm of direct quantification rather than analogy. It makes little difference whether hominids were more like baboons or more like some other model. Humans are the one primate species for which adaptive introgression is now most amply documented.

    We briefly discuss in this paper several loci that demonstrate introgression in humans, but we have reserved a more extensive review for another forthcoming paper.

    There is a lot of action on this front right now, because our knowledge of variation across the genome has become ripe for it. In short, with 25,000 genes to work with, there are unquestionably many that have drawn their adaptive nature in modern humans from some archaic population. It remains to be discovered just how many there are, and what proportion of them come from different archaic populations.

    We think that this is one of the two major forces underlying the emergence of modern humans, and one that underlines the enormous evolutionary potential of our species. As we conclude:

    The notion that a single small population of incipient modern humans had the perfect genetic combination for ultimate success seems quite improbable. Instead, the long coevolution of modern anatomy and behavior in contact with archaic humans, even as those archaic populations appeared to diminish, provided a rich source of adaptations for the expanding modern population. With current genomic techniques, we are beginning to find these archaic genes. We expect that they will prove central to the story of modern human origins.

    References:

    Hawks J, Cochran G. 2006. Dynamics of adaptive introgression from archaic to modern humans. PaleoAnthropology 2006:101-115. Free full text

    Tags: 
    Neandertal DNA
    introgression
    Neandertals

  • Quote of the day

    Mon, 2006-12-18 17:23 -- John Hawks

    G. Ledyard Stebbins, on p. 241 of "The role of hybridization in evolution," Proceedings of the American Philosophical Society 103:231-251, 1959:

    We inevitably reach the conclusion, therefore, that introgressive genotypes not only persist indefinitely, but that also, like polyploids, they can migrate far beyond the areas in which they originated, and can actually survive after the non-introgressed parental species has become extinct.

    (quoted in our own paper, "Dynamics of adaptive introgression from archaic to modern humans," available as free full text):

    Tags: 
    introgression
    humor
    quotes

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Neandertals

For years, I've worked on their bones. Now I'm working on their genes. Read more about the science studying these ancient people.

Denisova

From a finger bone of an ancient human came the record of a completely unexpected population. My lab is working on the science of the Denisova genome.

Acceleration

The advent of agriculture caused natural selection to speed up greatly in humans. We're uncovering some of the ways that populations have rapidly changed during the last 10,000 years.

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Just outside Johannesburg, the Malapa site is producing some of the most exciting finds in human evolution. This site is the headquarters of the Malapa Soft Tissue Project.