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Why would I want my doctor to have studied evolution?

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From Dr. Michael Egnor:

No Nobel prize in medicine has ever been awarded for work in evolutionary biology. In fact, I think it’s safe to say that the only contribution evolution has made to modern medicine is to take it down the horrific road of eugenics, which brought forced sterilization and bodily harm to many thousands of Americans in the early 1900s. That’s a contribution which has brought shame—not advance—to the medical field.

So ‘Why would I want my doctor to have studied evolution?’ I wouldn’t. Evolutionary biology isn’t important to modern medicine. That answer won’t win the ‘Alliance for Science’ prize. It’s just the truth.

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Comments
Jerry: Thanks for the kind remarks. THe civility is in no small measure due to the approach taken by G-A, and we must all be thankful to him for his time and gentlemanly conduct. For the sake of clarity, it may be worth excerpting Wiki briefly on how S-type mutations may protect against malaria:
The best-studied influence of the malaria parasite upon the human genome is the blood disease, sickle-cell disease. In sickle-cell disease, there is a mutation in the HBB gene, which encodes the beta globin subunit of haemoglobin. The normal allele encodes a glutamate at position six of the beta globin protein, while the sickle-cell allele encodes a valine. This change from a hydrophilic to a hydrophobic amino acid encourages binding between haemoglobin molecules, with polymerization of haemoglobin deforming red blood cells into a sickle shape. Individuals homozygous for the mutation have full sickle-cell disease and rarely live beyond adolescence. However, this allele has sustained gene frequencies in populations where malaria is endemic of around 10%. This is because individuals heterozygous for the mutated allele, known as sickle-cell trait, have a low level of anaemia but also have a greatly reduced chance of malaria infection. The existence of four haplotypes of sickle-type hemoglobin suggests that this mutation has emerged independently at least four times in malaria-endemic areas, further demonstrating its evolutionary advantage in such affected regions. There are also other mutations of the HBB gene that produce haemoglobin molecules capable of conferring similar resistance to malaria infection. These mutations produce haemoglobin types HbE and HbC which are common in Southeast Asia and Western Africa, respectively.
Proteins fold based in part on water-soluble and water-insoluble amino acid elements. In this case the point substitution of hydrophilic for hydrophobic encourages an undesirable cross-linking. The resulting effect is that here is in the SA form a mild and in the SS a serious form o the sickle cell condition. One result is that evidenty malarial pathogens have problems penetrating an indhabiting such cells. But their primary functionality is also damaged. People with SS, in primitive situations, die young. SA types are prone to various health problems and vulnerabilities. They also tend to give birth to children who suffer the SS condition. [SA x SA --> 25% SS, 50% SA, 25% AA. Compensating for the resulting "weak" health of offspring may partly explain the observation in AL that SA mothers tend to have more children.] The complexities come in as we see the rest of 700 variants on haemoglobin, and on the anomalies relativge to the Haldane NDT-style model, that S seems more persitent than the simple model predicts. I have just put up two more variants that show just how diverse the situation is with malaria. For, it seems the "best" example of a protective mutation that "wins" the genetic horserace, protects against the milder form of the disease, and a variety of Haemoglobin that protects against severe malaria, has not won the race, though it does not seem to have immediately noteworthy major damaging effects. [NB: the more virulent form seems to have multiple pathways to invade blood cells. That makes it far more complicated to deal with than Pv, the more mild type protected against by omitting Duffy's antigen.] Thus, med students need to hear a quite nuanced story. And, we the public should not be given a simplistic picture on malaria and sicle cell disease. All the best GEM of TKIkairosfocus
March 25, 2007
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I have watched this debate as I am sure many others have and the interesting thing besides the general level of civility is how little there is to support the Darwin paradigm. Though I do not know much about the details of genetics it is possible to follow the gist of the arguments and make some conclusions. Genetics is obviously an extremely important discipline when focused on medicine and diseases and how they are passed on generation to generation. We should never underestimate this. But when genetics is applied to evolution on a grander scale than just explaining the changes of allele frequencies over time it comes up empty. Natural selection is definitely a mechanism of genetics but it is an extremely limited one. Otherwise we would be looking at an endless laundry list of its effects. Instead we are focused on a few case of degeneration that lead to a posiitive benefit.jerry
March 24, 2007
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Finally for now: I also ran across HLA-B53. This, from NIH, seems worthy of following up:
Another version of the HLA-B gene, HLA-B53, has been shown to help protect against severe malaria. HLA-B53 is most common in West African populations, where malaria is a frequent cause of death in children. Researchers suggest that this version of the HLA-B gene may help the immune system respond more effectively to the parasite that causes malaria.
In looking for stuff on prevalence, I came across this, in a Sept 2000 NEJM review paper:
In the Gambia, infection with Plasmodium falciparum, which causes malaria, is extremely common, although the mortality rate among children with malarial anemia or cerebral malaria is low. Both complications are believed to be the consequence of a failure to clear the parasites from the blood, leading to increased hemolysis and blockage of cerebral blood vessels by parasitized erythrocytes. HLA typing of the relevant population revealed the presence of the HLA-B*53 allele at a frequency of approximately 25 percent among healthy persons or children with mild malaria (the allele is rare in non-African populations). By contrast, the frequency of HLA-B*53 among patients with severe malaria was approximately 15 percent. The comparison suggests that possession of the HLA-B*53 allele reduces the risk of death from severe malaria by approximately 40 percent. Presumably, the HLA-B53 molecules bind very efficiently certain peptides produced by processing the malarial circumsporozoite protein and present them to CD8+ T cells, whose progeny attack the liver-stage parasites. Such cytotoxic T cells have indeed been found in patients with malaria, and circumsporozoite peptides have been eluted from the HLA-B*53 molecules of these patients. 40 Protection against severe malarial anemia is also afforded by possession of the class II HLA-DRB1*1302/DQB1*0501 haplotype. In other sub-Saharan populations, different class I and class II alleles are involved in the resistance to severe malaria.
This gives us at least some prelim numbers on general prevalence [for which healthy persons and/or mild malaria is probably a reasonable proxy] and on differential presence among pops with mild/severe malaria. While this variation is obviously relatively common in African pops and rarish elsewhere, why did it not outright win the genetic race in Gambia etc, instead of latching [if it has latched . . . YECs note] at the sort of 20% level level we are seeing? This 1994 Colloquium paper is also worth a look, to see the conventional account in summary form, including a brief ref to HLA-B53 and other interesting cases. This story has much more to it than meets the eye . . . GEM of TKIkairosfocus
March 24, 2007
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PPPS: The case of the Duffy antigen is an interesting parallel. Of this Wiki notes:
Plasmodium vivax malaria uses the Duffy antigen to enter blood cells. However, it is possible to express no Duffy antigen on red blood cells (Fy-/Fy-). This genotype confers complete resistance to P. vivax infection. The genotype has not been found in Chinese populations [nb China is of course in the Malaria belt], has rarely been found in white populations, but is found in 68% of black people. This is thought to be due to very high exposure to P. vivax in Africa in the past.
I think that gives a bit of further context; especially on what winning a genetic horse race can look like. (Including of course mutation through evident loss of information.) It is worth noting that the selection forces seem to have worked that extensively in the face of a LESS serious form of the disease, one that would have had far less damaging impact on reproductive potential:
The parasite Plasmodium vivax is the most frequent and widely distributed cause of benign, but recurring (tertian), malaria. It is one of four species of parasite that commonly cause malaria infection in humans. It is less virulent than Plasmodium falciparum, the deadliest of the four, and seldom fatal.
Or, is it that the founder african population[s] just happened to be predominantly of the relevant genetic variant? [In short, we again see the problems of "scientifically" reconstructing the past . . . we have to look at relative plausibility of competing explanations, not "proofs."] GEM of TKIkairosfocus
March 24, 2007
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Oh yes: I should comment a bit on 0.2^2 ~ 0.04, which is of course still a small minority, though not as low as with other similar genetic diseases. (Recall, we are looking at environments where malarial mosquitoes were/are abundant and hungry, and where across time, little could be done to prevent being bitten.) Even in such environments, which were presumably in several cases also relatively reproductively isolated for many generations, we did not see S dominating the population. That is why I spoke of other horses winning the race, and note PaV's remark in 80:
given that there are so many different types of ‘heterozygotes’ for hemoglobin—sickle cell, thalassemia, dust antigen, HLA, etc., etc.—the more sensible interpretation is not that ALL of these confer any kind of ‘heterozygote advantage’, but simply that when it comes to hemoglobin its complex structure permits a number of heterozygotes appearing without lethality. IOW, the recessive homozygotes are not sufficiently lethal as to eliminate them from a population entirely, so there remains a kind of ‘residual’ allele frequency. That’s my hunch.
So, yes there may be some empirically demonstrable protective effect against malaria in S-distorted haemoglobin -- in this case balanced off by a disease that is serious in SS form and what we may call mildly present with damaging consequences and potential consequences in SA form – but there are other possible horses in the race. In particular, people with more “normal” haemoglobin – forms that appear to be vulnerable to malaria -- actually do predominate even in the teeth of what has been called the most stringent selection pressure on the human genome in “recent” times. One that wiki characterises as:
one of the most common infectious diseases and an enormous public-health problem . . . . has infected humans for over 50,000 years, and may have been a human pathogen for the entire history of our species.[1] Indeed, close relatives of the human malaria parasites remain common in chimpanzees, our closest relatives.[2] References to the unique periodic fevers of malaria are found throughout recorded history . . . . causes about 350–500 million infections in humans and approximately one to three million deaths annually[13] . . . The vast majority of cases occur in children under the age of 5 years;[14] pregnant women are also especially vulnerable . . . Precise statistics are unknown because many cases occur in rural areas where people do not have access to hospitals or the means to afford health care. Consequently, the majority of cases are undocumented.[13] . . . . Malaria is presently endemic in a broad band around the equator, in areas of South America, South and Southeast Asia, parts of the Middle East and Oceania, and much of Africa; however, it is in sub-Saharan Africa where 85– 90% of malaria fatalities occur . . . . Malaria is not just a disease commonly associated with poverty, but is also a cause of poverty and a major hindrance to economic development . . . economic impact includes costs of health care, working days lost due to sickness, days lost in education, decreased productivity due to brain damage from cerebral malaria, and loss of investment and tourism.[14] In some countries with a heavy malaria burden, the disease may account for as much as 40% of public health expenditure, 30-50% of inpatient admissions, and up to 50% of outpatient visits.[25] . . . . Symptoms of malaria include fever, shivering, arthralgia (joint pain), vomiting, anemia caused by hemolysis, hemoglobinuria, and convulsions. . . . For reasons that are poorly understood, but which may be related to high intracranial pressure, children with malaria frequently exhibit abnormal posturing, a sign indicating severe brain damage.[27] Malaria has been found to cause cognitive impairments, especially in children. It causes widespread anemia during a period of rapid brain development and also direct brain damage from cerebral malaria to which children are more vulnerable.[28] . . . . Consequences of severe malaria include coma and death if untreated—young children and pregnant women are especially vulnerable . . . . Severe malaria can progress extremely rapidly and cause death within hours or days.[29] In the most severe cases of the disease fatality rates can exceed 20%, even with intensive care and treatment.[30] In endemic areas, treatment is often less satisfactory and the overall fatality rate for all cases of malaria can be as high as one in ten.[31] Over the longer term, developmental impairments have been documented in children who have suffered episodes of severe malaria.[32]
We can easily see why such an awful disease would put serious genetic pressure on the affected population. That means that there would be a huge, fast-building genetic reward for something that confers resistance, which should therefore rapidly dominate the population. But, S simply has failed to do so. Other horses have won the race, despite their handicaps. Why? As we try to look at that why, the story as seen above, gets complicated real fast – starting with data patterns. So, it is fair comment to note that there seems to be a lot more to the story than meets the casual eye. And, that is what med students should know. GEM of TKIkairosfocus
March 24, 2007
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Hi All Indeed, this thread has now come to a mutually respectful consensus on key points. GP, in 133, has summed up pretty well. Feyerabend is in fact one of my personal intellectual mini-heroes [or, should I say antiheroes . . .], and he is right to raise the issue of microevolution as the claimed building block of macroevolution, but one dogged by information-generation challenges as discussed previously and mentioned above. PaV correctly guesses in 134, that I find myself troubled by the equivocation that haunts terminology in this field. (One of the very first things I learned in 4th form Physics was the definition of a definition: a precise, accurately descriptive statement. I am forever and gratefully indebted to my first full Physics teacher, Mr Anthony Craven, for his focus on clarity and exactness of expression. I hope that in my onward studies and career, I have lived up to his hopes and dicta.) I think, DV, I will soon feature this thread in my own blog as an example of how a critically aware discussion of evolutionary issues can be undertaken without rancour and what happens as a result. For that, G-A must receive kudos. I will note on a few points as per G-A's last response justabove: 1] Local Jamaican data: Yes, they used such data. What makes me think they twiddled to get a match to the 1970s cohort is the remark :We found that although model predictions were broadly consistent with observed values in the 1973-1981 cohort, the predicted change in allele frequency between the two cohorts was larger than the observed, nonsignificant, reduction. Had the calibration data been truly independent of the 1970s cohort, I am confident they would have said, “predicted,” not “broadly consistent.” Nothing is wrong with that semi-empirical approach, once one recognises what one is doing: the 1935 Weizacker liquid drop semi-empirical nuclear mass model is famous in Physics. There are certain dynamical considerations and assumed initial conditions, and then we tune the parameters to get a match to a known empirical point. Then, we project and test to see if the model has predictive not just generally explanatory power. Note the distinction I am making here between explanation in general terms and actual predictive power [or retrodicting power]. (BTW, such an approach is how climate models are developed and tuned, then run – and hence in part the controversies and limitations, as SD and GD etc love to highlight on their favourite off-topic. Similarly, here in Montserrat, our public is this week debating the pros and cons of a recent super-computer simulation on a possible lateral blast explosion of the growing lava dome, that could engulf Salem, the nearest currently occupied village. The model is basically an extension of the blast that happened Dec 26, 1997 that wiped out several evacuated villages in the South. But, evacuations are expensive and disruptive . . .) When they moved on from explanation to prediction, things fell apart, preliminarily showing that the model is too simplistic. And that is what is at the crux of our own discussion. Going further, we are seeing a situation where damaging changes to the genome are stabilising in the population, in this case at a rate of several percent – instead of being swept out as one or more of the remaining 600+ horses wins the race. So, there are other dynamics that are credibly at work. YECs may wish to question whether the real world timeline has had time to get to an outright win instead of a split difference. Those who view NS as perhaps less efficient than sometimes presented [PaV], will challenge the idea that the best horse wins outright. Perhaps what is happening is that the genome is deteriorating under impact of noise and those variations that are not utterly lethal or destructive to reproductive capacity are preserved one way or another, more or less leading to a more or less stabilised situation? [Here, “stability” can include oscillations via limit cycles etc.] But the point is that med students need to know that data come first, that theories and models have limitations, and that we need to be open to being wrong, and so make the effort to put forth creative ideas that may be wrong, but are fruitful along the way . . . GEM of TKI PS cf here on hyps, models and theories.kairosfocus
March 24, 2007
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"Now consider that in some regions of Africa, approximately q^2 or (.20)*(.20) people are expected to be born with the disease. That’s 1 out of every 25 people" --me I am referring to sickle-cell anemia here as "the disease." I should have been more clear.great_ape
March 23, 2007
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I agree the thread has run its course. A few final points, though. 1. The sickle cell allele in malaria-endemic regions in Africa ranges from 5-20% in frequency depending on the region (around 8% for African-Americans). This data is obtained from sickle-cell medical info around the internet; I unfortunately can't find a good article from home, but I trust this figure is in the ballpark. For an allele that's as harmful as S is in its homozgygous state (and sometimes in its heterozygous as kairosfocus points out) this is highly unexpected and demands explanation. This is not something that's just stochastically lingering by chance, as some have suggested. 2. kairosfocus, indeed they seem to have used local jamaican data to calibrate their model. Yet there is nothing whatsoever I can find that suggests they calibrated it so as to *fit* the first cohort. I'm not clear how or even why they would choose to orchestrate the fit you suggest. That would completely undermine their experimental design. And such a fit (if it was their intention) only makes it more difficult to explain their data, as they now have to explain why there was a *change* in the allele dynamics after the first cohort was reached. Generally, this "fitting" idea you suggest is precisely what people try to avoid by using empirically-derived parameters. The only manipulation they do is *subsequent* to the initial model test, when they try to discern what *would* have needed to be true of the fitness parameter to make the model fit the last period from 1973-2003. That is my understanding. 3. gpuccio, kairosfocus, let us continue the microevolution and associated nomenclature discussion on a future thread. 4. "What I would like to see is the causal explanation of why SA women seem have more kids in AL." --kairosfocus I too would be very interested to know. 5. "How do we move beyond such a relativistic assessment of beneficial/deleterious?" --PaV A fair question. This is achieved in evolutionary biology by generally considering a trait's "benefit" or "relative fitness" as a function of relative reproductive success of the trait's carriers. That is what is what is either explicitly or implicitly being done in the studies we are discussing here. Finally... 7. "in fact, another horse HAS won the race – S is evidently a distinct minority even among notoriously malaria prone populations. " --kairosfocus Yes, but as I pointed out above, 5-20% frequency of the S-allele is *not* the miniscule minor frequency you'd expect from a recessive genetic disorder of that severity. THAT is what has raised a flag all these years that something else must be going on. And hence the malaria theory. Mendelian diseases that survive in populations, depending on their severity, persist at much lower frequencies. Consider cystic fibrosis and similar mendelian diseases and how many people you know have them. Now consider that in some regions of Africa, approximately q^2 or (.20)*(.20) people are expected to be born with the disease. That's 1 out of every 25 people. But as you all have noted, we can at least agree that the picture is not quite as simple as it is often presented. Yet, to my mind, the take-home message from the malaria/sickle-cell stands, in essence, as an important illustration of the concept of balancing selection as well as helping us understand why a deleterious trait might be found at *unexpectedly high* frequencies. I too have appreciated the unfortunately all-to-uncommon civil discussion, and I've learned a few things and brushed up on a few others. (By the way, gpuccio, thanks for the correction; I should definitely *not* have included discussion of complex diseases (alzheimers, etc.) when we were specifically discussing simple mendelian diseases. A particularly inexcusable oversight on my part. I rather hope this is attributable to my haste and not the premature manifestations of a genetically complex neurodegenerative disease.)great_ape
March 23, 2007
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great_ape: But for you I detect “evolve” must correspond to something akin to “create” or “build.” That is an association you have formed, for understandable reasons, but not one which is consistent with how the term “microevolution” is used amongst biologists. To “evolve” simply indicates “change”. Sometimes change can be “constructive” in nature, sometimes it’s simply change." gpuccio: still maintain that such a minimal form of possible genetic change should be called “micro-variation”, and not “micro-evolution”, but who am I to challenge the semantic whims of the scientific community? Alas, I stay convinced that semantics is important, and that such an “unnatural” extension of the meaning of “evolution” in common scientific language has definite ideological connotations. Here's something posted at physorg.com today about 'Ancestral Eve and tooth decay bacteria': "As humans migrated around the world and evolved into the different races and ethnicities we know today," Caufield said, "this oral bacterium evolved with them in a simultaneous process called coevolution." I, in agreement with gpuccio,(and kairosfocus I would think) am troubled by the kind of equivocation that seems to be part and parcel, i.e., typical, of Darwinism. As the quote I provide illustrates, the word "evolve" is being used equivocally. IOW, the only way that 'bacteria' can co-evolve is if the host 'evolves' as well. Humankind is that host. So now, here comes---per force---the statement that humanity "evolved" into different "races" and ethnicities. This is the kind of thing that Darwinists say all the time, unreflectively, and it only causes science to become muddled. Oftentimes when I am reading a scientific article I actually have to *translate* what the scientists are saying since the language they use and the actual results they're attempting to describe don't match up. It is my sense that in the current debate, the Darwinian side, rather than attempting to avoid equivocations, actually is adding to the numerous equivocations that are already out there. To me, this only makes a daunting task all the harder. As an example of an equivocation that's just out there, and seems hopeless to be resolved, is in regard to the "beneficial effects" of an otherwise deleterious mutation. When great_ape responded thusly.... Not a beneficial trait in *any* way? When combined with a normal allele it appears to confer appreciable malaria resistance. That’s a benefit, any way you slice it. It’s not an *elegant* way to confer resistance, but it’s a *way*. Hence a benefit in the appropriate context (genetic and environmental). Context is key. ... my thoughts were: "Is blindness beneficial? Not really. But in the context of an electrical blackout, yes, indeed, it does have its advantages." How do we move beyond such a relativistic assessment of beneficial/deleterious? In this regard, I appreciate gpuccio's recurring question of how much 'function' is being added. This type of question might provide some adequately objective way of gauging 'benefit' versus 'harm', thus allowing us to at least avoid this equivocal use of "beneficial." Finally, I think this thread has gone on about as long as it can so while still being constructive. (Although I'll keep looking back to see if others are choosing to continue) I, too, feel that I've learned a lot. And great_ape's challenges have forced me to more rigorously think through certain ideas. I'm thankful for that. I'm also thankful for the kind of summaries that both gpuccio and kairosfocus have provided.PaV
March 23, 2007
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kairosfocus: "In short, we are moving to a consensus" That's also my feeling. I am very happy that the discussion here has proved very constructive, even with everybody keeping his fundamental views. That's the merit of all. Thank you again, kairosfocus. for adding your usual clarity and wider approach to the debate. You have also literally stolen words from my mouth (in the sense that I was going to say exactly some of the things you highlighted). Great ape, I am very happy with your final considerations, with which I can very well agree, maintaining the slight differences on some important points which should by now be clear. I agree that the discussion here has been very long. Just have patience, and let me add a couple of innocent thoughts, which could be useful fot future discussions (which I really hope we will have together): Consensus 1: Statistics is important, but we must know how to use it. But method is important too, and we must know how to use it. Statistical and methodological analysis are two different, complementary things. Great ape has stressed statistics, PaV has stressed method. Respecting their different emphasis on the specific details, I think that both are sincerely and correctly motivated in doing that. That said, I want to thank kairosfocus for adding the "prevailing paradigm/scientific revolution" perspective, which is very dear to my heart. So let's remember that, while scientific method is certanly important, some anarchistic guys like me can be sympathetic with Feyerabend's views agains it, at least to some degree. Consensus 2: S hemoglobin and malaria. I think we all have learned interesting things, and the subject is obviously open to research (you have certainly noticed that the papers about the variations in malaria free populations are all very recent!). So I am happy that PaV's "provocation" opened the discussion on this specific point. Kairosfocus has already done a good job remembering the negative aspects of the S hemoglobin even in heterozygous form. Just a note to great ape: mendelian disease is a term reserved to single gene diseases, whose heredity follows the mendelian paradigm. In that sense, S cell disease is a recessive (indeed, partially recessive) mendelian disease, exactly like all other recessive diseases, such as beta thalassemia, cystic fibrosis, and many others. The other diseases you mention are multifactorial, poligenic diseases, and they do not follow mendelian rules of heredity. In my opinion, the problem remains of how so many mendelian "single gene" diseases, both recessive and dominant, have persisted in some form of equilibrium in absence of apparent selective pressure, without disappearing or being fixed by genetic drift, or similar "mechanisms". Consensus 3: So, forgetting the details of the S hemoglobin-malaria scenario, what do we do with the concept of "microevolution"? I have much appreciated the following comments by great ape: "But for you I detect “evolve” must correspond to something akin to “create” or “build.” That is an association you have formed, for understandable reasons, but not one which is consistent with how the term “microevolution” is used amongst biologists. To “evolve” simply indicates “change”. Sometimes change can be “constructive” in nature, sometimes it’s simply change. That is why neutral evolution of alleles is still “molecular evolution” even though nothing is selected for. Thus microevolution, in my understanding, is the change of a trait in a population, typically, but not necessarily, under the influence of natural selection. It need not be so grand as to “build” anything. It may simply tweak or help in some way." I think here we can really agree. If “microevolution” is defined in such a minimal way, that is as a molecular change where nothing is built or, in the case of neutral evolution, nothing is selected, I have no problem with it. It is a model which is perfectly possible, but still it remains only a model, unless convincing empirical evidence can be found. So, it should be evaluated in each single context, to judge its true relevance. I still maintain that such a minimal form of possible genetic change should be called “micro-variation”, and not “micro-evolution”, but who am I to challenge the semantic whims of the scientific community? Alas, I stay convinced that semantics is important, and that such an “unnatural” extension of the meaning of “evolution” in common scientific language has definite ideological connotations. But, apart from that, the problem is that “microevolution” is not only supposed to mean the minimal form of variation where, as you say, nothing is built and/or nothing is selected. Microevolution is usually believed to be able to build and/or select. It is usually believed to be the “building-block” of macroevolution. In other words, if “microevolution” did not build anything (as I believe to be the truth), where could macroevolution come from? In the general model, macroevolution is supposed to arise from repeated events of microevolution. But if you build nothing, you cannot sum up a pile of nothings to obtain something (and something big indeed!). So, even not discussing here the necessity for macroevolution to be “deconstructable” as a sum of simple microevolutionary events, each of them selectable, I think that at least we should try to identify and verify (or falsify) a few “microevolutionary” events which really build something. In other words, find a few examples of single documented mutations which have “built” something in the sense of a new function, and not simply destroyed a pre-existing function conferring indirect advantages versus environmental aggressors which were specifically targeted at that function. But, as you have noticed, this thread has become very long. If you want, we can start again the discussion in some future occasion.gpuccio
March 23, 2007
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Continuing . . . 6] GA 125: the protection from SA is more “definitive” than the malaria natural selection hypothesis for *why* S-allele persists in the population at high frequency. But consider the fact that this only seems to be the case in malaria-endemic regions. The second half is on the Jamaica evidence [and that of the other study mentioned, possibly?] under current empirical challenge. S is apparently persisting beyond what credibly acceptable NDT models project. So much so, a clinical intervention is being recommended. So, there is at least preliminary evidence that the story is messier than we “expected” based on NDT models. 7] 127, to GP: for you I detect “evolve” must correspond to something akin to “create” or “build.” That is an association you have formed, for understandable reasons, but not one which is consistent with how the term “microevolution” is used amongst biologists. To “evolve” simply indicates “change” . . . . I’d be happy to discuss microevolution, information, etc. futher, but this particular thread is getting a bit unwieldy. Perhaps an opportunity will arise elsewhere. We now come to the many variations in meaning of the term “evolution.” I note that on a major interpretation of NDT, micro-evolutionary population shifts are held to cumulate to body-plan level systemic innovations sufficient to account for biodiversity in current and fossil biotas. Thus, it is material to observe that creativity of this chance + necessity driven mechanism is not an immaterial factor. In this context, the shift to the concept that evolution is not necessarily creative or progressive is technically true but IMHCO apt to become little more than a subterfuge under pressure of challenge. I note that in particular, the tendency to brush aside the implications of the challenge of getting to information from lucky noise in the face o f the issue of complex bio-functional information required for innovations, to me marks a defensive move of a paradigm in trouble. 8] 128: I should perhaps instead have said that [I believe] the forces (balancing selection) explaining the S-allele genotype and frequencies are of a similar *nature* as those involved in the process of microevolution Consensus approaches . . . 9] When combined with a normal allele it [S] appears to confer appreciable malaria resistance. That’s a benefit, any way you slice it. It’s not an *elegant* way to confer resistance, but it’s a *way*. Hence a benefit in the appropriate context (genetic and environmental) Of course, the 700 [and more] horses issue appears, and the observed and commonplace fact that the SA form is associated with significant and relatively frequent pathologies also, are material. What I would like to see is the causal explanation of why SA women seem have more kids in AL. 10] PaV, 129: in the *largest* sample (by far!), the numbers were almost identical. That should be a red flag . . . . if they had found a small decrease in allele frequency and I suggested that was “noise”, tell me, honestly, what would your reaction have been? This is a significant, empirically anchored point. It needs to be followed up, especially as there seems to be at least one other similar case out there. And, acknowledgement that the re are significant numbers of strange, i.e. unexpected, empirical findings relative to NDT-driven expectations. In short, shouldn't we be rethinking, given that Malaria is rated as perhapsthe single highest evolutionary pressure on the human pop in recent times? 11] let’s add this: what the S-allele seems to do is make malaria less severe (and one can suppose less lethal). If this is true, are there some S-allele carriers who respond so mildly to malaria that they are not reported; i.e., they end up not going to a clinic, not receiving medical care or treatments, which would cause the number of infected S-allele carriers to be undereported. Add that possiblity to the data for Nigeria, and it’s very questionable, then, what, exactly, were looking at. This is a very good question/issue indeed, and well worth following up. Sarly, there i s a factor not much in the discussion – all of this costs a lot of money,a nd the funding goes tot he predominant paradigm as a rule. So, we must be aware of paradigm-bias in what becomes accepted scientific knowledge in any given era. GEM of TKIkairosfocus
March 23, 2007
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Continuing . . . 3] GA, 124: It’s not clear to me from their methods section if they use local data or other studies for calibration. (Presumably if they completely used local empirical data, their model should have more accurately predicted the *recent* allele decline, which is the opposite of what happened) From the Abstract, as cited by me in the point that got through, no 113:
. . . local empirical data were used to estimate the parameters of deterministic models of allele frequency decline. We found that although model predictions were broadly consistent with observed values in the 1973-1981 cohort, the predicted change in allele frequency between the two cohorts was larger than the observed, nonsignificant, reduction.
Seems to me they DID use local empirical data to estimate the parameters of the NS-driven model that would drive the decline. But, on observing the actual data, they found the outcome flat within statistical significance. 4] when I say the model “fit” for the first 3/4 of the time period, I mean that, using those parameters, the 1973-1983 cohort allele frequencies were within the range expected if they had been declining according to the model’s dynamic. Entirely consistent with my remark that it seems they more or less CALIBRATED the model to fit the data as at 1970's or so, i.e. by deriving an estimated original rate with the current W African regions as a proxy for the source circa 250 y a. Then they adjusted semi-empirically as physicists would say. But then with this “deterministic” model, the onward projection failed. THAT is what they are noting. And, let us observe from above that we know that from other studies, shifts in S between adult and child generations are detectable. You yourself cited this above. 5] horse race analogy . . . it really ultimately depends on the details of the other horses . . . It also may be that they weren’t available (i.e. present) in the appropriate populations In short, the picture is more complex than is usually presented, and there is now a question on the efficacy of mutations to create new biofunctional molecules in populations under environmental stress. [Recall, Wiki has noted that this may be the most significant genetic pressure on the human genome in recent times . . .] 5] non-lethal variants can linger in the population as PaV suggested, but *deleterious* variants generally only linger at very low frequencies. (where homozygotes are very rarely seen outside of inbreeding) Here, we have populations where a known significantly deleterious allele (S) is at a relatively high frequency. So it’s clear something else is going on; the question is what. For me the malaria resistance is evidently part of the story. I am now, however, somewhat more open to the idea that there’s another element in the equation. In short, we are moving to a consensus, that he simple story is a bit too simple. So, while med students indeed should be exposed to NDT mechanisms, they should also be exposed to the issues and complexities of the real world – including the gaps and conundrums faced by NDT. (Maybe, too, that is part of why the recent surveys show that doctors are strongly inclined not to take NDT at face value – direct awareness of the messiness of the real world in materially important contexts.) Pausing . . .kairosfocus
March 23, 2007
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Hi All Let me first join Sal in expressing appreciation for the manner in which GA has participated in this and previous threads. In fact, if memory serves, he is by far and away the most civil NDT and/or evo mat advocate I have encountered online over the past two years or so. Now, on points worth a note – duly noting on the “still in filter” comment the way: 1] GA, 121: the presence of the S-allele in *two* separate genotypes SA and SS, one of which is beneficial and one of which is detrimental I think based on already cited remarks by clinicians, and my own observations in Jamaica as I actually met people with SC problems, the highlighted first half of that claim is not so. SCT is associated with symptoms and vulnerabilities that are anything but beneficial. It may confer some protection from malaria, but on the cited evidence, so do a lot of other variants on the protein, so the logical question is why hasn't another horse “won” the race. In fact, another horse HAS won the race – S is evidently a distinct minority even among notoriously malaria prone populations. [So the issue is really why deleterious mutations endure in the population, i.e the problem is within the general issue of genetic diseases, in itself a challenge to the evolutionary dynamics by which innovations are supposed to “take over” populations.] 2] Statistics is a pillar of scientific discourse. (And yes, I know that the framework and assumptions are important) . . . Seeking to undermine every premise offered is not healthy. In fact, the issue is deeper than that. Scientific explanations are per epistemological constraints on empirical knowledge through generally inductive reasoning, inherently provisional, and requires a judgement of trust. But as the paradigms and scientific revolutions concept shows, there is often an issue of worldviews involved too, and also agendas. Science is no freer from such factors than the people involved. In that context, statistics is not better than the assumptions, models and quality of data involved. Sadly, in many cases, cost to collect key data is also a major constraint. In this case though we must note that the data come from two “large” screening studies [and I note the AL study that did sample mothers . . .], in a context where there are credibly well over 10E4 live births per year. It is credible that the samples are an appreciable fraction of that total. The result, on two empirical data points a generation apart [thus capturing two generations], was that within statistical nullity, there is no down trend. There is apparently at least one other study out there that gives a similar result. Another study now brought forth seems to show higher fecundity among AS women. As is not as harmless as has been made out. We also credibly know that there are up to 700 genetic horses in the race. [Cf from suppressed post: here] So the simple Haldane story is probably simplistic. PaV's summary is that evidently things that are not sufficiently lethal to be weeded out will remain in the population. That is almost a truism, and the further point that there is no consistent level of S in similar malaria-prone regions is also significant. Indeed, your remarks above on competing forces and stabilisation in the population are IMHO coming around to that. Pausing . . .kairosfocus
March 23, 2007
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great_ape: "I didn’t mean to suggest he is altogether illiterate. I do have considerable doubts about his familiarity with how science and scientific discourse is generally conducted." Yes, well, you see, the problem is is that "science and scientific discourse" have given us Darwinism as a "fact". Sorry, Darwinism is not science, it's more ideology. great_ape:"Statistics is a pillar of scientific discourse. (And yes, I know that the framework and assumptions are important). There are some basic criteria, which, once we abandon them, we might as well just be stating how we “feel” about the various concepts." Statistics has its place in science, no doubt. But it has its limits. Yes, "junk in--junk out". Yes, an aphorism. You seem to just say: "Give me the numbers. I'll do my magic (plug it into Excel), voila, the answer." Is that science? Now, as to the the data on malarial infection, I've already pointed out that in the *largest* sample (by far!), the numbers were almost identical. That should be a red flag. Then, let's add this: what the S-allele seems to do is make malaria less severe (and one can suppose less lethal). If this is true, are there some S-allele carriers who respond so mildly to malaria that they are not reported; i.e., they end up not going to a clinic, not receiving medical care or treatments, which would cause the number of infected S-allele carriers to be undereported. Add that possiblity to the data for Nigeria, and it's very questionable, then, what, exactly, were looking at. You seem to just take the data at face value. Let me say that looking at the data, doing simple calculations in my head, yes, it's quite obvious what Excel will show. I concede that the data--as given--would, if number-crunched, show a selective advantage for the S-allele. So what. I don't need statistics to tell me that. But that's not the important question here. The important question here is: how reliable is this data? Stated another way: statistics is blind: it doesn't care what numbers it's crunching. Hence, it is absolutely essential that good data be used, that it be screened. From a post by HodorH, here's an example of what I mean: "These data have proved of limited value in defining an empirical relationship between intensity of transmission and death from malaria for a number of reasons, including the insensitivity of indirect techniques for ascertaining cause of death1617; the problems in defining host-parasite exposure through the entomological inoculation rate; and confounding factors such as the presence or absence of effective clinical management for malaria between the sites and over time. The latter cannot be underestimated: at Keneba in The Gambia18 and Mlomp in Senegal19, childhood mortality was reduced to remarkably low levels through the provision of well funded, well staffed and comprehen-sive essential clinical services." This is an example of serious scientific effort. You blindly accept numbers and use statistical methods and say: "This is how science is done." I say, let's look at this data, it looks suspcious, and your response is: "I have considerable doubts about your familiarity with how science and scientific discourse is generally conducted." great-ape: "It’s another thing to be outnumbered and have to illustrate, on top of everything else, that Africans from malaria-endemic regions have a higher rate of sickle-cell anemia." Funny, I don't really remember that being discussed that much. The discussion was rather over whether the S-allele protected Africans from infection or not. It was also about a study that showed no appreciable change in S-allele frequency from one generation to another in a malaria free area. You said this was probably due to "noise". And if they had found a small decrease in allele frequency and I suggested that was "noise", tell me, honestly, what would your reaction have been?PaV
March 22, 2007
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"Well, I will only comment that, according to those definitions, and especially yours, the S trait model is not an example of microevolution. The reasons..." Fair enough. I should perhaps instead have said that [I believe] the forces (balancing selection) explaining the S-allele genotype and frequencies are of a similar *nature* as those involved in the process of microevolution. As I have already said, S hemoglobin can in no way be considered a beneficial trait." --gpuccio Not a beneficial trait in *any* way? When combined with a normal allele it appears to confer appreciable malaria resistance. That's a benefit, any way you slice it. It's not an *elegant* way to confer resistance, but it's a *way*. Hence a benefit in the appropriate context (genetic and environmental). Context is key.great_ape
March 22, 2007
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"Semantic is very important for me, because bas semantic is often a screen for bad thinking, and for hidden lies, like natural selections which don’t “select” anything, or micorevolutions which don’t “evolve” anything." --gpuccio I understand. But for you I detect "evolve" must correspond to something akin to "create" or "build." That is an association you have formed, for understandable reasons, but not one which is consistent with how the term "microevolution" is used amongst biologists. To "evolve" simply indicates "change". Sometimes change can be "constructive" in nature, sometimes it's simply change. That is why neutral evolution of alleles is still "molecular evolution" even though nothing is selected for. Thus microevolution, in my understanding, is the change of a trait in a population, typically, but not necessarily, under the influence of natural selection. It need not be so grand as to "build" anything. It may simply tweak or help in some way. By the way, I'd be happy to discuss microevolution, information, etc. futher, but this particular thread is getting a bit unwieldy. Perhaps an opportunity will arise elsewhere. answers.com: "“Microevolution = Evolution resulting from a succession of relatively small genetic variations that often cause the formation of new subspecies.”" I have problems with their answer. Firstly, the "formation of subspecies" part is unnecessary. And just what a "subspecies" is is a can of worms I don't even wish to come close to. The first part is okay, but I think one or two changes should be sufficient. No building required, in my mind, just change. [pause...]great_ape
March 22, 2007
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thanks for the paper reference, gpuccio. There was mention in the Jamaican paper of other curious findings about AS vs. AA relative transmission and fitness. the details of this particular study confuse me a little. They claim that directional selection may no longer be occurring against S, but what about SS homozygotes (i.e. sickle-cell), for which they show no maternity data for? Am I missing something? .... ack, okay, so they're suggesting you can't call it directional (as in one-directional) since there appears to be some force selecting *for* the AS genotype. So it's balancing selection. Although they're not sure. It would be interesting to see how strong this AS bias is compared to the deleterious of SS homozygotes.great_ape
March 22, 2007
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A few points: gpuccio, I appreciate your thoughtful comments. There are a few things I (conveniently) take as given because I extend a basic level of trust to my fellow scientists. If I did not, we would never get anywhere. When there appears sufficient reason for more skepticism, I'll provide it. I accept the premise that Africans from endemic malaria regions have higher S-allele incidents. I have read several scholarly articles to that effect, have heard it on TV, etc. So I have as much confidence in this as I do that Japan exists, even though I've never been there. Same goes for the protective effect of the SA genotype for malaria. Same for the reduction in fitness for the SS genotype (i.e. sickle-cell). Now I can reference papers for those things, but some would not be happy until they had all the raw data in their hands. (And some still wouldn't be happy until they collected it themselves.) I don't have time for all that so I work with certain reasonable premises, as, I imagine, most everyone does. You are right, the protection from SA is more "definitive" than the malaria natural selection hypothesis for *why* S-allele persists in the population at high frequency. But consider the fact that this only seems to be the case in malaria-endemic regions. Inference to best explanation, with a few other juicy tidbits (such as the child vs. adult genotype assymetry) thrown in to assist. Like I said earlier, I'm open to the idea that something else, in addition, helps prop up the S-allele, but I need to think through that further and, ultimately, it comes down to numbers. This *other* influence does not explain why the S-allele is more frequent in malaria-endemic regions and why it is found much more rarely elsewhere. That is the reason I remain skeptical as to how much influence this "propping up" force ultimately has. It clearly doesn't exert itself strongly outside of malaria-endemic regions. Which makes one wonder how much it exerts within. "A second important consideration is that we have a lot of other mendelian diseases which have persisted for very long times without any “microevolutionary” model to explain them." --gpuccio Good thought, but these mendelian diseases you mention are largely (a) recessive, such that, at low frequencies, they can "hide" in their heterozygote state silently. (b) complex, such that penetrance is not high (MS, Alzheimer's, Parkinson's, Schizophrenia, etc.) That is, a constellation of things determines if they'll manifest or not. (c) As in the case of alzheimers (by and large) manifestation occurs after reproductive age and thus has negligible effects on reproductive fitness. Natural selection, in this case, can no longer provide any assistance. [pause]great_ape
March 22, 2007
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"I am not so sure the model fitted the first 3/4s so much as much as it was calibrated relative to the assumptions of decline and the observations in the earlier study, with the decline thesis being assumed and seen as “verified” by the low incidence of S." --kairosfocus The paper's methods state the following, "an estimate for the relative fitness of women with HbSS was computed as the product of the number of predicted live births and the probability of survival to puberty...there is a delay in onset of puberty and first pregnancy among HbSS compared to HbAA individuals; thus survival to age 15 years approximates survival to puberty. An estimate for the relative fitness of men with HbSS was computed as the product of survival to puberty and one minus the cumulative probability of complete erectile dysfunction by the age of 15 years." It's not clear to me from their methods section if they use local data or other studies for calibration. (Presumably if they completely used local empirical data, their model should have more accurately predicted the *recent* allele decline, which is the opposite of what happened) Basically, when I say the model "fit" for the first 3/4 of the time period, I mean that, using those parameters, the 1973-1983 cohort allele frequencies were within the range expected if they had been declining according to the model's dynamic. Again, if this were an artifact of the fact they were using empirical Jamaican data, you'd expect to see the opposite of what they found. As to your horse race analogy. The more I think about it, the more I think there may be something to it. First, let me say that it really ultimately depends on the details of the other horses. It may well be that even though those alternative, less lethal allele types confer resistance to malaria as well, they may not do so as effectively/efficiently etc, as the S-allele. It also may be that they weren't available (i.e. present) in the appropriate populations. As the army folks say, a good plan now is better than the best plan a day too late. Just because we know of a multitude of variations of Hb doesn't mean those variants are/were present in malaria-endemic regions. Currently, for example, there is a heavy European bias in our genetic variation data. So the details of the competing horses are key. That said, there may be something to this increased AS transmission and infant health that "props up" the S-allele more so than its competitors. It has a head start in the race. Depending on just *how much* selection for malaria resistance is occurring, and *how much* selection against sickle -cell is occurring this head start for S may or may not be necessary for its persistence in the population. So it truly comes down to the numbers here. Yes, non-lethal variants can linger in the population as PaV suggested, but *deleterious* variants generally only linger at very low frequencies. (where homozygotes are very rarely seen outside of inbreeding) Here, we have populations where a known significantly deleterious allele (S) is at a relatively high frequency. So it's clear something else is going on; the question is what. For me the malaria resistance is evidently part of the story. I am now, however, somewhat more open to the idea that there's another element in the equation.great_ape
March 22, 2007
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"However, PaV has a degree in biology from a secular school. I wouldn’t be too quick to label him as illiterate in science." --PaV I didn't mean to suggest he is altogether illiterate. I do have considerable doubts about his familiarity with how science and scientific discourse is generally conducted. I find it extremely difficult to hold an intelligible conversation with someone with whom so very little common ground can be found. Statistics is a pillar of scientific discourse. (And yes, I know that the framework and assumptions are important). There are some basic criteria, which, once we abandon them, we might as well just be stating how we "feel" about the various concepts. It was my assumption that others here in the community would find many of his assertions and implications equally problematic. Basically, in sociological terms, I was looking for the community to help lay down some ground rules for what is taken as given and what is not. Skepticism is healthy. Seeking to undermine every premise offered is not healthy. It's one thing to be outnumbered here. It's another thing to be outnumbered and have to illustrate, on top of everything else, that Africans from malaria-endemic regions have a higher rate of sickle-cell anemia. For that kind of thing I expected other reasonably objective voices to lend a hand for the sake of maintaining a fruitful conversation. [end complaining]great_ape
March 22, 2007
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great_ape wrote: I’m not sure why you’d think the sickle-cell S-allele would necessarily fix or be lost rather than reaching an equilibrium with non-S (A).
You are correct. I mis-spoke. "Fixed" is the inccorect term. Thanks. Salscordova
March 22, 2007
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Salvador, I'm not sure why you'd think the sickle-cell S-allele would necessarily fix or be lost rather than reaching an equilibrium with non-S (A). Recall that the presence of the S-allele in *two* separate genotypes SA and SS, one of which is beneficial and one of which is detrimental, yields a dynamic where the negative nature of the SS type pulls down hard on S frequencies, but the positive SA type causes it to increase. How fast the S-allele frequency is moving up or down depends on several factors, including the relative frequency of S. (The higher the S-allele frequency, the higher the probability of deleterious SS homozygotes, leading to more rapid removal of S) You can solve for an equilibrium here where neither allele fixes. This is more or less what I think is occurring in malaria endemic regions. As to your question about estimating the degree of selection against S-allele (without malaria's influence), it's a good question. This would indicate how strong the malaria benefit of S would need to be to counter its effects. I need to check further into the details. "I would presume, the weaker the selection force, the larger the sample size is needed to establish the selection force exists to some level of confidence. Is that correct?" --Salvador I'd restate it as "the weaker the selection force, the larger the population size needs to be to counter the influence of stochastic genetic drift, such that the allele would *deterministically* decrease in frequency (all else being equal.)"great_ape
March 22, 2007
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By the way, was this other paper ever cited in the above discussion? Hum Biol. 2001 Aug;73(4):583-6. Protection afforded by sickle-cell trait (Hb AS): what happens when malarial selection pressures are alleviated? Hoff C, Thorneycroft I, Wilson F, Williams-Murphy M. Department of Pediatrics, School of Medicine, University of Utah, Salt Lake City, USA. Abstarct: A study of reproductive outcome in Mobile, AL was conducted among a large maternal cohort with sickle-cell disease (Hb SS), sickle-cell trait (Hb AS), and no hemoglobinopathies (Hb AA). It was found that mean gravidity and live births among Hb AS women were significantly higher than among Hb AA women. These findings were surprising since it is generally held that once malarial pressure is alleviated, any reproductive advantage that might be conferred by Hb AS would disappear and fertility levels would reach levels similar to or slightly less than that of Hb AA women. A search of the literature was subsequently conducted and a large cohort study of an African-derived population was found in the United Kingdom. Results from this study also showed that parity was significantly higher among Hb AS women compared to Hb AA women. If survivorship is similar among Hb AS and Hb SS women, findings from these two studies raise doubts whether directional selection is occurring against the Rb S allele in nonmalarial environments. Balancing selection may still be occurring.gpuccio
March 22, 2007
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great_ape, I want to express my appreciation for your participation here having to defend your position while being outnumbered. However, PaV has a degree in biology from a secular school. I wouldn't be too quick to label him as illiterate in science. I myself have said I think sickle-cell anemia might be fixed and was fully convinced of it before this thread began, so in a sense I had been favorable to your position on the issue. But in the course of this thread, I must concede I now think my initial position could be wrong. Fixing a mutation that is inherently deleterious is not easy. The pluses have to outweigh the negatives, and until that can be quantified, I would think all other factors being equal that a deleterious mutation would be selected against, not for. I do value your civil participation here and hope you continue to be a part of the UD community. But let's be scientific about this. As a controlled reference environment (where there is no malaria) what is the selection force against sickle-cell anemia? That will give how much selection force for sickle-cell anemia must be provided in a malaria environment. What would be the conditions that would be needed to make a definitive estimate? I don't think the definitions of controlled conditions and sufficient sampling size have even been defined. I would presume, the weaker the selection force, the larger the sample size is needed to establish the selection force exists to some level of confidence. Is that correct? Salvadorscordova
March 22, 2007
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great_ape: I am always available to discuss serenely scientific problems, especially if pertaining to method. I have read the discussions between you and PaV, and I have already tried to sum up my point of view in my previous post. I deeply respect both PaV and you, and with both of you I have had more than one satisfactory exchange. That does not imply that I necessarily agree with anybody else's point of view. For instance, although I can certainly share many of PaV's arguments, I do believe in statistical methodology, provided it is used well, while, if I understand well, he seems to be more skeptical about that subject. Indeed, scientific methodology and statistics are one of my main interests. Regarding your discussions about the S trait, I must confess that I was not very interested in the details, for two reasons: first, I have not checked all the available data source; second, my impression was that the object of the discussion was essentially irrelevant, because, as I have already stated in my previous post, the S trait, in my opinion, can tell us nothing about microevolution. Anyway, I will try to state again my tentative ideas on the subject, which consists of two separate hypotheses: a) S trait carriers are more rarely infected by malaria. As I have said, I tend to believe that, but I have not chacked all the available data, and I am not particularly motivated to do that. I have done a quick calculation in excel on the numbers you linked about africa, taken as a whole, performing a simple chi square, and the resulting p for the null hypothesis was very low, so I am statistically satisfied, but I have no idea if the data are methodologically correct, so I cannot give a final judgement. Anyway, let us say that we have a very likely association between the S trait condition and some protection from malaria infection, and we have also a possible explanatory model (a defective hemoglobin could well be a habdicap for the intracellular growth of the plasmodium). So, on this point I would tentatively agree with great ape, both in method and conclusions. b) S trait has persisted in time because of the selective pressure due to its positive effect on malaria infection risk. This second hypothesis is in no way a logical consequence of the first one, and has to be proved empirically. I am not sure we have evidence of it, although in principle I have no difficulty in admitting it could be true. But many models could be true, but are not true. Apart from the lack of strict evidence (but, again, I have not checked all the available data), I have some basic problems with "easy" explanations like that, which in part are similar to reservations expressed by PaV. One important factor is that we have many potential variables, in red blood cell phenotype and metabolism, which seem to influence susceptibility to malaria infection, and therefore the model is potentially very complex. A second important consideration is that we have a lot of other mendelian diseases which have persisted for very long times without any "microevolutionary" model to explain them. As far as I know, our understanding of the intrinsic mechanisms of generation and persistence of genetic diseases is still very superficial. So, to some up: with all the reservations due to my incomplete knowledge of the subject, my idea is that a) is probably true, while b) could be true, but is only a tentative hypothesis. But the important thing is that anyway b), even if it were true, is not an example of microevolution. You say that my issue is mainly semantic. Well, it is. Semantic is very important for me, because bas semantic is often a screen for bad thinking, and for hidden lies, like natural selections which don't "select" anything, or micorevolutions which don't "evolve" anything. So, lacking a clear definition of what microevolution should be, I will start form the following definition (from answers.com): "Microevolution = Evolution resulting from a succession of relatively small genetic variations that often cause the formation of new subspecies." Not very satisfying, indeed. So I will add your definition, which I like more: "For myself, and many others, evolution in its most straight-forward sense begins at the level of population genetics, where a beneficial trait increases in frequency and ultimately fixes in the population" Well, I will only comment that, according to those definitions, and especially yours, the S trait model is not an example of microevolution. The reasons: 1)Here we have no beneficial trait. As I have already said, S hemoglobin can in no way be considered a beneficial trait. It is a poorly functional molecule, indeed a "toxic" variant of normal hemoglobin (it is unstable, it precipitates in the RBC causing its deformation and ultimate death). In the homozygous form, it is quite incompatible with a long and healthy life, and in its heterozygous form it can be tolerated only because the normal allele can synthesize normal A hemoglobin, and is anyway a cause of problems and symptoms for the carrier. 2) The trai, anyway, has never become "fixed" in the population (thanks God!), in the sense of increasing its frequency and becoming the main allele. Even after a very long time, and even in countries where malaria infection is endemic, the S trait is a minor variation: it just survives, like many other mendelian diseases; it causes much suffering, but, luckily, it has created no new subspecies. So, if we want to discuss microevolution (and I am really intersted in that) I think you (I mean great ape, or anyone volunteering) shoud provide, in my opinion, some other, pertinent model.gpuccio
March 22, 2007
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Just a brief note and request for a favor. There are IMO several things wrong with PaV's recent (longish) post above. There are very basic problems there that transcend the evolution vs. ID debate. They deal with scientific methodology and basic scientific literacy. I feel it shouldn't be my sole responsibility to address each issue in detail, and it would be very fruitful for everyone if folks other than myself corrected some of the more egregious statements. Just because he ultimately shares the same position as you doesn't mean you can't challenge individual assertions. If there were a darwinist/evolutionist on this thread, I'd feel free--if not compelled--to criticize anything they posted that I believed incorrect.great_ape
March 22, 2007
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I'll be waiting.kairosfocus
March 22, 2007
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Much has been written since my last post; I will try to respond, where possible, in the next day or so. But one thing quickly for gpuccio: "But even so, I have real difficulties to consider them as examples of “minimal” evolution. " --gpuccio In this case, I think your issue is largely semantic. For myself, and many others, evolution in its most straight-forward sense begins at the level of population genetics, where a beneficial trait increases in frequency and ultimately fixes in the population. What began as rare becomes characteristic. Thus selection at the level of the population is evolution, or microevolution. The S-allele case discussed above has a twist because, if Haldane is correct, the negative effects of the homozygote S genotype prevent the S-allele from fixing. However, the forces at work are, at heart, that which Darwin outlined as the basic algorithm of natural selection. Which is why I think natural selection/microevolution is appropriate nomenclature.great_ape
March 21, 2007
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gpuccio: c) The “advantage” provided by the mutation is always related to the loss of information, which “interferes” with a specific, “intelligent” aggression from some agent (antibiotics, pesticides, plasmodia). In other words, the “disease” provides an indirect “escape” from some enemy, because it changes (in a degenerative sense) the target of the aggression. This is clear in all three conditions.PaV
March 21, 2007
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H'mm: Let n me at least try to get though this much quickly [also, testing the filter]: ___________ 4] distinguish *where* the curve was flat from where the prediction fit, which is the majority of the time period in question >= 75%. I am not so sure the model fitted the first 3/4s so much as much as it was calibrated relative to the assumptions of decline and the observations in the earlier study, with the decline thesis being assumed and seen as “verified” by the low incidence of S. I find this seems to be hinted at in the following phrasing in the abstract:
To evaluate the determinants of, and derive expected values for, sickle allele frequency in Jamaica, local empirical data were used to estimate the parameters of deterministic models of allele frequency decline. We found that although model predictions were broadly consistent with observed values in the 1973-1981 cohort, the predicted change in allele frequency between the two cohorts was larger than the observed, nonsignificant, reduction. Close agreement between predicted and observed values was only achieved by simulating a recent, marked increase in HbSS fitness.
The onward projection was that the trend should more or less continue, but: the "unexpected" persistence of the sickle allele in Jamaica may reflect the fact that the actual fitness among SS individuals is higher than that previously realized. In turn, that fits in more with PaVs thought that the basic point is that variants that are sufficiently non-lethal [“survival of the fittest”] will be retained in the pop. You will note that in my last comment I split the difference, seeing that both theses may have a point: some protective effect, some residual naturally persistent survival level. I am also asking why is there not another horse that has won the race, if it has been ongoing for as long as the evo models of human origins assert. _____________ GEM of TKIkairosfocus
March 20, 2007
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