The pandemic virus as evolution professor

Like it or not, the pandemic virus (SARS-CoV-2) is giving us all lessons in evolution and natural selection. The latest is one of the clearest examples of natural selection you are likely to see.  It is very clear cut, but to leave almost no one behind, I’m going to put in a lot of background material which will bore the cognoscenti — they can skip all this and go to the meat of the issue after the ****

The genetic code is read in groups of 3.  Imagine a language in which all words must be 3 letters long. 

The dog ate the fat cat who bit the toe off one mad rat.   Call this the reading frame, in which the words all make sense to you

Any combination of 3 letters means something to the machinery inside the cell responsible for reading the code, so deleting the f in fat 

gives us 

The dog ate the atc atw hob itt het oeo ffo nem adr at.   So this is a shift of 1 from the reading frame.  While it may not make sense to you, it makes sense to the cellular machinery. 

Now let’s delete 2 letters (in a row)

The dog ate the fat cat who bit the tof fon ema dra t.  

Not much sense after the deletion is there?  Or at least a completely different message.  This is a shift of 2 from the reading frame.

Now 3 letters (in a row)

The dog ate the fat cat who bit the toe off one mad rat.  

This gives 

The dog ate the fat cat who bit the tff one mad rat.  

Which has a funny looking word (tff), but leaves the rest of the 3 letter words intact (one mad rat).  This is called an in frame deletion. It basically lops out a single 3 letter word.  

Lopping out 4, 5, 6, .. letters will just give you one of the 3 patterns (frame shift of 1, frame shift of 2 or no frameshift at all) shown above (but nothing new)

*****

Now the business end of the pandemic virus is the spike protein, and these are where the mutations everyone is worried about occur.  The spike protein binds to another protein (ACE2) on the surface of human cells and then the virus enters causing havoc.  All the vaccines we have are against the spike protein. 

The spike protein is big (1,273 different 3 letter words).  

Mutations occur randomly.  We now have something called GISAID (Global Initiative on Sharing All Influenza Data) which has well over 100,000 genome sequences of the virus.  

Other things being equal we should see as many 1,  4 (3+1), 7 (2*[3] + 1), 10 letter deletions as 2, 5 (3 + 2), 8 ( 2*[3] + 2) , as 3, 6, 9, 12, letter   deletions.

The set  1, 4, 7, 10, . . represents a shift of 1 from the original reading frame, the set 2, 5, 8, 11 … represents a frame shift of two and 3, 6, 9 .. represents a set of deletions producing no frameshift at all.

Since thousands on thousands of experiments show that mutations occur randomly, 1/3 of all deletion mutations should show a frameshift of 1, 1/3 of all deletion mutations should have a frame shift of 2, and 1/3 of all deletion mutations should produce no frameshift at all. 

Well the authors of Science vol. 371 pp. 1139 – 1142 ’21  looked at 146,795 viral sequences and found 1,108 deletions in the gene for the spike protein.

They did not find each of the 3 types of deletions occuring to the same extent (1/3 of the time).  Among all deletions, 93% were in frame.  

Why? Because out of frame deletions change everything that comes after them. 

Recall

The dog ate the atc atw hob itt het oeo ffo nem adr at.  

This means that a functional spike protein won’t be formed, and the virus won’t infect our  cells, and it certainly won’t be found in GISAID.  

Ladies and Gentlemen you have just witnessed natural selection in action. 

Actually it’s even more complicated and even more impressive than that.  The in frame deletions occurred in one of four areas, which happen to be where antibodies to the spike protein bind.  So the out of frame deletions were selected against, and the in frame deletions were selected for. 

The blind watchmaker in action.

Another way to see how improbable it is that random choice should choose one of 3 equally probable possibilities 97% of the time, imagine that you are throwing dice.  You throw a single dye 100 times, and 97 times you get either of two numbers (say 3 and 6) .  You know the dye is loaded.  The load being natural selection in the case of genome deletions. 

 

 

 

 

 

Virus 1 Astra Zenica vaccine 0

It’s already happened. A mutated pandemic virus has rendered a vaccine useless. This is serious — the game of cat and mouse with the mutating pandemic virus (otherwise known as natural selection) has begun. You can read all about it here

https://www.sciencemag.org/news/2021/02/south-africa-suspends-use-astrazenecas-covid-19-vaccine-after-it-fails-clearly-stop?utm_source=Nature+Briefing&utm_campaign=6ada806177-briefing-dy-20210208&utm_medium=email&utm_term=0_c9dfd39373-6ada806177-46043190

For a leisurely stroll through the background needed to understand the Science and Nature articles I’m going to essentially republish (and refurbish) a very recent  post — trying to make things as accessible as possible. 

The human species as a culture medium for the pandemic virus

Creationists or not, we are all about to get an unwanted lesson in natural selection and evolution, courtesy of the current pandemic virus (SARS-CoV-2).  This is going to be a long post, which will contain an incredible case of meningitis, thoughts on selfish genes in viruses, evolution, natural selection and why we’re in for a very, very long haul with the pandemic virus.

As you probably know, mutant pandemic viruses (all different) have emerged (in England, South Africa, Brazil).  Even worse they appear to be more infectious, and some are more resistant to our vaccines (all of which were made before they appeared).  

Here is lesson #1 in natural selection.  Viruses have no brains, they barely have a genome.  The human genome contains 3 billion positions, the pandemic virus 30,000.  So we have 100,000 times more information in our genome than the virus does. 100,000 is about the number of inches in a mile and half.  

So how is the virus outsmarting us?  Simply by reproducing like mad.  The molecular machines that copy our genome are very accurate, making about 1 mistake per 100,000,000 positions copied — that’s still enough for the average newborn to have 30 new mutations (more if the parents are older).  The viral machine is much less accurate.  So lots of genome mutations are made (meaning that the viral proteins made from the genome change slightly).  Those that elude the vaccines and antibodies we’re throwing at them survive and reproduce, most don’t.  This is natural selection in action. Survival of the fittest.  Darwin wasn’t kidding.

What is so remarkable about the British and the South African variants, is that they contain multiple mutations (23 in the British variant, at least 3 in the South African variant).  Usually its just one or two.

 You’ve probably heard about the mutation changing just one of the 147 amino acids  in hemoglobin to cause sickle cell anemia. Here’s another.  APOE is a 299 amino acid protein.  It comes in 3 variants  — due to changes at 2 positions.  One variant greatly increases the risk of Alzheimer’s disease, another decreases it.  So even single mutations can be quite powerful. 

So how did these multiple mutations come about?  We likely now have an answer due to one very well studied case [ Cell vol. 183 pp. 1901 – 1912 ’20 ] in an immunocompromised patient with chronic lymphatic leukemia (CLL). She shed the virus for 70 days.  Even so, she wasn’t symptomatic, but because the patient had enough immune system to fight the virus to a draw, it persisted, and so its genome was always changing.  The authors were smart enough to continually sequence the viral genome throughout the clinical course and watch it change.  So that’s very likely how the virus accumulates mutations, it lived for a long time in a patient who lived a long time with a weakened immune system allowing the virus to merrily mutate without being killed and allowing the weakened immune system to effectively select viruses it can’t kill. 

Could this happen again? Of course.   There are some 60,000 new cases of CLL each year in the USA.  Many of them have abnormal immune systems even before chemotherapy begins.

Here is an example from my own practice. The patient was a 40 year old high school teacher who presented with severe headache, stiff neck and drowsiness.  I did a spinal tap to get cerebrospinal fluid (CSF) for culture so we could find the best possible antibiotic to treat the organism.  This was 30+ years ago, and we had no DNA testing to tell us immediately what to do.  We had to wait 24 hours  while the bugs grew in culture to form enough that we could identify the species and determine  the antibiotics it was sensitive to. . 

As the fluid came out, I had a sinking feeling; as it was cloudy, implying lots of white cells fighting the infection. Enough white cells to make CSF cloudy (it normally looks like water) is a very bad sign. So after starting the standard antibiotic to be used in the first 24 hours before the cultures came back, I called the lab for the cell count.  They said there weren’t any.  I thought they’d seriously screwed up maybe losing what I’d sent or mislabeling it and looking at the wrong sample, and I unpleasantly stormed down to the lab (as only an angry physician can do) to see the spinal fluid.  They were right.  The cloudiness of the CSF was produced by hordes of bacteria not white cells.  This was even worse as clearly the bacteria were winning and the patient’s immune system was losing, and I never expected the patient to survive.  But survive he did and even left the hospital.  

Unfortunately, the meningitis turned out to be  the first symptom of an abnormal immune system due to a blood malignancy — multiple myeloma. 

****

Addendum 2 February — I sent this post to an old friend and college classmate who is now a hematology professor at a major med school.  He saw a similar case —

“When I was a medical student I saw a pediatric sickle anemia patient (asplenic) with fever and obtundation. When I looked at the methylene-blue stained CSF, I thought that stain had precipitated. So I obtained a fresh bottle of stain and it looked the same. Only this time, I looked more closely and what I thought was precipitated stain were TNTC pneumococci.

I urge all my immunosuppressed patient to get vaccinated for covid-19. I worry that if many people don’t get vaccinated,  those who do will not be that better off.”

Addendum 3 February– I asked him if his patient had survived like mine —

answer 

“Unfortunately, no. With the pneumococcus, If antibiotics are not started within 4 hours after recognition, the train has left the station.”

 

****

So there are millions of active cases of the pandemic, and tons of people with medical conditions (leukemia, multiple myeloma, chemotherapy for other cancer) with abnormal immune systems, just waiting for the pandemic virus to find a home and proliferate for days to weeks.  Literally these people are culture media for the virus. Not all of them have been identified, so don’t try to prevent this by withholding vaccination from the immunocompromised — they’re the ones who need it the most. 

I think we’re in for a very long haul with the pandemic.  We’re just gearing up to stay on top of the viral sequence du jour.   Genome sequencing is not routine (it should be).  The South African and British mutations were picked up because a spike in cases led people to sequence the virus from these patients.  Viral genome sequencing and surveillance should be routine in most countries and should not wait for an infection spike to occur. 

You may come across the terms B.1.351 and  507Y.V2 — they are different names for the South African virus which beat Astra Zenica.  The British variant is also called B.1.1.7

The human species as a culture medium for the pandemic virus

Creationists or not, we are all about to get an unwanted lesson in natural selection and evolution, courtesy of the current pandemic virus (SARS-CoV-2).  This is going to be a long post, which will contain an incredible case of meningitis, thoughts on selfish genes in viruses, evolution, natural selection and why we’re in for a very, very long haul with the pandemic virus.

As you probably know, mutant pandemic viruses (all different) have emerged (in England, South Africa, Brazil).  Even worse they appear to be more infectious, and some are more resistant to our vaccines (all of which were made before they appeared).  

Here is lesson #1 in natural selection.  Viruses have no brains, they barely have a genome.  The human genome contains 3 billion positions, the pandemic virus 30,000.  So we have 100,000 times more information in our genome than the virus does. 100,000 is about the number of inches in a mile and half.  

So how is the virus outsmarting us?  Simply by reproducing like mad.  The molecular machines that copy our genome are very accurate, making about 1 mistake per 100,000,000 positions copied — that’s still enough for the average newborn to have 30 new mutations (more if the parents are older).  The viral machine is much less accurate.  So lots of genome mutations are made (meaning that the viral proteins made from the genome change slightly).  Those that elude the vaccines and antibodies we’re throwing at them survive and reproduce, most don’t.  This is natural selection in action. Survival of the fittest.  Darwin wasn’t kidding.

What is so remarkable about the British and the South African variants, is that they contain multiple mutations (23 in the British variant).  Usually its just one or two.

 You’ve probably heard about the mutation changing just one of the 147 amino acids  in hemoglobin to cause sickle cell anemia. Here’s another.  APOE is a 299 amino acid protein.  It comes in 3 variants  — due to changes at 2 positions.  One variant greatly increases the risk of Alzheimer’s disease, another decreases it.  So even single mutations can be quite powerful. 

So how did these multiple mutations come about?  We likely now have an answer due to one very well studied case [ Cell vol. 183 pp. 1901 – 1912 ’20 ] in an immunocompromised patient with chronic lymphatic leukemia (CLL). She shed the virus for 70 days.  Even so, she wasn’t symptomatic, but because the patient had enough immune system to fight the virus to a draw, it persisted, and so its genome was always changing.  The authors were smart enough to continually sequence the viral genome throughout the clinical course and watch it change. 

Could this happen again.  Of course?   There are some 60,000 new cases of CLL each year in the USA.  Many of them have abnormal immune systems even before chemotherapy begins.

Here is an example from my own practice. The patient was a 40 year old high school teacher who presented with severe headache, stiff neck and drowsiness.  I did a spinal tap to get cerebrospinal fluid (CSF) for culture so we could find the best possible antibiotic to treat the organism.  This was 30+ years ago, and we had no DNA testing to tell us immediately what to do.  We had to wait 24 hours  while the bugs grew in culture to form enough that we could identify the species and determine  the antibiotics it was sensitive to. . 

As the fluid came out, I had a sinking feeling; as it was cloudy, implying lots of white cells fighting the infection. Enough white cells to make CSF cloudy (it normally looks like water) is a very bad sign. So after starting the standard antibiotic to be used in the first 24 hours before the cultures came back, I called the lab for the cell count.  They said there weren’t any.  I thought they’d seriously screwed up maybe losing what I’d sent or mislabeling it and looking at the wrong sample, and I unpleasantly stormed down to the lab (as only an angry physician can do) to see the spinal fluid.  They were right.  The cloudiness of the CSF was produced by hordes of bacteria not white cells.  This was even worse as clearly the bacteria were winning and the patient’s immune system was losing, and I never expected the patient to survive.  But survive he did and even left the hospital.  

Unfortunately, the meningitis turned out to be  the first symptom of an abnormal immune system due to a blood malignancy — multiple myeloma. 

****

Addendum 2 February — I sent this post to an old friend and college classmate who is now a hematology professor at a major med school.  He saw a similar case —

“When I was a medical student I saw a pediatric sickle anemia patient (asplenic) with fever and obtundation. When I looked at the methylene-blue stained CSF, I thought that stain had precipitated. So I obtained a fresh bottle of stain and it looked the same. Only this time, I looked more closely and what I thought was precipitated stain were TNTC pneumococci.

I urge all my immunosuppressed patient to get vaccinated for covid-19. I worry that if many people don’t get vaccinated,  those who do will not be that better off.”

Addendum 3 February– I asked him if his patient had survived like mine —

answer 

“Unfortunately, no. With the pneumococcus, If antibiotics are not started within 4 hours after recognition, the train has left the station.”

 

****

So there are millions of active cases of the pandemic, and tons of people with medical conditions (leukemia, multiple myeloma, chemotherapy for other cancer) with abnormal immune systems, just waiting for the pandemic virus to find a home and proliferate for days to weeks.  Literally these people are culture media for the virus. Not all of them have been identified, so don’t try to prevent this by withholding vaccination from the immunocompromised — they’re the ones who need it the most. 

I think we’re in for a very long haul with the pandemic.  We’re just gearing up to stay on top of the viral sequence du jour.   Genome sequencing is not routine (it should be).  The South African and British mutations were picked up because a spike in cases led people to sequence the virus from these patients.  Viral genome sequencing and surveillance should be routine in most countries  — not waiting on an infection spike. 

 

 

Natural selection yes, but for what?

Groups across the political spectrum don’t like the idea that natural selection operates on us. The left because of the monstrosities produced by social Darwinism and eugenics. The devout because we have supposedly been formed by the creator in his image and further perfection is blasphemous.

Like it or not, there is excellent evidence for natural selection occurring in humans. One of the best is natural selection for the lactase gene.

People with lactose intolerance have nothing wrong with the gene for lactase which breaks down the sugar lactose found in milk.  Babies have no problem with breast milk.  The enzyme (lactase)  produced from the gene is quite normal in all of us; no mutations are found in the lactose protein.  However 10,000 years ago and earlier, cattle were not domesticated, so there was no dietary reason for a human weaned from the breast to make the enzyme.  In fact continuing to use energy to make the enzyme something it would never get to act on is wasteful. The genomes of our ancient ancestors had figured this out.   The control region (lactase enhancer) for the lactase gene is 14,000 nucleotides upstream from the gene itself, and back then it shut off after age 8.  After domestication of cattle 10,000 or so years ago, so that people could digest milk their entire lives a mutation arose changing cytosine to thymine in the enhancer. It spread like wildfire because back then our ancestors were in a semi-starved state most of the time, and carriers of the mutation had better nutrition.

Well that was the explanation until a recent paper [ Cell vol. 183 pp. 684 – 701 ’20 ]. It was thought that lacking the mutation you couldn’t use milk past age 8 or so. However sequencing of sites of the herdsmen of the steppes showed that they were using milk a lot (making cheese and yogurt) 8,000 years ago. Our best guess is that the mutation arose 4,000 years ago.

So possibly, the reason it spread wasn’t milk digestion, but something else. Nothing has changed the million nucleotide segment of our genome since the mutation arose — this implies that it was under strong positive natural selection. But for what?

Well, a million nucleotides codes for a lot of stuff, not just the lactase enzyme. Also there is evidence that people with the mutation is linked to metabolic abnormalities and diseases associated with decreased energy expenditure, such as obesity and type II diabetes, as well as abnormal blood metabolites and lipids.

The region codes for a microRNA (miR-128-1). Knocking it out in mice results in increases energy expenditure and improvement in high fat diet obesity. Glucose tolerance is also improved.

So it is quite possible that what was being selected for was the ‘thrifty gene’ miR-128-1 which would our semi-starved ancestors expend less energy and store whatever calories they met as fat.

In cattle a similar (syntenic) genomic region near miR-128-1 has also been under positive selection (by breeders) for feed efficiency and intramuscular fat.

So a mutation producing a selective advantage in one situation is harmful in another.

Another example — https://luysii.wordpress.com/2012/06/10/have-tibetans-illuminated-a-path-to-the-dark-matter-of-the-genome/

The mutation which allows Tibetans to adapt to high altitude causes a hereditary form of blindness (Leber’s optic atroxpy) in people living at sea level. 25% of Tibetans have the mutation. Another example of natural selection operating on man.

The wages of inbreeding

Saguenay Lac St. Jean is a beautiful region of Quebec. It’s fairly isolated. Once you get to the top of the lake there is no way that you can drive farther north (no road).  We spent part of our 25th anniversary there.  The population bears a heavy load of genetic disease (through no fault of their own).

The reason is historical. Only 8,000 people emigrated from France to Quebec between 1608 and 1763. After the English victory that year  only 1,000 emigrated in the next 90 years.  In 1992, the population of the Saguenay  region was around 300,000 and Quebec itself 2,000,000.

This means that once the population began expanding with relatively little outside input, recessive genes began to meet each other, as in a large population there are so many more ways to make this happen than in a small one.

To keep the the nonBiologists reading this aboard, here is what recessive means. Our genome has 46 chromosomes.  We all have two sex chromosomes (either X and Y or X and X).  The other 44 chromosomes come in pairs.  This gives you two copies of each gene.  The classic recessive gene is that for sickle cell anemia.  If just one of the pair has the Sickle trait you are OK, if both have it, you have sickle cell anemia (which you definitely don’t want to have).  Actually if you live in Africa it is better if you have one gene with the trait as it makes you more resistant to Malaria.  This is why the trait became so common in Africans.  It’s natural selection in action (and in a human population to boot).  Just one good sickle gene (not carrying the trait) is enough to mask the effects of the bad gene, so the carrier is normal.   This is why sickle cell trait is called a recessive gene.

Here is one example.  The incidence of a muscle disease (myotonic dystrophy) worldwide is 2 – 14/100,000.  In the Saguenay region it is 189/100,000.

Even 20 years ago, the carrier frequency of many genetic disorders up there was quite high [ Proc. Natl. Acad. Sci. vol. 95 pp. 15140 – 15144 ’98 ]

Spastic ataxia 1/21

Type I tyrosinemia 1/22

Sensorimotor polyneuropathy 1/23

Pseudovitamin D deficient rickets 1/26

Cytochrome C oxidase deficiency 1/26

Cystinosis 1/39

Histidase 1/32

Lipoprotein lipase 1/43

Pyruvic kinase 1/64

Then again, there are all sorts of genetic diseases found only in this region.

Similar conditions may apply to the ancestors of today’s native Americans — for details see the previous post — https://luysii.wordpress.com/2019/07/16/the-initial-native-americans-were-quite-inbred/.  Incredible as it may sound, the rape and pillage of the conquistadores may have actually been good from a genetic point of view.  Similar considerations may apply to any pair of populations meeting each other for the first time.  Hard stuff indeed, but you can’t repeal biology.

So, from a genetic point of view, it’s good if you reproduce with someone from a different group.  It’s why I’m glad to have a Chinese daughter in law, 2 grand-nephews whose father is Hindu, and a Russian woman about to marry our nephew.

 

 

The most interesting thing to an evolutionist is not that APOE4 increases the risk of Alzheimer’s disease

Neurologists were immensely excited by the discovery 25 years ago that the APOE4 variant of APOlipoprotein E increases the risk of Late Onset Alzheimer’s Disease (LOAD). 24,000 papers later (Google Scholar) we still don’t know how it does it. Should all this work have been done ? Of course ! !  Once we know the mechanism(s) by which APOE4 increases Alzheimer’s risk we’ll have new ideas to help us attack.

The APOE gene has 3 variants (alleles) APOE2, 3 and 4. The protein is average sized (299 amino acids). The 3 alleles differ at two positions (amino acids #112 and #158) where either cysteine or arginine can be found. The frequency of APOE4 is 14% in the adult white population, that of E3 is 78% and that of E2 is 8%.

Fascinating as this all is, it’s not what’s interesting from an evolutionary point of view.

[ Proc. Natl. Acad. Sci. vol. 113 pp. 17 – 18, 74 – 79 ’16 ] Postmenpausal longevity in females is not limited to humans. Humans, orcas and pilot whales are the only vertebrate species known to have prolonged postreproductive lifespans. Our fertility ends at about the same age that fertility ends in other female hominids (the great apes). However, apes rarely live into their 40s (even in captivity).

Unlike APOE4, APOE2 and APOE3 protect against late onset Alzheimer’s.

The fascinating point is that APOE2 and APOE3 aren’t found in the great apes. They are a human invention. Now LOAD occurs well past reproduction, so there should be no reason in terms of reproductive success for them to arise and be more common in human populations than the original APOE4.

Even more interesting is some work on another protein CD33, found on immune cells and glia in the brain [ Neuron vol. 78 pp. 575 – 577, 631 – 643 ’13 ] A minor allele (21% frequency in human populations) of CD33 (SNP rs 3865444) protects against Alzheimer’s. The allele is associated with reductions in CD33 expression in microglia, and also with reduction in levels of insoluble Abeta42 in (Alzheimer’s) brain. The numbers of CD33+ microglia correlate with insoluble Abeta42 levels and amyloid plaque burden. So decreasing (or inhibiting) CD33 function might help Alzheimer patients.

Again the protective allele is only found in man. The great apes don’t have it just the major (nonprotective) allele.

Again, there is no way that having the allele directly improves your reproductive success. By the time it is protecting you, you’re infertile.

What in the world is going on? Why did alleles protective against Alzheimer’s arise in two very different proteins in the course of human evolution?

“There is something fascinating about science. One gets such wholesale returns of conjecture out of such a trifling investment of fact.” — Mark Twain.

The reason these alleles probably arose gets us in to an ancient battle in evolutionary theory — what is the actual unit of selection? It may be the group rather than the individual. Face it, human infants and children are helpless for longer than other primates, and need others to care for them, for at least 5 years. Who better than grandma and grandpa? So the fact that with granny around more children survive to reproduce constitutes group selection (I think).

As Theodosius Dobzhansky said “Nothing in Biology Makes Sense Except in the Light of Evolution”

Is natural selection disprovable?

One of the linchpins of evolutionary theory is that natural selection works by increased reproductive success of the ‘fittest’. Granted that this is Panglossian in its tautology — of course the fittest is what survives, so of course it has greater reproductive success.

So decreased reproductive success couldn’t be the result of natural selection could it? A recent paper http://www.sciencemag.org/content/348/6231/180.full.pdf says that is exactly what has happened, and in humans to boot, not in some obscure slime mold or the like.

The work comes from in vitro fertilization which the paper says is responsible for 2 -3 % of all children born in developed countries — seems high. Maternal genomes can be sequenced and the likelihood of successful conception correlated with a variety of variants. It was found that there is a strong association between change in just one nucleotide (e.g. a single nucleotide polymorphism or SNP) and reproductive success. The deleterious polymorphism (rs2305957) decreases reproductive success. This is based on 15,388 embryos from 2,998 mothers sampled at the day-5 blastocyst stage.

What is remarkable is that the polymorphism isn’t present in Neanderthals (from which modern humans diverged between 100,000 and 400,000 year ago). It is in an area of the genome which has the characteristics of a ‘selective sweep’. Here’s the skinny

A selective sweep is the reduction or elimination of variation among the nucleotides in neighbouring DNA of a mutation as the result of recent and strong positive natural selection.

A selective sweep can occur when a new mutation occurs that increases the fitness of the carrier relative to other members of the population. Natural selection will favour individuals that have a higher fitness and with time the newly mutated variant (allele) will increase in frequency relative to other alleles. As its prevalence increases, neutral and nearly neutral genetic variation linked to the new mutation will also become more prevalent. This phenomenon is called genetic hitchhiking. A strong selective sweep results in a region of the genome where the positively selected haplotype (the mutated allele and its neighbours) is essentially the only one that exists in the population, resulting in a large reduction of the total genetic variation in that chromosome region.

So here we have something that needs some serious explaining — something decreasing fecundity which is somehow ‘fitter’ (by the definition of fitness) because it spread in the human population. The authors gamely do their Panglossian best explaining “the mitotic-error phenotype (which causes decreased fecundity) may be maintained by conferring both a deleterious effect on maternal fecundity and a possible beneficial effect of obscured paternity via a reduction in the probability of successful pregnancy per intercourse. This hypothesis is based on the fact that humans possess a suite of traits (such as concealed ovulation and constant receptivity) that obscure paternity and may have evolved to increase paternal investment in offspring.

Nice try fellas, but this sort of thing is a body blow to the idea of natural selection as increased reproductive success.

There is a way out however, it is possible that what is being selected for is something controlled near to rs2305957 so useful, that it spread in our genome DESPITE decreased fecundity.

Don’t get me wrong, I’m not a creationist. The previous post https://luysii.wordpress.com/2015/04/07/one-reason-our-brain-is-3-times-that-of-a-chimpanzee/ described some of the best evidence we have in man for another pillar of evolutionary theory — descent with modification. Here duplication of a single gene since humans diverged from chimps causes a massive expansion of the gray matter of the brain (cerebral cortex).

Fascinating

Addendum 13 April

I thought the following comment was so interesting that it belongs in the main body of the text

Handles:

Mutations dont need to confer fitness in order to spread through the population. These days natural selection is considered a fairly minor part of evolution. Most changes become fixed as the result of random drift, and fitness is usually irrelevant. “Nearly neutral theory” explains how deleterious mutations can spread through a population, even without piggybacking on a beneficial mutation; no need for panglossian adaptive hypotheses.

Here’s my reply

Well, the authors of the paper didn’t take this line, but came up with a rather contorted argument to show why decreased fecundity might be a selective advantage, rather than just saying it was random drift. They also note genomic evidence for a ‘selective sweep’ — decreased genomic heterogeneity around the SNP.