More detecting natural selection
A New Approach for Using Genome Scans to Detect Recent Positive Selection in the Human Genome
The evolution of new functions and adaptation to new environments occurs by positive selection, whereby beneficial mutations increase in frequency and eventually become fixed in a population. Detecting such selection in humans is crucial for understanding the importance of past genetic adaptations and their role in contemporary common diseases. Methods have already been developed for detecting the signature of positive selection in large, genome-scale datasets (such as the “HapMapâ€). Positive selection is expected to more rapidly increase the frequency of an allele, and hence, the length of the haplotype (extent of DNA segment) associated with the selected allele, relative to those that are not under selection. Such methods compare haplotype lengths within a single population. Here, we introduce a new method that compares the lengths of haplotypes associated with the same allele in different populations. We demonstrate that our method has greater power to detect selective sweeps that are fixed or nearly so, and we construct a statistical framework that shows that our method reliably detects positive selection. We applied our method to the HapMap data and identified approximately 500 candidate regions in the human genome that show a signature of recent positive selection. Further targeted studies of these regions should reveal important genetic adaptations in our past.
I’m in a hurry/busy, so no real comment. It’s PLOS, so it’s free. Read it.
beneficial mutations increase in frequency and eventually become fixed in a population. Detecting such selection in humans is crucial for understanding the importance of past genetic adaptations and their role in contemporary common diseases.
I have an honest, fundamental question and I doubt it needs a lengthy answer. Why do some researchers believe that evolution selects towards genes that cause common diseases? If evolution favors strength why should we suspect that heritable genes spread weakness? I’m not refering to examples like Heterozygote Advantage or rare genetic disorders.
A pathogenic explanation for fitness reducing conditions only takes one sentence. Pathogens cause damage and they are in competition against us. There must be a simple theory that explains why our own heritable genes would commonly turn on us.
btw, 500 recent adaptions? Interesting.
I’m thinking that the most recent post on hypertension should provide a partial answer to your question.
Three other short answers:
- the creature design space is full of tradeoffs; we might need to accept an increased risk of disease later in life in order to maximize our reproductive fitness
- we’re living in an environment rather different than the one we evolved in, so we could have genetically mediated vulnerabilities to disease that wouldn’t have manifested themselves in premodern times. Diabetes comes to mind (note the researchers say: ‘past adaptations … contemporary diseases’).
- even if the disease-causing variants were a minor part of the genetic landscape revealed by this analysis, the researchers would be well served (financially) by emphasizing this part of the findings :-)
the creature design space is full of tradeoffs; we might need to accept an increased risk of disease later in life in order to maximize our reproductive fitness
Good point, makes sense. I could see how that applies to genes like BRCA1 and 2 that tend to cause breast cancer in women after age 50. Maybe they offer some reproductive benefit as well?
we’re living in an environment rather different than the one we evolved in, so we could have genetically mediated vulnerabilities to disease that wouldn’t have manifested themselves in premodern times.
Makes sense. Big cities are full of gunk that we might not have evolved to resist.
the researchers would be well served (financially) by emphasizing this part of the findings
That might be your best explanation. 8-)
bbartlog
Thanks for your answer. Could I ask you one more question along the same lines? This one is easier and possibly more entertaining than the last one. 8-)
Genetic trigger Vs. Environmental trigger cage match!
Without revelaing the name of the condition if I gave you a few key pieces of information about it could you guesstimate some Las Vegas odds on the cause?
This fitness reducing condition is congenital.
This condition only effects the reproductive system and reduces the number of offspring produced by aproximately 80% when compared to controls.
Four studies put the monozygotic twin concordence rate at aproximately 20%.
Around 2% of the general population has this condition. Some research suggests the possibility that it is more common among people born in urban environments.
Genetic or Environmental?
I know that both play a role in everything but which would you guess is the driver.
2 to 1 genes, 2 to 1 environmental, 10 to 1 either? Which side does the smart money bet on?
evolution selects towards genes that cause common diseases? If evolution favors strength why should we suspect that heritable genes spread weakness?
evolution doesn’t favor “strength”, it favors fertility. all of bbartlog’s points are relevant.
about funding: yes, people like to write about disease because it brings them money. but it’s actually a valid thing it bring up– consider that the human genome has 3.3 billion base pairs. one goal of genetics is to determine which parts of the genome are functional. using only sequence data, there are generally two approaches– look for highly conserved regions, and look for regions under selection.
Without revelaing the name of the condition if I gave you a few key pieces of information about it could you guesstimate some Las Vegas odds on the cause?
haha, looc, I can guess the condition. genetics and environment aren’t mutually exclusive! and intra-uterine environment is also considered “environmental” without being part of what people usually think of as the environment.
p-ter
You probably guessed it, please don’t give the condition away. As soon as someone figures it out ideology enters and logic tends to exit.
“intra-uterine environment is also considered “environmental” without being part of what people usually think of as the environment“
Agreed.
I am no expert on genetics but I have to disagree with a statement you made.
evolution doesn’t favor “strength”, it favors fertility.
Shouldn’t that read fitness, not fertility? I was watching a National Geographic special on the Galapagos Islands a few nights ago. Evolution was doing a lot more than producing more or less babies. A specific example would be owls that had AMAZING camouflage. Another one would be birds that lost their wings and learned to swim.
This condition only affects the reproductive system
Even taking a rather broad view of ‘reproductive system’ I think this is incorrect.
Anyway, if both genes and environment play a role, then perception as to which is the ‘driver’ is going to depend on the environment and the frequency of the genes in question. A condition which is genetically rare (say 3% are homozygous for something) where the necessary environmental conditions are common (85% encounter the also needed trigger environment) is going to be seen as purely genetic. Reverse the percentages and you’re talking about something that will be seen as purely environmental. Autism *may* be an example of the former while AIDs could be viewed as the latter. But in both cases the perception is an outcome of our simplified model of cause and effect…
Lots of room in between, and generally I think the pragmatic thing is just to look at what we can change – which until recently has mostly been the environment, but now the game is getting more interesting.
As for the condition you mention, it’s quite a puzzle from an evo psych standpoint. I really don’t know the answer.
bbartlog
That is a pretty smart way to simplify the perception of a problem.
Rare genes + common environmental trigger = genetic.
Common genes + rare environmental trigger = environment.
My fitness reducing condition must have been too obvious, you guys both got it immediately. 8-)
My take:
The 20% monozygotic twin concordence rate compared to the 2% rate in the general population suggests a possible genetic predisposition. However the fact that 80% of co twins don’t have this condition indicates strong environmental factors at work. 2% of the general population also sounds much too high to be the result of a genetic mutation. The 80% reduction in offspring leads me to believe natural selection would wipe out the genes involved over time unless they offered a massive fitness benefit in some indirect way.
My personal guess is 100 to 1 in favor of environmental disturbance in utero.
Looc: “Genetic or Environmental?”
Or stochastic. Chance events early in development might account for the phenotype difference in MZ twins. Different numbers of cells. Partial differentiation before the split. Different chemical gradients. Different access to nutrients in the womb.
Also, to the baby the womb is the environment but the womb depends on the mother’s genetics. If a mother’s immune system increasing attacks “male” proteins with each successive male pregnancy should that be considered environmental or should that be viewed as the genetics of the female immune system?
Looc: “2% of the general population also sounds much too high to be the result of a genetic mutation”
If a trait depends on one gene and that gene undergoes strong fitness-reducing mutations at a rate one in ten thousand generations then 2% would be very high. Selection would keep the non-fit allele frequency very low. (This assumes the “non-fit” allele really does reduce fitness. In the case of homosexuality the loss of male reproductive successive might be balanced by increased female reproductive success.)
However if the trait depends on 100 genes, each accruing mutations at that same rate, then the non-fit phenotype could appear much more frequently. The non-fit allele frequencies would still be very low but the non-fit trait could be relatively common.
Fly
Dang! I am not as clever as I thought, you guys all knew the condition.
If a mother’s immune system increasing attacks “male” proteins with each successive male pregnancy should that be considered environmental or should that be viewed as the genetics of the female immune system?
You make a good point. If it occurs in a healthy mom and child, you are right, that is quasi-genetic. If the fraternal birth order effect is the tipping point, for example it occurs in mothers with already heightened immune systems I’d call it environmental. Not every study finds this effect and its always small. It’s a good clue anyway.
However if the trait depends on 100 genes, each accruing mutations at that same rate, then the non-fit phenotype could appear much more frequently.
Identical twins share the same genes, no matter how many are involved. With only a 20% concordence rate doesn’t that imply major environmental input? Theoretically it could have almost nothing to do with genetics and be the result of a disturbance in the womb. I have to imagine there are hundreds of allelles that either raise or lower the chances but so far none have been found.
stochastic
Wouldn’t that fall into the category of philosophy, not science? A stochastic trigger could never be proven nor disproven. If a theory can’t be falsified (is that the right word?) it exists outside the realm of rational inquiry.
Looc: “A stochastic trigger could never be proven nor disproven. If a theory can’t be falsified (is that the right word?) it exists outside the realm of rational inquiry.”
If a stochastic process is responsible for significant variation then it would be irrational to ignore the stochastic contribution.
Genetically identical flatworms raised in the same environment show significant variance in lifespan. Models that only look at genetic or environmental differences won’t accurately model flatworm aging.
Phenotype variation due to stochastic development is the source of a calico cat’s coloring. Stochastic gene silencing in cell lines during development leads to different skin patches expressing different pigment genes. So in this example backtracking from skin coloring to cell line differences showed a stochastic cause.
How could a stochastic contribution be shown? Suppose that when a scientist clones a homosexual mouse and implants the embryos in genetically identical mothers that 20% of the offspring are homosexual and 80% are heterosexual. The scientist could then look for brain structural differences that underlie the behavioral difference. He might then trace back the developmental differences that led to different brain structures. Ultimately the cell line differences might be tracked back to a stochastically dependent development pathway.
Clearly genetic and environmental differences cause phenotype differences, but I don’t think stochastic processes should be ignored.
The importance of stochastic processes is probably most obvious when modeling cancer cell evolution in tumors.
Fly
Right on! I’ve already read the article on the new thread. I’ll go there.