Monday, September 16, 2024

How are We Evolving?

Ali Akbari et al on BioArxiv: 

We present a method for detecting evidence of natural selection in ancient DNA time-series data that leverages an opportunity not utilized in previous scans: testing for a consistent trend in allele frequency change over time. By applying this to 8433 West Eurasians who lived over the past 14000 years and 6510 contemporary people, we find an order of magnitude more genome-wide significant signals than previous studies: 347 independent loci with >99% probability of selection. Previous work showed that classic hard sweeps driving advantageous mutations to fixation have been rare over the broad span of human evolution, but in the last ten millennia, many hundreds of alleles have been affected by strong directional selection. 

This only confirms what people have thought from other evidence, that our evolution has speeded up rather than slowed down: In what directions have we been evolving?

Discoveries include an increase from ~0% to ~20% in 4000 years for the major risk factor for celiac disease at HLA-DQB1; a rise from ~0% to ~8% in 6000 years of blood type B; and fluctuating selection at the TYK2 tuberculosis risk allele rising from ~2% to ~9% from ~5500 to ~3000 years ago before dropping to ~3%. We identify instances of coordinated selection on alleles affecting the same trait, with the polygenic score today predictive of body fat percentage decreasing by around a standard deviation over ten millennia, consistent with the Thrifty Gene hypothesis that a genetic predisposition to store energy during food scarcity became disadvantageous after farming. We also identify selection for combinations of alleles that are today associated with lighter skin color, lower risk for schizophrenia and bipolar disease, slower health decline, and increased measures related to cognitive performance (scores on intelligence tests, household income, and years of schooling). These traits are measured in modern industrialized societies, so what phenotypes were adaptive in the past is unclear. We estimate selection coefficients at 9.9 million variants, enabling study of how Darwinian forces couple to allelic effects and shape the genetic architecture of complex traits. 

Lighter skin is a really obvious one; peope in the north need sunlight for vitamin D more than they need protection from the tropical sun. I just mentioned our declining ability to store fat, which is related to the spread of agriculture, and rising intelligence seems pretty useful. But some of these raise questions: if schizophrenia and bipolar disorder are being selected against, how did they ever become common in the first place? Why on earth would celiac disease rise in a region where wheat is the staple food?

They also find that the risk of Multiple Schlerosis is rising due to selection, which is really bizarre, but that male-pattern baldness is decreasing, raising again the question of how it ever got to be common.

Stay tuned to this; we are going to learn a lot more about genetics and how we are evolving over the next decade.

2 comments:

  1. This only confirms what people have thought from other evidence, that our evolution has speeded up rather than slowed down: In what directions have we been evolving?

    The fact that they're trying to compare ancient natural selection and modern unnatural selection is supremely frustrating.

    It's not so much that allele changes happened less frequently in the past - it's that when they happened, they were more frequently fatal, and thus didn't persist in the population.

    But some of these raise questions: if schizophrenia and bipolar disorder are being selected against, how did they ever become common in the first place? Why on earth would celiac disease rise in a region where wheat is the staple food?

    All they say is "lower risk" of schizophrenia and bipolar disorder. How much lower isn't specified. And just because one chance is lower than another one, doesn't mean both chances aren't still high enough to easily account for something happening with regularity.

    That said, we still don't actually know the causes of schizophrenia or bipolar disorder. It does seem they have particularly high rates of heritability, but they also crop up in people with no family history of them from time to time. And it's clear that they both involves more than just genetics, but also general health, mental health, environmental factors, etc.

    But ultimately, to answer your question about how a portion of population arises which suffers from these afflictions our genes are trending against them, well... it's a question of who survives to pass on their genes, and who doesn't.

    And we're talking about diseases that people didn't even have proper names for or conceptions of until a VERY short time ago. And we're also talking about diseases that usually don't show symptoms until later in life, well after most people afflicted have already passed on their genes.

    As for celiac disease, again, all that is necessary for something to arise in a population is for it to be survivable - at least until someone has offspring, anyway. No doubt lots of people in history suffered from gluten intolerance - but like with most modern sufferers, eating bread didn't kill them, it just caused inflammation and the related symptoms, and they suffered through it and carried on with life, complaining about their "bad digestions", but otherwise living normal lives.

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  2. Harpending and Cochran vindicated. Also Pfizzer.

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