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What if everything that’s not a disease is polygenic?

In the early 2000s FOXP2 was dubbed the “language gene”. It was a sexy story. Humans exhibited accelerated adaptive evolution on this locus in relation to our relatives. Additionally, vocally oriented lineages such as birds and whales were also subject to the same process.

But over the past five years or so I’ve heard a lot of skepticism of the early claims as more genomic datasets have come online. Cell has a new paper which pretty much smashes the door down and breaks the skepticism out into the open, No Evidence for Recent Selection at FOXP2 among Diverse Human Populations:

FOXP2, initially identified for its role in human speech, contains two nonsynonymous substitutions derived in the human lineage. Evidence for a recent selective sweep in Homo sapiens, however, is at odds with the presence of these substitutions in archaic hominins. Here, we comprehensively reanalyze FOXP2 in hundreds of globally distributed genomes to test for recent selection. We do not find evidence of recent positive or balancing selection at FOXP2. Instead, the original signal appears to have been due to sample composition. Our tests do identify an intronic region that is enriched for highly conserved sites that are polymorphic among humans, compatible with a loss of function in humans. This region is lowly expressed in relevant tissue types that were tested via RNA-seq in human prefrontal cortex and RT-PCR in immortalized human brain cells. Our results represent a substantial revision to the adaptive history of FOXP2, a gene regarded as vital to human evolution.

Basically, our confidence in the inferences ran ahead of the data on hand. The reason that the story of the “language gene” spread like wildfire is that people wanted to believe. It was obvious that we were special. And we wanted to find how we were special.

In the 2000s, and even today, there was an idea that some single mutation might have allowed for the “Great Leap Forward” into behavioral modernity. I think that that model is probably wrong, and modern humanity was a more gradual and stepwise development. During the Eemian interglacial from 130 to 115 thousand years ago, agriculture did not emerge. No “lost civilizations” to our knowledge. Something happened to our species over the last 100,000 years. Probably biological, though in a way that facilitates cultural plasticity and evolution.

But genetically I bet it wasn’t that “one thing.” It was a lot of different things.

6 thoughts on “What if everything that’s not a disease is polygenic?

  1. The only thing to critizise about your comment is the title, because we find more and more diseases which are polygenic as well (as you know).

  2. Back to the old notion of bipedalism as the point of departure. Beyond that, Xeno’s paradox. Turtles all the way down.

    Sing, Thermodynamia, of time unspooling.

    Play, Sulla, upon the lute of eternal return.

  3. The interpretation of FOXP2 as a “language gene” never seemed justified, regardless of monogenicity/polygenicity considerations. The disorder can be characterized as articulatory, caused by lower facial rigidity. Since language is largely cognitive(as evidenced by non-oral applications in writing or sign language), there is no reason to regard FOXP2 as a likely gene for language.

    It is true that some members of the KE family are reported to have lower verbal IQ and impaired receptive language capabilities. This is often interpreted as evidence of the relevance of this single gene to language evolution. But if you look at studies of deaf children, they too have lower verbal IQs for example. Yet no one to my knowledge has called GJB2 35delG for example a “gene for language.”

  4. @poster
    yes, FOXP2 is rather a speech or vocalization gene then a language gene

    @razib
    archaic hominins could have had speech already
    the boom of sapiens in the last ~100k years could be due to something like lowered testosterone and more cooperative personality traits

  5. Some Diseases are monogenic.

    Many other dIseases are polygenic and miltifactorial.

    Everything other than diseases may be always polygenic and multifactorial. Multifactorial includes lifestyle and environmental factors. Even if it clusters with families, the heritability is unclear.

    Is this what is implied by the title?

    This is why I am a bit confused by educational achievement inheritance. That is both polygenic and multifactorial, and the conclusions regarding heritability may be preliminary.

  6. Is this what is implied by the title?

    yes.

    This is why I am a bit confused by educational achievement inheritance. That is both polygenic and multifactorial, and the conclusions regarding heritability may be preliminary.

    heritability is not a fixed statistic usually.

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