Razib Khan One-stop-shopping for all of my content

June 29, 2017

Desperately seeking the secret of FOXP2

Filed under: FOXP2,Human Evolution — Razib Khan @ 6:04 pm

Since the early 2000s FOXP2 has shown up again and again in the press and scientific literature. Dubbed the “language gene” it exhibits evidence of accelerated evolution in the human lineage after it split from other apes. Additionally, a homolog of the same gene shows evidence of evolutionary change distinctive to songbirds and whales. Obviously this locus is involved in vocalization. Mutated mice on FOXP2 can even sing.

It isn’t difficult to connect the dots here. From 2002:

Dr. Paabo says this date fits with the theory advanced by Dr. Klein to account for the sudden appearance of novel behaviors 50,000 years ago, including art, ornamentation and long distance trade. Human remains from this period are physically indistinguishable from those of 100,000 years ago, leading Dr. Klein to propose that some genetically based cognitive change must have prompted the new behaviors. The only change of sufficient magnitude, in his view, is acquisition of language.

Klein’s thesis, advanced in The Dawn of Human Culture, is that a singular genetic change resulted in some sort of developmental cascade that allowed for the emergence of syntactically rich recursive language. And from language comes culture, and from culture comes world domination.

It was a clean and powerful hegemony while it lasted, but genomic and archaeological findings of the last decade have put such a elegant and simple model under a harsh light. With genomic technology even FOXP2 turns out to be much more complex and rich than the earlier reports had suggested. Neanderthals exhibited all the same mutations as modern humans to make them distinctive from chimpanzees. In other words, the changes on FOXP2 by and large predate the emergence of modern humanity, and go back closer to the root of the hominin lineage (Neanderthals and modern humans diverged ~600,000 years ago).

But FOXP2 keeps coming back. Why? It is an important gene. But another issue is that researchers still perceive in it the key to the holy grail of finding out what makes us distinctively human.

A new preprint (which is somewhat peculiarly formatted), takes another look at FOXP2, Human-specific changes in two functional enhancers of FOXP2:

Two functional enhancers of FOXP2, a gene important for language development and evolution, exhibit several human-specific changes compared to extinct hominins that are located within the binding site for different transcription factors. Specifically, Neanderthals and Denisovans bear the ancestral allele in one position within the binding site for SMARCC1, involved in brain development and vitamin D metabolism. This change might have resulted in a different pattern of FOXP2 expression in our species compared to extinct hominins.

The big picture is now the authors are focusing on gene expression levels as what might allow for modern human traits to be distinctive. Basically the DNA does not magically turn into protein. Biological machinery has to transcribe the sequence, and to transcribe it it has to bind to a particular region, a transcription factor binding site.

Most of the analysis involves comparing genomes of Neanderthals, Denisovans, and the human reference. I would be curious if they looked across lots of whole genomes to check if there was polymorphism in modern human populations. If modern humans with Neanderthal and Denisovan mutations had perfectly fine speech, that would be interesting.

Also, they spend a lot of time talking about how other genes interact and express with FOXP2, and all the other functions that are implicated. This is important, because of course selection may have nothing to do with speech, though perhaps speech changes are a side effect? Remember to that the Altai Neanderthal had some modern human admixture, and that one of the introgressed regions turns out to be FOXP2.

This sort of comparative genomic style research is interesting and suggestive. But we need more population wide analysis.

But, the authors do allude other work using genetic engineering where cell lines did show radically difference gene expression based on the mutation above. I do believe that CRISPR/Cas9 technology is cheap enough and going to be widespread enough that someone’s going to play around with splicing in “human” variants into primate models. Meanwhile, bioethicists will furrowing their brows about sequencing humans….

November 11, 2009

FOXP2 in Nature

Filed under: FOXP2,Human Evolution,Language — Razib @ 2:08 pm

Human-specific transcriptional regulation of CNS development genes by FOXP2:

…It has been proposed that the amino acid composition in the human variant of FOXP2 has undergone accelerated evolution, and this two-amino-acid change occurred around the time of language emergence in humans…However, this remains controversial, and whether the acquisition of these amino acids in human FOXP2 has any functional consequence in human neurons remains untested. Here we demonstrate that these two human-specific amino acids alter FOXP2 function by conferring differential transcriptional regulation in vitro. We extend these observations in vivo to human and chimpanzee brain, and use network analysis to identify novel relationships among the differentially expressed genes. These data provide experimental support for the functional relevance of changes in FOXP2 that occur on the human lineage, highlighting specific pathways with direct consequences for human brain development and disease in the central nervous system (CNS). Because FOXP2 has an important role in speech and language in humans, the identified targets may have a critical function in the development and evolution of language circuitry in humans.

Ed Young has a long entry on this paper, along with context.

Update: Someone on Twitter is suggesting we create a transgenic. Which direction?

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