FOXP2 Gene: Speech and Language

FOXP2 Gene: Speech and Language

3 Types of Controls

Second:

Background Info

Difficulties:

• Used genomic sequence data produced from 38,000 year old Neanderthal (from Vindija Cave Croatia)
• Identify 7 sequence positions from autosomes and X chromosome

Why is this significant?

3 Types of Controls

• ancient remains contain low quantities of endogenous DNA
• modern human DNA = contaminant of ancient remains
• most human DNA sequences cannot be distinguished from Neanderthal sequences

Introduction

Third:

• One way to understand origin and evolution of language is to study evolution of genes for language acquisition

Phylogeny Tree

• Y Chromosome phylogeny
• expect Neanderthal Y chromosomes to be different than modern human Y chromosome
• unless male gene flow from modern humans into Neanderthals

3 Types of Controls

First:

• analyzed ratio of Neanderthal to modern human mitochondrial (mt) DNA in a segment
• Neanderthals and human DNA sequence can be differentiated based on base substitution

Negative

Control

• mock amplifications containing no template DNA

Introduction

• 44 extracts from 22 Neanderthal bones
• 2 bones with mtDNA abundant enough for PCR
• Both bones from North of Spain (El Sidron Cave)
• Bones were removed under sterile conditions
• Transported to extraction room

• Neanderthals = closest extinct relative of humans
• Share 2 evolutionary changes in FOXP2 gene with humans
• FOXP2 gene = gene for development in speech and language
• Inactivation of gene leads to abnormalities in orofacial movement and linguistic processing

Procedure

• Retrieve nuclear DNA sequences from ancient remains by PCR

Results

• Combined all control primers and ran a 2-step PCR
• 1st round: primers amplified 30 cycles
• remove portions of non-target
• 2nd round: amplify specific target individually

Objective

Autosomal Controls:

• 9/20 secondary PCRs yielded relevant products
• not all primer pairs yield products?
• Amounts are too little - amplification success by chance

Results

• Determine genotypes of Neanderthals at FOXP2 positions
• To retrieve direct genetic information from ancient remains to better understand recent human evolution
• Understand FOXP2 gene in Neanderthals and modern human language abilities

Overview

• Answer: Yes
• At 6 of 7 sites, products are same as derived alleles in humans
• At 1 site, first Neanderthal had derived allele, second had ancestral allele

• Humans have 2 nucleotide substitutions since our split from chimpanzee common ancestor
• Positions 911 and 977 in exon 7 of FOXP2 gene
• Caused amino acid substitutions
• 911: threonine to aspartic acid
• 977: arginine to serine

Procedure

Results

If one or both nucleotide substitutions in FOXP2 caused selective sweep in that genomic region then....

• Used samples from both Neanderthal
• PCR amplified Neanderthal introns upstream of exon 7 at 7 different sites
• Chose these sites b/c alleles at these sites are derived (mutated) in humans

Most likely substitutions and selective sweep occurred in the common ancestor of humans and Neanderthals, before divergence

Conclusion

More on

Selective Sweep

Objective

• Neanderthals carry FOXP2 protein/gene identical to humans in the two positions, different from chimpanzee
• The two nucleotide mutations (amino acid substitutions) were present in the common ancestor of humans and Neanderthals
• This research allowed us to hypothesize that possible language and speech abilities existed in Neanderthal
• Useful if one could sequence Neanderthal DNA for direct evidence to better understanding recent modern human evolution

Question:

Was the selective sweep around exon 7 of the FOXP2 gene of humans also present in Neanderthals?

Figure 1: A selective sweep

Under natural selection, a new beneficial mutation will rise in frequency (prevalence) in a population. A schematic shows polymorphisms along a chromosome, including the selected allele, before and after selection. Ancestral alleles are shown in grey and derived (non-ancestral) alleles are shown in blue. As a new positively-selected allele (red) rises to high frequency, nearby linked alleles on the chromosome ‘hitchhike’ along with it to high frequency, creating a ‘selective sweep.’

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By: Gigi (Beng Ci) Liang & Hody Yeung

From: The Derived FOXP2 Variant of Modern Humans Was Shared with Neanderthal