Genetics - genetics underpinning human brain evolution
Study these flashcardsFree · spaced repetition · iPhone, Android, Mac & web
All cards
1
3 examples of human evolution where genetics is poorly understood
Bipedalism
Loss of body hair
Cranial morphology
Loss of body hair
Cranial morphology
2
4 features that make human brain function unique
General cognitive ability
Behavioural flexibility
Social intelligence
Language
Behavioural flexibility
Social intelligence
Language
3
What can be said about human brain size?
Big brain in proportion to body mass
Implies selection during human evolution for development of brain tissue
Implies selection during human evolution for development of brain tissue
4
How can more brain cells be produced?
More neuronal precursor cells
More mitosis, producing new cells
More mitosis, producing new cells
5
Describe microcephaly
Small brain
Mild cognitive impairment
Result of loss of activity of ASPM and MCPH1 gene
These genes seem to have an effect on overall brain size but little impact on brain function
Mild cognitive impairment
Result of loss of activity of ASPM and MCPH1 gene
These genes seem to have an effect on overall brain size but little impact on brain function
6
What can impairment of MCPH1 function lead to?
Insufficient production of nurons due to premature differentiation of neual stem cells and reduction of self-renewal divisions
Results in microcephaly
Results in microcephaly
7
What has NOTCH2 been found to be involved in?
Embryonic development
Humans/Neanderthals/Denisovans have duplications in this gene
Humans/Neanderthals/Denisovans have duplications in this gene
8
What has NOTCH2NL been found to be involved in?
Homo specific
Amplifies Notch signalling
Leads to increased proliferation of neural stem cells and delayed neural maturation
Amplifies Notch signalling
Leads to increased proliferation of neural stem cells and delayed neural maturation
9
1q21.1 deletion in NOTCH2NL =
Microcephaly
10
1q21.1 duplication in NOTCH2NL =
Macrocephaly
11
What has DUF1220 found to be involved in?
Associated with brain size and several mental health disorders
Fewer copies = SCZ
More copies = autism
Copies: Neanderthals > humans > other apes
Lengthens developmental period
Increases neual stem cells
Fewer copies = neurons mature faster and divide less
Fewer copies = SCZ
More copies = autism
Copies: Neanderthals > humans > other apes
Lengthens developmental period
Increases neual stem cells
Fewer copies = neurons mature faster and divide less
12
How might DUF1220 and NOTCHNL genes be related?
These genes may have co-evolved
13
Descrive the morphology of the human cranium
Globular
Strong left-right symmetry
Strong left-right symmetry
14
What did Heide find and when?
2020
Human specific gene ARHGAP11B edited into marmoset foetuses = larger neocortex with more gyri
Appears soon after LCA with Pan
Then there was another mutation, leading to the human specific form
Human specific gene ARHGAP11B edited into marmoset foetuses = larger neocortex with more gyri
Appears soon after LCA with Pan
Then there was another mutation, leading to the human specific form
15
What did Liu et al find and when?
2012
Peak expression of synaptic genes in PFC at 5y for humans (compared to before 1y in chimps)
Many genes expressed later in human brain > chimps
Only specific to PFC
Peak expression of synaptic genes in PFC at 5y for humans (compared to before 1y in chimps)
Many genes expressed later in human brain > chimps
Only specific to PFC
16
Which genes are human ancestor quickly evolved regions mostly found?
Within genes involved in regulation of gene expression in brain and gastrointestinal tract
17
Define enhancer
Distal genetic elements
Bind to transcription factos, promoting transcription of that gene
Not found next to the gene (not the same as a promoter region)
Bind to transcription factos, promoting transcription of that gene
Not found next to the gene (not the same as a promoter region)
18
What did Mangan find and when?
2022
Human ancestor quickly evolved regions are highly divergent from human-chimp ancestor
Evolved under increased mutation rates and positive selection
Diverged to produce hominin-unique enhancers to developing cerebral cortex
Human ancestor quickly evolved regions are highly divergent from human-chimp ancestor
Evolved under increased mutation rates and positive selection
Diverged to produce hominin-unique enhancers to developing cerebral cortex
19
Define cis-regulatory effects
On the same chromosome
20
Outline 2 pieces of evidence for human specific regulation of genes compared to Neanderthals
1/4 Neanderthal-introgressed haplotypes show cis-regulatory effects
N alleles downregulated in genes expressed in brain and testes
N alleles downregulated in genes expressed in brain and testes
21
What might have contributed to humans having more dendritic spines than any other primates?
Ancestral SRGAP2A stimulates maturation of dendritic spines
Human only SRGAP2C promotes increased no. of immature spines in humans
Human only SRGAP2C promotes increased no. of immature spines in humans
22
Define synaptic pruning
2 directions - deterioration of old connections and formation of new connections
Involved in learning and memory
Involved in learning and memory
23
How does the FOXP2 gene differ between chimps and modern humans
Only 2 aa differences between them!
24
Describe the difference in brain activity between ppl with normal FOXP2 and those with mutated variant
Normal = language areas active (eg. Broca's area) during speech
Mutated = activity all over brain, including right hemisphere
Mutated = activity all over brain, including right hemisphere
25
How does the human FOXP2 gene affect a mouse brain?
Affects dopamine levels, dendrite morphology, gene expression and synaptic plasticity of medium spiny neurons
Might impact cortical basal ganglia circuits relevant for speech and language
Might impact cortical basal ganglia circuits relevant for speech and language
26
What happens when mice lose the function of FOXP2?
Heterozygous knockouts = abnormal courtship song
27
FOXP2 functions
Regulatory gene - regulates hundreds of other genes
Expression is essential for language production
Expression is essential for language production
28
Outline evidence for H. sapiens specific FOXP2 variant
There is none!
29
Give another example of a gene potentially involved in language (other than FOXP2)
SLI1 and SLI2
Impairment = related to child's abilitly to produce nonsense word
Impairment = related to child's abilitly to produce nonsense word
30
Why is the evolution of SCZ not well understood?
High heritability
Reduced fertility
Why has negative selection not eliminated SCZ related alleles?
Could be that only a combination of particular alleles results in SCZ
Reduced fertility
Why has negative selection not eliminated SCZ related alleles?
Could be that only a combination of particular alleles results in SCZ
31
What did Gregory find and when?
2021
Pps with SCZ had fewer N derived genetic variation than controls
In unmedicated patients, more N admixture predicted less severe positive symptoms
In healthy pps, N introgression was associated with lower dopamine (increased dopamine associated with psychosis)
Pps with SCZ had fewer N derived genetic variation than controls
In unmedicated patients, more N admixture predicted less severe positive symptoms
In healthy pps, N introgression was associated with lower dopamine (increased dopamine associated with psychosis)
32
How might studying brain organoids help with our understanding of human brains?
Has potential to study complex gene networks
33
What did Somel find and when?
2013
Likely that many genetic variants associated with single traits and many genetic variants impact multiple traits
Likely that many genetic variants associated with single traits and many genetic variants impact multiple traits
34
6 methods that might be used to try and find human-specific changes
Using outgroups (primates, extinct hominins)
Examine sites of human specific changes (chromosomal changes, mutations)
Identify genes and gene families showing human-specific rapid evolution
Looking for human-specific gene expression differences
Target candidate genes from comparative studies/naturally occurring human mutations or from sequence data
Systems approach to promising gene groups
Examine sites of human specific changes (chromosomal changes, mutations)
Identify genes and gene families showing human-specific rapid evolution
Looking for human-specific gene expression differences
Target candidate genes from comparative studies/naturally occurring human mutations or from sequence data
Systems approach to promising gene groups
35
What has overarching delayed gene expression led to?
Neoteny
Delayed brain maturation
Delayed brain maturation
36
What is one of the major sources of evolutionary change?
Changes to gene expression via changes in regulatory sequences
37
Name one of the potential costs as a result of producing the human brain
Vulnerabilitly to psychapologies
Eg. SCZ
Eg. SCZ