How similar is the DNA sequence?
> 98% identity
—> closest living relative to humans
Human and Chimp so similar, but why so different in phenotype?
Possible reasons:
genes specific to human / chimp
structural changes (e.g amino acid replacements)
gene regulatory changes
changes in few genes with large effects on phenotype
What is the nucleotide difference between human and Chimp?
How are they caused?
circa 1.23% (=35 million single nucleotide changes)
—> but some nucleotide variants are plymorphic —> difference circa 1%
caused by insertions or deletions of DNA bases (indels)
—> 5 million small indel differences —> counted: 5% difference between species
Which chromosome is the most divergent between human and chimp`?
And why?
Y chromosome
possible due to higher mutation rate in male germline (male reproductive cells undergo more cell divisions than female)
Which chromosomes are more or less divergent? Give the order.
Y chromosome spends all time in male
Autosome spends 1/2 of history in male
X chromosome spends 1/3 of history in male
Y > Autosomes > X
What does the presence of human-disease causing variants in the chimp genome suggests?
—> they are often fixed and ancestral
epistatic interactions between sites that leading to disease
compensatory mutations in chimp that render the mutations ‘harmless’ in chimp genetic backround
What is the largest gene family in mammals?
How many in human compared to other apes?
Olfactory receptor (OR) genes
—> involved in sense of smell
human: over 1000 OR genes (40% with intact ORF, 60% pseudogenes)
other apes: 70% have intact ORF (open reading frame)
—> OR genes being lost rapidly in humans
Why do humans have fewer OR genes?
hypothesis:
humans are only primates that eat cooked food
—> cooking leads to reduced need to identify toxins in food (denatured by cooking)
What is the Ka/Ks ratio?
or dN/dS
Ka = number of nonsynonymous differences per nonsynonymous site
Ks = number of synonymous differences per synonymous site
—> ALSO KNOWN AS dN/dS
What means Ka/Ks < 1
negative (purifying) selection
What means Ka/Ks = 1
no selection; completely neutral evolution
What means Ka/Ks > 1
positive selection
What types of genes show enrichment of positively selected genes?
tumor supression and apoptosis
spermatogenesis
sensory perception
immune defense
testes expressed genes
genes on X chromosome
Name some genes that play an important role in the phenotypic differentiation between human and chimp.
What causes mutations in these genes in humans?
FOXP2 - mutations causing problems with speech and language skills
microcephalin - mutations cause primary microcephaly (small brain, 1/4 of normal)
ASPM - mutations also cause primary microcephaly
What is suggested as major cause of phenotypic differnece between huamn and chimp?
And when was the large-scale comparison performed?
caused by differences in gene expression
—> When, where, and how much genes are expressed
in 2002
What was the main conclusion of the first large-scale comparison of human and chimp gene expresesion by Enard et. al?
2002
biggest gene expression difference occurs in brain
—> human brain transcriptome evolving faster than other tissues
What were the foundings of Khaitovitch et. al. in 2004 of comparing gene expression?
linear change in both brain and liver expression divergence with time —> no increase of expression changes in human brain
analogue to ‘molecular clock’ - expected under neutral evolution
How did Khaitovich explain the contradiction between their and Enards findings regarding gene expression divergence in human brain?
first study based on only 5% of brain-expressed genes
—> fewer genes on chips
—> results based only on genes with expression differences
What did Khaitovich find in further results?
2005
genes expressed in brain evolve slowest at both expression and protein levels
genes expressed in testis evolve fastest
2006
idea that natural selection favored gene expression in evolution of human brain —> higher linkage disequilibrium (LD)
What are metabolites?
small molecules of < 1500 Daltons, extracted from various tisseus
Are there many differences in the metabolite between human and chimp?
Yes! majority of changes occurring on human lineage
greatest changes occured in muscle, followed by brain
hypothesis: energy requirements of human brain led to reduction in energy consumption by muscles
—> explains why human larger brains with greater cognitive ability, weaker muscles than chimps/primates
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