Human vs Chimp

98%

Flys with a DNA seqeunce divergence of over 5%

• Are there genes specific to human or chimp that cause differences?

• Are structural changes (i.e. amino acid replacements) responsible for the difference?

• Are gene regulatory changes responsible for the difference?

• Do changes in a few genes have a large effect on phenotype?

1%

single nucelotide differences in aligend seq exluding gaps

5%

no

Y most, X the least

This may be due to a higher mutation rate in the male germline, because male reproductive cells undergo more cell divisions than female. The Y chromosome spends its entire evolutionary history in males. Autosomes spend 1/2 of their evolutionary history in males.

The X chromosome spends 1/3 of its evolutionary history in males. Thus, if there is a higher mutation rate in males, we would expect divergence to follow the pattern: Y > Autosomes >X.

• the average protein shows 2 amino acid differences

• 30% of all proteins are identical between the two species

there may be epistatic interactions between sites that lead to disease. There may be compensatory mutations in the chimp that render the mutations “harmless” in the chimp genetic background.

Olfactory receptors, involved in the sense of smell

• around 1000 OR genes in human

• only 40% intact ORF

• 60% pseudognes

other great apes have 70% ORF for OR genes

One hypothesis: humans are the only primates who consume cooked food. One might speculate that cooking leads to a reduced need to identify toxins in foods (since these are denatured by cooking).

However, some of the OR genes that remain in the human genome show evidence for positive selection. Thus, it appears that many unnecessary OR genes are lost and become pseudogenes, but others have evolved adaptively in humans.

• type of selection acting on a protein-encoding gene

• Ka = the number of nonsynonymous differences per nonsynonymous site

• Ks = the number of synonymous differences per synonymous site

Ka/Ks < 1: negative (purifying) selection

Ka/Ks = 1: no selection; completely neutral evolution

Ka/Ks > 1: positive selection

Note that Ka/Ks is sometimes known as dN/dS or ω

• tumor supression and apoptosis

• spermatogenesis

• sensory perception

• immune defense

• testes expressed genes

• genes on the X chromosome

mutations in this gene have impaired speech and language skills.

humans with mutations in this gene have primary microcephaly (small brain of ≈400 cm3). A normal human brain has a volume of ≈1,400 cm3

mutations in this gene also cause primary microcephaly in humans

It means the gene variant entered the modern human gene pool through interbreeding (hybridization) with an archaic, now-extinct human species (like Neanderthals) in the past, rather than arising from a recent mutation within modern humans.

Because humans and chimps are so similar in DNA and protein sequence, it has been suggested that many of the phenotypic differences between species may be caused by differences in gene expression. That is: when, where, and how much the genes are expressed.

• transcriptomes: 2 types microarrays

  • using blood, liver & brain from

  • humans, chimps, orangutans & macaques

• proteomes: 2D-PAGE

Microarray 1: Affymetrix human oligonucleotide GeneChips

• RNA was from from brain and liver of 3 humans, 3 chimps, and 1 orangutan

Microarray 2: cDNA microarrays

• used to compare blood, liver, and brain expression among humans, chimps, and rhesus macaques.

Result: the brain transcriptome appeared to evolve faster along the human lineage. This is consistent with the hypothesis that rapid evolution of the human brain was caused by changes in gene expression.

• found a large excess of “quantitative” changes in human brain, relative to “qualitative” changes

• This is also consistent with many changes in brain gene expression.

Conclusion: Biggest difference between human and chimp is gene expression in the brain.

Contradiction: Using larger arrays (28,000 cDNAs), they found a linear change in expression divergence over time in both the brain and liver, showing no special acceleration in the human brain.

Model: This linear change acts like a "molecular clock" of gene expression, meaning most transcriptome evolution follows a neutral model (random drift rather than active selection).

The first study suffered from a sampling bias:

1. It only analyzed about 5% of all brain-expressed genes (fewer genes on the early chips).

2. Its final statistical conclusions were flawed because they were based only on the pre-selected genes that already showed expression differences between humans and chimps.

Slowest: The Brain (it is under immense purifying selection; changing brain proteins or expression easily breaks vital systems).

Fastest: The Testis (driven by intense sperm competition and sexual selection).

When you map the few evolutionary changes that do happen onto specific lineages, there is a significant excess of changes purely on the branch leading to humans. This means human brain evolution experienced a unique shift away from the typical constraints seen in other primates.

The genomic regions surrounding these altered brain genes show higher Linkage Disequilibrium (LD) in humans. This is a classic signature of a "selective sweep", where positive selection rapidly drives a beneficial mutation to fixation, reducing genetic variation and dragging the surrounding DNA along with it.

The Finding: Metabolome changes on the human lineage occurred heavily in muscle, followed closely by the brain.

The Hypothesis: The massive energy demands of our expanding, highly cognitive human brain forced an evolutionary reduction in the energy consumption of our skeletal muscles. This explains why humans have exceptional cognitive abilities but are physically weaker than chimps and other primates.