Human vs Chimp

2005

human chimp: > 98% identifal

2 fruit fly species: <95% identical

-> possibilities to create differences in phenotype human/chimp:

- genes specific to human or chimp

- Are structural changes (i.e. amino acid replacements)

- Are gene regulatory changes

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

when looking at aligned sequences, no InDels

• Nucleotide divergence is 1.23% between 1 human and 1 chimp genome (≈35 million single nucleotide changes)

• However, this number is inflated because some nucleotide variants are polymorphic within humans or chimps.

  -> The estimated proportion of fixed differences is ≈1%

When including small InDels

• ≈5 million small (1–15 bp)

  -> divergence of 5%

in neither are structural variants included

divergence pattern: Y > autosomes > X

(males make more mistakes)

• 30% of proteins identical

• on average 2aa changed

• This suggests that 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 receptor (OR) genes: smell sense

• >1000 in human

• 40% functional (have intact ORF)

• 60% pseudogenes

in other apes, ~70% functional

-> LOST RAPIDLY in human

explaination: humans are the only primates who consume cooked food -> no need to smell toxins

BUT some show positive selection i.e have adapted for human

use ka/ks ratio, also known as dn/ds or omega

• 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

reminder: non-synonymous leads to difference in aa seq

compare all protein-encoding genes between human and chimp and look for those with Ka/Ks > 1

If an additional outgroup species is used, such as macaque or mouse, one can determine if selection occurred on the human lineage or on the chimp lineage. Some newer statistical methods can detect positive selection even when Ka/Ks < 1

no, due to multiple testing issue. Usefull for identifying functional gene groups under pos. selection though

• tumor supression and apoptosis

• spermatogenesis

• sensory perception

• immune defense

• testes expressed genes

• genes on the X chromosome

same groups show up across species (mouse-rat or D. melanogaster-D. simulans)

No, there is little evidence for positive selection on genes expressed specifically in brain

impaired speach and language skills

accelerated evolution (more amino acid changes) in lineages

leading to humans (on human branch)

-> natural selection may have favored ability to use language in humans

primary microcephaly = small brain of only 400cm instead of 1400cm

accelerated evolution (more amino acid changes) in lineages

leading to humans

-> natural selection may have favored larger brains

also causes primary microcephaly = small brain of only 400cm instead of 1400cm

accelerated evolution (more amino acid changes) in lineages

leading to humans

-> natural selection may have favored larger brains

• 2002

comparison of transcriptomes

• blood, liver, and brain

• from humans, chimps, orangutans, and macaques

• using two different types of microarrays

  Microarray 1: Affymetrix human oligonucleotide GeneChips (≈12,000 genes).

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

  • All RNA was extracted from dead males.

  • A similar experiment was performed using 3 mouse species of nearly equal divergence as the primate species and Affymetrix mouse chips.

  Microarray 2: cDNA microarrays (human unigene set, ≈18,000 genes) were used to compare

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

human and chimp proteomes

• using 2D-PAGE

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.

• 2D-PAGE comparison of proteomes 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.

But this study examined only a small, selected fraction of brain-expressed genes, so it may have overestimated the effect.

2002 study: It appeared that human brain gene expression changed unusually quickly. This suggested that changes in gene activity may have contributed to human brain evolution.

But this study examined only a small, selected fraction of brain-expressed genes, so it may have overestimated the effect.

2004 study: Using many more genes, researchers found that expression differences in brain and liver accumulated roughly steadily over time—a pattern consistent with mostly neutral evolution. They did not find that the human brain had an exceptionally high overall rate of expression change.

2005 study: When tissues were compared, brain-expressed genes changed more slowly than genes expressed in other tissues, especially testis (fastest). This suggests that brain genes are generally under strong purifying selection, because harmful changes in the brain are likely to be removed.

2006 study: This did not necessarily overturn the 2005 result. It asked where the changes occurred.

Even though the brain had fewer total changes than other tissues, more of those brain changes occurred on the human lineage than on the chimpanzee lineage.

The evidence does not show that the human brain simply evolved faster than every other tissue; instead, brain genes are generally highly conserved, but a subset of gene-expression changes may have occurred disproportionately—and possibly adaptively—during human evolution.

eg:

Brain: few changes overall Human lineage: 8 changes Chimp lineage: 2 changes Testis: many changes overall Human lineage: 50 changes Chimp lineage: 50 changes

• metabolites: small molecules of <1,500 Daltons

• many differences between human and chimp, majority of changes occurring on the human lineage

• greatest changes in muscle, followed by the brain

hypothesis: energy requirements of the human brain have led to a reduction in energy consumption by muscles