W3L2 Paralogs, Orthologs and The McDonald Kreitman Test of neutrality

Question 1

Different between human and chimp genetic

Answer 1

-1% diverged in alignable region (60k aa)

Question 2

Further comparison between human and chimp genome

Answer 2

dN/dS comparisons between humans and chimps at different level
*Individual genes
*Genes grouped into “biological processes”
*Genes grouped by the tissue they are most abundant in

Question 3

Result of further analysis

Answer 3

-out of 17k gene, only 8 k useable in test
Average dN: 0.0026 per site
Average dS: 0.0033 per site some level of purifying selection
733/8079 had dN/dS greater than 1
33 significantly greater than 1

Question 4

Kosiol branch model selection

Answer 4

• Look for branches on a phylogenetic tree that show elevated dN relative to dS. Indicating a higher level of purifying selection

Question 5

Adaptation in mammal: virus is the main driver

Answer 5

• Viral Interacting Proteins have twice as many adaptive amino acid changes than do proteins that don’t interact with viruses.
• Estimate that Viruses have driven 30% of all adaptive changes in that part of the proteome that is conserved among mammals

Question 6

Site model

Answer 6

Looks for codons (triplets) within a protein that show elevated dN relative to dS across many sequences in an alignment.
* Detects “episodic evolution” where the same codons are repeatedly changing over evolutionary time

Question 7

Red queen hyphothesis dN/dS >1

Answer 7

• Co-evolutionary arms race
• The Pathogen evolves to avoid the immune system of the host.
• The hosts immune system evolves to identify the pathogen

Question 8

Problem with dN/dS

Answer 8

-only compare one genome of each species (no within variation)
-Nielsen study pool gene into classes
-compare 1:1 orthogonal
-dnds screen only pick up selection that favor losts of amino acid changes over silent changes
-not all adaptive change is shown by aa

Question 9

McDonald Kreitman Test

Answer 9

Compare pattern of nucleotide variation Within species and compare it to variation between species

Question 10

Equation for McDonald kreitman test

Answer 10

Question 11

Chi square test for McDonald Kreitman

Answer 11

Need to create marginals value for expected