Genes and evolution I

Genes and evolution I

1. describe the theory of the molecular clock and its use in understanding human evolution

   • tree of evolution those that look the similar have the same ancestor
     • number of changes in an individual relates to how far back they are ancestors
   • molecular clock
     • base pairs mutate generation to generation
     • DNA differences reflect evolutionary history
   • ape DNA tree
     • common ancestor
     • human and chimp variation
       • variation in chimps greater than humans = even though there is less chimps

2. explain why immunity and sex genes are the fastest evolving genes in humans

   • humans expanded over short period of time
   • changing base pair/ amino acid
   • synonymous =change
   • protamine -1 (PRM1)
     • evolved to be the most different
     • protamine -1 subsitutes for histones in sperm and probably involved in sperm competition - toxic to each other

3. describe what is meant by copy number variation and its role in human adapatation

   • gene copy number variation
     • the globin gene evolved by gene duplication and mutation
     • more variation than people - copy power gens in multiple copies
     • population specific
   • population clustering of CNVs
     • 3 major blocks population specific
     • clustering of CNVs from 210 unrelated individuals. If CNVs were population specific they would appear at an apex
   • AMY1
     • the most common human gene copy number polymorphism reflects differing numbers of tandem repeats in the AMY1 gene
     • AMY1 maps to the short arm of chromosome 1
     • Always maps to single site , implying tandem duplications
     • sequence difference is small
   • AMY1 gene copy number in high starch populations has more copies

4. explain why some humans have partial or complete resistance to HIV

   • Route of HIV infection
     • CCR5 is a G-protein coupled receptor that normally controls migration of white blood cells from the blood to inflamed tissue
     • CD4 is a receptor on T-cells. HIV entry requires CD4 and CCR5. Some chemokines, such as RANTES, block HIV entry
   • variation
     • CCR5 receptor
       • The CCR5D32 allele carries a 32bp deletion leading to production of a non-functional CCR5 protein
       • CCR5D32 confers HIV resistance
       • No CCR5 - no infection
       • other mutant CCR5 alleles have partial function an partial resistance
       • CCR5D32 few % in north Europe. CCR5D32 not in other populations
     • at ligand genes
       • CCL3L1 shows strong binding to CCR5
       • CCL3L1 down regulates CCR5 by binging to and internalising it
       • variation in CCL3L1 gene copies from 0 to 11 per chromosome
       • more CCL3L1 - less infection
   • west nile virus infection
     • west nile needs CCR5 receptor function to encourage migration of white blood cells from the blood to inflamed brain tissues. So CCR5 null mutants have lower survival rate