Dynamic genomes, comparative genetics and human evolution

Question 1

What is comparative genomics

Answer 1

comparing the human genome sequence with those of other species

• this helps us to see what makes us genetically different but also understand what our genes do

Question 2

What is the endosymbiotic theory

Answer 2

i. eukaryotic cell with a nucleus
ii. engulfs a pre-chloroplast bacterium
iii. incorporation into host cell
iv. transfer of genes into nucleus

Question 3

How did comparative genomics confirm the endosymbiotic theory

Answer 3

found chloroplast DNA is most closely related to DNA from prokaryotic cyanobacteria. 4300 genes from Arabidopsis thouiona have prokaryotic origin. 3000 of these are no longer required but have other functions, 1300 genes are required for the chloroplast and transferred to plant genome and 87 genes were retained in the chloroplast genome

Question 4

What is synteny and why is it useful

Answer 4

synteny is the conservation of gene order
- segments are translocated, but large segments of DNA are conserved and gene order is the same

-synteny can reveal the evolution of gene sequences in related species
- synteny can identify duplicated or deleted genes and can identify genes of related function in different species

Question 5

How are comparative genomics used in human disease

Answer 5

dogs and drosophila are model organisms
- 60% of genes mutated in nearly 300 human diseases are found in drosophila including genes for prostate, colon and pancreatic cancer, cardiovascular disease, cystic fibrosis, Parkinsons and dementia. we can then study these genes in flies and understand potential cause
- molecular causes of 60% inherited diseases in dogs are caused at same or similar point where mutations are in humans

Question 6

How does looking at yeast help with human disease

Answer 6

• equivalent yeast genes to human disease genes have been identified and characterised, this has helped determine the function of the gene through experiments in yeast
• eg. colon cancer genes in humans are the same as MSH2 and MLH1 in yeast. In yeast these genes are responsible for DNA repair

Question 7

What is the olfactory receptor family

Answer 7

• represents 3% of total number of genes
• each receptor identifies a different odour
• a different odorant or odour molecule is identified by one receptor which is encoded by its own gene
• there are 906 gene sequences which code for olfactory receptors which bind to over 10000 odour molecules
• there are seven transmembrane G protein-coupled offactory receptors
• each receptor sub type is responsible for a small number of different odours
  -a combinational code for olfaction
• there are missense olfactory receptor alleles and variation of over 30% for odourant receptor cells

Question 8

Olfactory receptor genes in vertebrates

Answer 8

• size of the gene family is much larger in vertebrates than other species such as yeast
• 80% of human olfactory genes occur in clusters
• evolution of the gene family has occurred rapidly in vertebrates

Question 9

What is gene duplication

Answer 9

subfunctionalisation: duplicated genes perform different aspects of original gene function

neofunctionalisation: where one of the duplicated genes acquires a new function

pseudogene (disappears)
- an inactive and non-functional gene

• homologous genes share a common ancestor
• orthologous genes are homologous genes located in genomes of different organisms
• paralogous genes are two or more homologous genes located in the same gene

Question 10

Modern humans bred with Neanderthals and Denisovans

Answer 10

Neanderthals
- genome 99.84% identical to human genome
- between 1-4% of non-African genome from Neanderthals
- about 1/3 of Neanderthals genome is seen in genome of non-African humans

Denisovans
- Denisovans contribute around 1-6% of genome in present day Meronesians
- EPASI gene shown to confer adaptation to high altitudes inherited from Denisovans