L16: Comparative Genomics Flashcards
What is Francis Crick central dogma of molecular biology?
DNA is converted to RNA which produces protein
How big is the human genome?
3x10^9 base pairs
What is the mutation rate of human genome?
~10^(-8) base pairs / generation
10-100 new mutations/generation
Which selection increases fitness?
Positive selection causes mutation to spread through the population
Which selection reduces fitness?
negative selection will tend to remove the mutaiton form population
What is the most recent hypothesis that makes us human?
Human DNA has udnergone accelerated evolution since divergence from common ancestor with our closest primate relative (the chimpanzee)
What is the proof that humans underwent accelerated human evolution?
- Rats and mice diverged 3x as long ago as humans and chimps
- arguably rats and mice are far more similar than humans and chimps
What is comparative genomics?
comparison between mouse, chimpanzee, and human genome DNA sequence allows us to identify sequences that have undergone accelerated evolution in the human lineage
Which parts of comparative anatomy shows evolution of human skeleton comapred to chimp?
- limb evolution
- brain evolution
how much of the genomic DNA sequence do humans and chimps share?
- Humans and chimpanzees share ~99% genomic DNA sequence conservation
- 1% makes around 30 million bases
- some of these will likely be functionally important in driving human/chimp divergence
What are Human Accelerated Regions of DNA sequence?
HARs are DNA sequence conserved throughout mammal evolution then rapidly changed when humans evolved
What are the possible DNA sequencing techniques?
- Sanger DNA sequencing
- Next generation sequencing (NGS)
How are HARs identified?
for example:
- mouse, chimp and human genomic DNA is acquired through NGS
- comparative genomics studies identifying HARs, three main types of sequences identified:
- conserved between human and non-humans - likely to be functionally important and subject to positive selection but not to account for human specific phenotype
- conserved in non-human mammals and changed in humans –> HAR - strong candidates for being functionally important AND altered function positively selected during human evolution
- not conserved between human and non-humans - more likely to be silent mutations
What are the DNA functions?
- DNA sequence regulating gene expression: enhancers and promoters regulate gene transcritpion to messenger RNA (mRNA); tend to be located in non-coding DNA (ie introns or intergenic DNA)
- DNA sequence transcribed into RNA: protein coding messenger RNA [mRNA] exons translated to PROTEIN; non protein coding RNA (micro RNA [miRNA], long non-coding RNA [IncRNA], pseudogene RNA)
How do HARs map within genomic location?
vast majority of HARs:
- do NOT map to protein coding regions (mRNA/exons)
- do NOT map to non-coding RNA
- DO map to intergenic/intron regions where Promoters/enhancers tend to be found