Lecture #30 - What can we learn from the human genome? Flashcards
Define Synteny
When genes are present in the same order on chromosomes of different species, indicating a common ancestry.
Define CNV
Copy number variant. Site in the genome at which individuals of the same species have different number of copies of a gene or genetic region.
Define InDel
Variation in genome arising from insertion or deletion of base pairs.
Define SNP
Pronounced “SNIP”, a single nucleotide polymorphism. Site at which individuals of the same species have a different base pair in their genome.
Memorise this - graph of how we share all genes
“Distribution of the homologs of the predicted human proteins”
No gene that’s “human only” or even “ape only”
Comparative Genome
- What?
- Discover what?
- And also discover?
- To discover what is in common and what is different (idea of comparing genomes and learning about em)
- Things in common are called ‘conserved’ and may encode biology in common between species so discover what’s common
- Discover which bits of the genome do what by comparing
How to compare sequences? What’s it called? What about genomes (3)
By lining them up next to each other and marking each point where the sequences are the same. Called aligning. Can find what’s common and what’s not.
- Aligning genomes is very hard because you don’t know where to start.
- Aligning genomes of closely related species is easier because there are fewer changes (less variation)
- Aligning coding sequences is much easier than non- coding sequences because they’re restricted to hpw proteins can be coded for (non coding are different)
Comparing genes - what useful things does it let you know?
Once you have predicted genes in a genome you can compare genes between species.
This let you know lots of useful things:
- Where genes come from.
- What sorts of likely gene function are encoded by a genome.
- How much genetic information do we share with our relatives.
Insect Genomes
Black line where genome common
Most species have conserved eve gene (it’s in the coding region)
Usually coding genes don’t change as much as non-coding
The convervation of genes:
When we compare genes, we discover that the……
…vast majority of genes in the human genome can also be found in other animals.
- Many are also found in yeast
- Many in bacteria
- We share many of our genes with all other animals.
What do we find if we compare genome sequences? (3)
- Gene sequences are conserved between animals
- Gene order and organisation is also often conserved - called synteny
- By comparing the order of genes on chromosomes in one species with another you can identify sytenic “blocks.”
What does synteny tell us? (3)
- Blocks of chromosomes are conserved through evolution.
- While chromosomal rearrangements happen, they don’t often get fixed in a population.
- Closely related species have very similar gene order and organisation.
We can also compare within species. By comparing genomes between indivisuals we can…(4)
- By comparing genomes between individuals we can find out where differences occur.
- Differences might be associated with
- disease
- characteristics of an individual
- Evolutionary history
- More and more human genomes are being sequenced or mapped.
- We can now sequence the human genome for US$4000
Not all genes are on/off - the regulation of genes is being acted on by evolution - this makes us different to chimps
- PCR is sensitive - elaborate
- Ancient DNA - 2 things
- PCR is so sensitive that it can pick up an amplify tiny bits of DNA. But contamination is a huge problem - can accidentally also amplify the genes of the person who handled it.
- DNA bases are modified as they degrade, sometimes changing the sequence. Ancient DNA can be used to determine the relationships of extinct animals, like moa and mammoths (they fell in cold ice caves so genes preserved well)
Who was the first person to extract DNA from an ancient specimen - a ____ year old ____ ____?
Savante Paabo
First person to extract DNA from an ancient specimen- a 4000 year old Egyptian mummy
Tell me about the Neanderthal
- Closest relative to human
- Lived 130k - 30k years ago in Europe and Asia
- Lived in cold caves so DNA preserved
- Dunno if spoke but structure of throat indicates something
- Made tools
- Made necklaces, did funerals etc so were somewhat sophisticated
- They’re our sister species
- Amplification of their DNA from middle of Nean bone (least contaminated part).
What it showed:
- 4 billion Neanderthal nucleotides
- Clever techniques to identify and discount modern contamination
- Sequence from 3 individuals (probably)
- Enough sequence to compare with modern human genome sequences from around the world
- Bits of DNA that differ between Neanderthals and us (ouch)
That’s amazing because:
- These comparisons show that some of us carry Neanderthal DNA.
- The data indicates that modern humans from europe and asia carry Neanderthal alleles.
- Those from Africa show no signs of these alleles.
- The most parsimonious explanation for this is that where modern humans met Neanderthals, they interbred.
What can’t we learn from the human genome sequence? (4)
- The sequence of the human genome, and that of other organisms is a huge achievement.
- It allows us to do experiments we could only have dreamed of before it was sequenced.
- It will stand as a vital part of biology for as long as Humans exist
- BUT, it doesn’t tell us the function of genes!
Basically, can’t predict anything but ancestory
So how do you find the function of genes?
You knock them out in an organism, and study the resulting phenotype.
For humans - hard to do bc ethics I guess so basically what we have so far is what we’ve researched on other species and assumed that what it does in a fruit fly will be the same as what it does in us.
Summary
- Having sequenced genomes we can compare them.
- When you compare genes, you find that many genes are shared between species.
- When you compare genome sequence you find that closely related species have high levels synteny.
- By comparing genomes, you can identify evolving sequences. Genomics doesn’t tell you the function of genes.
