Lecture 23 (what does the genome tell us about being human?) Flashcards
Comparative genomics
Compares the genomes of different organisms to answer questions about genetics and other aspects of biology.
Used to discover what is common and what is different. Things in common are called ‘conserved’ and may encode biology in common between species (common genes). Things that are different may encode organism specific biology. So by comparing genomes you learn a little about which parts of the genome do what.
How do you compare sequences?
By lining them (bases/ genomes) up next to each other and making each point where sequences are the same, this is a process called aligning
Aligning in genetics
a way of arranging the sequences of DNA, RNA, or protein to identify regions of similarity that may be a consequence of functional, structural, or evolutionary relationships between the sequences.
Why do we compare genomes within a species?
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 (therefore there is more and more understanding)
We can now sequence the human genome for $4000 (it is getting cheaper and cheaper to do)
Why compare genomes between species?
What could we learn about an organism if we compare its genome with others?
- What sort of genes they have
- How difference between species arise
- Relationships between species
What would happen if we did this with humans?
What does our genome tell us about being human?
Can we use the human genome to work out which bits of our DNA encode for tool use and language? (we are one of the few species that use tools and they have made our cultures and society what it is) (communication allows us to transmit information to other effectively)
By comparing our genome with animals that don’t do things that we do might find where our genome differ - potentially the bits of DNA encoding our different biology
This is hard because … There are lots of differences(genomes are very large, majority of it doe not encode for proteins, so there are lots of changes in the genome of humans and it is hard to know what changes have given rise to new traits), we share many of our genes with other animals (there are no human specific genes, especially for tool use and language specifically) and we dont really know what most genes do (in different species, the same gene can do different things)
How to compare genomes of closer relatives/extinct relatives?
DNA from dead things can remain in the environment (therefore DNA can be sequenced from dead things)
DNA degrades and is masked more by modern DNA
DNA bases are also modified as they degrade, sometimes changing the sequence
Ancient DNA can be extracted and identified in very special circumstances
It has been used to determine the relationships of extinct animals like moas and mammoths
Could it be used to sequence an extinct human genome?
Neandethals are probably
the closest relatives to modern humans
What have they got from neanderthals DNA sequencing?
4 billion neanderthal nucleotides
Identified and discount modern contamination
Gathered sequence from 3 individuals probably (2 individuals are very closely related so it could just be two individuals total)
Gathered enough sequence to compare with modern human genome sequences from around the world
Identified bits of DNA that differ between neanderthals and us
Most amazing findings from looking at neanderthal DNA?
That some of us carry neanderthal DNA
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
Mixing of our family trees
Some neanderthals and homo sapiens interbred
Yoruba and san show no signs of neanderthal DNA (suggests no neanderthal and homo sapien interbreeding here)
So some of us carry neanderthal DNA…explain
This does not mean that those of us with neanderthal DNA have a different set of genes. It just means that our DNA holds variants that arose in Neanderthals. (evolved in neanderthals and transferred to us through interbreeding)
2-4% of the genome of non-africans is made up of variants that arose in neanderthals
So Neanderthal DNA adds to the variation in our genome that might be related to our phenotype
Denisovian findings
As well as neanderthal DNA….A finger bone was also found in Denisova, whose mitochondrial DNA does not match neanderthal or modern human DNA
The genome from this species of archaic human was sequenced from a tooth found in the same cave in 2010.
Denisovan variation is also found in the human genome, where it makes up 4-6% of the genomes of present-day melanesioans (homo sapiens mated with neanderthals, we mate with Denisovans and we therefore have them in our genomes)
Neanderthals, Denisovans and homo sapiens
Neanderthals and Denisovans seem to be more closely related than either are to humans
What does sequencing our genome tell us?
The sequencing of genomes has helped us better understand who we are and where we came from
The key technology here is being able to compare genomes
By comparing whole genomes from multiple species we can start to understand where our characteristics come from
This is the same approach used modern disease genetics - data rich and statistically intense analysis
Our extinct relatives are not just fossils in our museums, but live on as variants in our genomes which affect our biology
