Genet 302 lec 47 & 48
What is a transposable element?
A DNA sequence that can move to a new location in the genome
Who discovered transposable elements?
Barbara McClintock
Are transposable elements found only in eukaryotes?
No, they are found in both prokaryotes and eukaryotes
What unique thing does a TE usually encode for itself?
One TE-specific protein
Who does most of the other steps in TE mobilization?
Host-cell proteins
How do Class I transposable elements move?
By copy and paste
What intermediate is used by Class I TEs?
An RNA intermediate
What second intermediate is formed before insertion by Class I TEs?
A cDNA intermediate
What enzyme activity is needed to make the cDNA intermediate of a Class I TE?
Reverse transcriptase
How would you diagram Class I TE movement?
Original TE DNA → transcription → RNA intermediate → reverse transcription → cDNA → insertion at a new location while the original copy remains
What is the key result of Class I transposition?
The original TE stays and a new copy is added elsewhere
What human Class I TE example was emphasized?
Alu
How do Class II transposable elements move?
By cut and paste
What intermediate is moved by Class II TEs?
A DNA intermediate
How would you diagram Class II TE movement?
Original TE DNA → excision of TE DNA → movement of TE DNA → insertion at a new location
What is the key result of Class II transposition if the original gap is repaired by NHEJ?
The TE is gone from the original location
What repair pathway can restore a Class II TE at the original site after excision?
HDR
What is the key result of Class II transposition if the original gap is repaired by HDR?
The TE can still be present at the original location
How abundant are TEs in the human genome?
About 54%
Where are TEs commonly found in the human genome?
Between genes and in introns
Can some TE insertions be polymorphic in humans?
Yes
What does a polymorphic TE insertion mean?
Some people have the insertion and some do not
What is one major disadvantage of TEs in a genome?
They consume cellular resources
Why do TEs consume resources?
They require transcription, protein production, and DNA replication
How can TEs cause germline mutations by moving?
They can insert into or disrupt genes
Why is DNA methylation used against TEs?
To reduce TE mobilization and prevent mutation
How can TEs cause germline mutations without moving?
They provide repeated sequences that can promote NAHR
What is one beneficial way hosts use TEs?
Hosts recruit them for useful functions such as immune-system rearrangements and telomere biology
How can TEs facilitate evolution by altering mRNA splicing?
A TE insertion can create new splice patterns or new transcript forms
How can TEs facilitate evolution by altering gene expression?
They can bring or change regulatory sequences that affect transcription
What example of TE-altered gene expression was given in Drosophila?
TE-associated overproduction of antibacterial proteins
What happens to TE suppression systems in yeast under stressful conditions in this lecture?
They are turned off
Why might turning off TE suppression in stress be useful evolutionarily?
It increases genomic variation that may help adaptation
How can TEs help chromosome regulation by genome organization?
They can move enhancers away from promoters and move genes apart
Why can moving genes apart be beneficial?
It can prevent epigenetic marks from interfering with neighboring genes
List the main disadvantages of TEs in a genome
They use resources, can insert into genes, and can promote NAHR-based mutations
List the main advantages of TEs in a genome
They can be recruited for host functions and can facilitate evolution by changing splicing, gene expression, and genome organization
What problem do telomeres solve?
The end-replication problem of linear chromosomes
What is the end-replication problem?
Regular DNA polymerases cannot fully replicate the ends of linear chromosomes
Why is telomere DNA useful?
It acts as sacrificial DNA at chromosome ends so important genes are not lost first
What enzyme makes telomeres?
Telomerase
What is telomerase made of?
RNA and protein
What kind of enzyme is telomerase?
An RNA-dependent DNA polymerase
How does telomerase work in one sentence?
It uses its own RNA as a template to extend telomere DNA at the 3′ end
What telomere repeat is used in humans and mice?
TTAGGG
What are the three ways linear chromosomes maintain their ends in this lecture?
Telomerase, transposable-element systems, and ALT
What organisms in this lecture use TE-based chromosome-end maintenance?
Some plants such as onions and some animals such as Drosophila
How does the Drosophila TE system maintain chromosome ends?
Class I TEs transpose onto chromosome ends
What is ALT?
Alternative lengthening of telomeres
How does ALT maintain chromosome ends?
A short telomere uses telomere DNA from another chromosome as a template through DNA repair and DNA polymerases
What are the functions of telomeres?
They buffer chromosome ends from sequence loss and prevent chromosome ends from being mistaken for broken DNA
What happened in telomerase-knockout mice over generations?
More telomere loss, more aneuploidy, and more end-to-end chromosome fusions
Why do end-to-end chromosome fusions happen when telomeres are lost?
NHEJ treats chromosome ends without telomeres like DNA breaks and joins them
Which human cells normally have TERT on in this lecture?
Embryonic cells, germline cells, and some stem cells
What happens in most human somatic cells because TERT is off?
Telomeres shorten with division and cells eventually become senescent
Why are most human somatic cells mortal?
Without telomerase, repeated cell division shortens telomeres until checkpoints stop proliferation
Why do many cancer cells turn TERT on?
To maintain telomeres and become immortal
Why are telomerase inhibitors alone not ideal anticancer drugs in this lecture?
They can select for cancer cells that use ALT
What relationship between telomeres and aging was emphasized?
Older people tend to have shorter telomeres
Why do TERC or TERT mutations resemble premature aging disorders?
They impair telomerase function and accelerate telomere-related cell limits