2/3 - Origins of Genes and Genomes Flashcards
What is comparative biology?
Comparing and contrasting the properties of living beings to infer what the biology of the Last Universal Common Ancestor (LUCA) might have been like.
What are chemical fossils?
Chemical signals in rocks or other formations which serve as biomarkers for life
What are feasibility experiments in comparative biology?
Doing an experiment in the lab to test the feasibility of a hypothesis, this has low ecological validity.
Testing hypothesis about the origin of life.
Eg. Miller-Urey’s experiment where they mixed water, methane, ammonia, hydrogen and electricity to form amino acids. This triggered a whole discipline of study (prebiotic chemistry)
What is the RNA world?
For all ‘organisms,’ genetic information resided in the sequence of RNA molecules and the phenotype derived from the catalytic properties of RNA.
Which came first, nucleic acids or proteins? That is, if nucleic acids are needed to make proteins, and proteins are needed to synthesize nucleic acids, how could either have arisen?
Perhaps nucleic acids were initially both the storer of information and the replication machinery (both the chicken AND the egg).
What is the evidence for RNA being the first nucleic acid and the ‘chicken and the egg simultaneously?’
- DNA is modified RNA (not vice versa)
- 2’ OH on ribose makes RNA inherently less stable than DNA when single-stranded (double-stranged RNA looks like A-DNA, not the more common B-DNA)
- Both DNA and RNA can be used as information storage molecules (DNA is better, but can’t self replicate)
- 2’ OH makes RNA more reactive than DNA and capable of more complex secondary structures, with alternating single and double stranded regions
- Organisms synthesize RNA first
- Viruses use RNA as a storage info molecule
What are RNA molecules that can ‘do things’ on their own?
Ribozymes (enzyme + ribonucleotides)! These are naturally occurring RNA molecules capable of catalyzing chemical reactions on their own in the absence of proteins
Describe ribozymes
- Often under 100 nt in length
- Complex secondary structure, often hairpin shaped active sites (hammerheads) that allow them to cleave nucleic acids in a sequence-specific fashion
Eg. Groups I and II introns, hammerhead ribozymes (Virus like RNAs in plants and other eukaryotes), RNaseP (found in all life, cleaves off extra components of tRNAs, rendering them functional)
How can ribozymes be therapeutic?
Designer ribozymes can have therapeutic potential (eg. as digesters of viral RNA). In vitro evolution used to select for catalytic RNAs with desired properties.
- Introducing mutations allows you to evolve molecules to do very interesting things
True or false? The spliceosome is a ribozyme.
True, in almost all senses. It’s related to group II introns (autocatalytic RNA introns)
Spliceosomes are part of the SNRP complex and contains proteins. But URNAs derived from the spliceosome can perform a reaction that resembles splicing.
What is the general mechanism for the spliceosome?
There is a nucleophilic attack between a 2’ hydroxyl in the intron and the 3’ site of an exon. A lariat including the intron is released.
What are small nuclear RNAs (snRNAs)?
Probably derived from group II introns, there are spliceosomal.
There is high structural similarity between snRNAs and group II introns, especially since uRNA (uracil rich RNAs) came from autocatalytic spliceosomal uRNA.
What are group II introns?
- A type of self-splicing (catalytic) retroelement found in bacterial, mitochondrial and plastid genomes
- Can be mobile - they often possess a reverse transcriptase-encoding ORF in domain IV; the RT protein facilitates the movement of the intron to new locations in a genome
- Often the ORF in domain IV codes for a reverse transcriptase that facilitates the moving of mobile group II introns to other genes
Group II introns are ribozymes whose core splicing chemistry is identical to spliceosomal splicing.
Did the spliceosomal introns of nuclear genomes evolve from group II introns?
It seems so
- Some group II introns have become dependent on proteins for splicing
- Group II introns can fragment: the RNA domains of catalytically active group II introns can be synthesized by physically separated DNA fragments (exons can undergo ‘trans splicing’).
Is the ribosome a ribozyme?
Yes
Ribosomal proteins map to the outside of the structure. rRNA composes the bulk of it, as well as the entirety of the active site/peptidyltransferase centre)
The primitive ribosome could have been made entirely of RNA
