Midterm 2 - Notes 3 (Part 2) Flashcards
What are modules?
Any functionally discrete portion of a locus
What are 3 examples of modules?
- Cis regulatory element
- Protein domain (exon)
- Alternative splice site
What does redundancy imply?
That both genes have the same function
- cant be maintained over long evolutionary period
What is the most common fate of duplication?
Loss of function
- degeneration of a copy (can occur after of during duplication)
Sub-functionalization
Is a neutral mutation process in which each paralog retains a subset of its original ancestral gene
- degeneration of different modules in each copy (LOF)
- different functions are maintained after duplication
What do the duplicated genes in sub-functionalization do?
Together they fulfill the function of the original gene
- maintaining (purifying) selection acts on both copies
- allows for further specialization of functions
What is assumed in sub-functionalization?
Original gene contains multiple functions
What kind of selection does sub-functionalization use?
Purifying selection
Purifying selection
Is the selective removal of alleles that are deleterious
- selective pressures to maintain existing functions
Neo-functionalization
Is the perspective that all integration is the result of past integration
- evolution of new modules in one copy (one copy stays the same)
- the other copy acquires a new function
When may neo-functionalization occur?
Either during or after duplication
What kind of selection does neo-functionalization use?
Positive selection
Positive selection
Is the process by which new advantageous genetic variants sweep a population
How does neo-functionalization get a new gene copy?
Through translocation
Genome mining
Refers to deriving various information about the organism based on genome analysis
Sequence analysis
Is the process of subjecting a DNA, RNA or peptide sequence to nay of a wide range of analytical methods to understand its features, functions, structure or evolution
Expression profiling
Is the measurement of the activity of thousands of genes at once, to create a global picture of cellular function
What is intronnless and example of?
Hallmark
What were the steps for the retro-copies experiment? (6)
- Started off with a collection of all protein coding sequences (not the introns), including pseudogenes
- included known function of protein function sequences and suto regions - Used a set of mRNA sequences and performed a similar search against complete human genomes
- Found 4 hits without gaps
- This gave them a collection of all intronless genes in the human genome which would be candidates for retro copies
- this means that not all intronless genes are retro copies (which is why they looked further) - Took the candidates and did a similar sequence search but included the introns in the search
- looked fro additional hits that had gaps (at least 50% similar –> paralog) - Found 3,951 putatuve retro-copies
- of these, 705 (18%) were intact (the rest were pseudogenes
What does it mean if they found no gaps in their hit?
That no introns were in the sequence
- because introns creates gaps
What did it mean when they found intact sequence? (2)
- No premature stop codons
2. No frame shift mutations
Ks
Silent sites
Silent sites
Not changing encoded amino acids
- change DNA sequence though (but not the function)
Why should silent mutations accumulate over evolution?
Because they are under no selection and should accumulate over time based on mutation rate
Orthologs
Genes in a given species that evolved from a common ancestral gene by speciation
- retain same function
- results in 2 different species
Paralogs
The relationship between genes originating via genetic duplication
- results from same organism
- duplication
What Ks does most retro-copies have in humans?
0.05-0.25
What is Ks proportional to?
Time
Why does the curve decrease?
Because retro-copies became so dis-similar they were unable to be identified
- loss of retro-copies over time
What do primates diverge from?
Other mammals
What are 4 assumptions in the evolutionary fate to retry-copies?
- The new regulatory elements the retroposom gained drive new expression pattern (may allow neo-functionalization)
- If the duplicated is not important then the coding region of the retro copy should evolve neutrally
- eventually become a processed pseudogene - If the functionality of the original protein is adaptively important in both the old and the new is it expressed in the coding region and both should be under purifying selection
- If the duplicate in addition to its new expression also changes is protein function then the coding region of the retro-copy should be under positive selection
- coding region of parent should be under purifying selection
