fundamental molecular lecture 3 genomes Flashcards
how do species share homologous genes?
by orthologs and paralogs
what are orthologs?
-by common descent, probably same function/ role
-hence study role in one species (ethically and costs allowed)
-and thus infer role in other species (where ethics, cost and practicalities might be an issue)
47% identity in protein sequence
(»>5%)Between yeast & Human gene
how do orthologs do the same job?
A human gene (CDC2) can take the place of a missing yeast gene (cdc2)
After ~1 billion years of evolution (since last common ancestor)
Look similar (encode a key cell cycle regulatory protein)
Really DO DO the SAME job: are interchangeable … Nobel Prize 2001
what are paralogs?
by duplication, probably diverged function/ role
what are between the spaces?
Brightly-coloured bits below line are repeated elements:
LINES (long interspersed nuclear elements)
SINES (short interspersed nuclear elements)
Transposons
LTRs (Long terminal repeats)
what are indels?
-they are insertions and deletions. they can be very small like 1-2bp and are surprisingly common
-can affect the protein product of a gene, if they occur in the protein coding region of a protein coding gene.
-can affect function of a ncRNA
-can affect regulatory regions
-most do not affect gene function, occur outside genes and in introns
what are micro and mini satellites?
Micro- ~1bp to 9bp repeating (“short tandem repeats” FORENSICS)
Mini- ~10bp to 100bp repeating
Relatively STABLE (generation to next) but highly variable in LENGTH (i.e., NUMBER of repeats) across alleles in the population
what is evolution?
a change in allele frequency in a gene pool / the change in allele frequency with time
what are CNVs (copy number variants)
there are a very surprising amount of CNVs variation in number of a segment of a chromosome, typically 500bp to 1 million bp segments.
what are SNPs (single nucleotide polymorphisms)?
rare snps= between 1-4.9% allele frequency
common snps= 5% allele frequency or more
Can affect the protein product of a gene if they occur in the protein-coding region (Open Reading Frame – ORF) of a protein-coding gene: silent, missense, nonsense
(MOST) do not cause a phenotype… occur outside genes, in introns etc…
Surprisingly common:A common SNP occurs approximately EVERY 1,000 bps in Human genome
how do point mutations/ variants range?
PRIVATE (to YOU): the ~200 de novo point mutations
FAIRLY COMMON (allele frequency of <1%) – call “VARIANT”
VERY COMMON (allele frequency of >1%) – “POLYMORPHISM”: Typically only 2 versions at a LOCUS (site in the genome) across the population(s):
how do you calculate allele frequency?
eg for allele frequency of A = no of A / total
what is the hardy-weinberg theory?
measuring the population at one timepoint = now.
For a given pair of allele frequencies, p and q: it predicts the GENOTYPE frequencies of diploids (humans, animals, plants..) assuming alleles are stable, a large homogeneous population, random mating and all genotypes are equally ‘fit’
what is the hardy-weinberg equation?
p2 + Ppq + q2 = 1
p2 = Frequency of AA homozygotes IF NO evolution
2pq = Frequency of Aa heterozygotes IF NO evolution
q2 = Frequency of aa homozygotes IF NO evolution
what does the hardy Weinberg equation find?
For a given pair of allele frequencies, p and q: it predicts the GENOTYPE frequencies that will keep that allele frequency constant from one generation to the next ie no evolution
what does it mean if allele frequency doesn’t change with time?
If allele frequency does not change with time: then the genotype frequencies ALSO stay constant at the predicted values. The system is at ‘equilibrium’
what does p + q = 1 mean?
where p= allele frequency of A and q= allele frequency of a
when should we work in decimals?
when finding the allele frequency. can convert to % at the end
what conclusions can we take from hardy-weinberg and observations?
if the predicted is equal to the observed, then the population is stable and not actively evolving
for most SNPs, what does the human population obey? (when no evolution)
random mating
homogeneous population (i.e., not stratified)
Population has not recently been small
Mutation between alleles occurring at v low frequency
NATURAL SELECTION is not occurring.
but what do some regions of the genome that are evolving follow?
-NON-random mating
-Population is not homogeneous (i.e., is stratified, immigration…)
-Population is or recently was small (i.e, sampling becomes an issue)
-Mutation between those alleles occurring at high frequency (unlikely .. But seen an example)
-NATURAL SELECTION is occurring.
