Meiosis stages
- Chromosomes become shorter and thicker; chiasmata are prominent
- Homologous chromosomes repel; they are held together by chiasmata
- Bivalents align on the metaphase plate
- Homologous chromosomes separate
- Chromosomes align on the metaphase
What happens when bivalents lack the chiasmata
They are prone to nondysjunction where you don’t get proper segregation of the chromosomes into the gametes at the end, you don’t get recombination
Why is meitotic recombination of fundamemental importance
- It generates new combinations of genotypes which is essential for adaptation/ natural selection
- Determines to what extent loci residing in different genomic locations are associated with one another (linkage)
- Crossover is critical for correct segregation of chromosomes during meiosis but its also really important for mixing genetic material between the maternal and the paternal genomes so the gametes aren’t identical to the parental genome
What is linkage disequilibrium
The extent to which the allele frequencies at two loci are correlated.
What does recombination do to LD
It breaks down LD which makes selection more efficient because it allows new and more favourable mutations to be more integrated into the population together and it allows selection to eliminate deleterious combinations
What is background selection
Selection is going to act to purge those from the population. All the black lines (chromosomes are going to be lost from the population because they have a lower fitness leaving behind deleterious mutations.
Therefore in the next generation, this means that mutations can occur and become weakly linked with the deleterious mutation.
So therefore we get fixation of this bad mutation because you can’t have recombination to shuffle the mutations between the different chromosomes in order to create a mutation free chromosome .
Mullers Rachets
there’s no recombination so there’s no shuffling of mutations between different chromosomes - what happens is there’s this stochastic loss of mutation free chromosome (purely by chance) - your population then starts to accumulate these deleterious mutations
Genetic hitchhiking
deleterious mutations along with a beneficial mutation, there’s selection for the strongly beneficial mutation (positive fitness effect) however, its in LD with a deleterious mutation so as well as the beneficial mutation getting fixed, the deleterious one also does as well - can separate that linkage between the beneficial and the deleterious mutation.
Ruby in the Rubbish
Opposite of the last where you get beneficial mutations that have been lost from the population simply because they’re linked with a really deleterious mutation that’s going to be eliminated from the population (lose those deleterious mutations)
What’s the variation of recombination rates like across species
There’s huge recombination rate variations
This is strange because recombination is fundamental so why are some species doing it more and some doing it less? This may have implications for how efficient selection
Its important that we start to measure the intensity of recombination and its evolutionary significance due to the variation
Where are the variations in recombination
Across a species
Across males and females of a species (between individuals
Across the genome
Across the chromosomes
What is the genetic distance and how is it measured
The degree of genetic linkage between two loci is measured by the frequency of recombination between two loci
- c ranges between 0
(complete linkage) to 0.5 (independent
assortment or unlinked)
– The standard unit is cM (centi-Morgan)
– 1 cM = 1% probablilty of producing a recombinant
What do we need to consider
- The genetic distance between locus A and locus B is 17cM, and so is that between locus C and locus D. (you can work out genetic distance by dividing the genetic distance by the physical distance- related but there’s no direct correlation between the two )
- But the physical distance between the the first pair of loci is 10 Mb, and that between the second pair is 50 Mb
What is the recombination rate
- Standard unit: cM/Mb (or cM Mb-1)
- A measure of recombination
propensity per genomic length unit
Example calculation for genetic distance
- Between A and B: 17cM/10Mb = 1.7cM/Mb- recombination rate is higher which makes sense because they’re closer together (not a linear correlation)
- Between C and D: 17cM/50Mb =
0.34cM/Mb - The average rate is higher between A and B
Iceland case study
- 5,136 microsatellite markers (as genetic markers)
– 869 individuals in 146 Icelandic families (pedigree-based) - Were able to measure 1,257 meioses
- Obtained recombination rates by mapping the markers to the genome
sequence (there are 3billion base pairs in the human genome, calculated the recombination rate- divided genetic distance by the physical distance) - The total length of the sex-averaged genetic map: 3,615 cM (22
autosomes and the X) - Genome size ≈ 3×109 = 3,000 Mb
- Mean sex-averaged rate ≈ 1.205 cM/Mb
Variation in recombination rate between chromosomes
-Shorter chromosomes tend to have high recombination rates
– E.g., the average rates of chr 21 and 22 are twice as high as those of
chr 1 and 2.
– Each bivalent usually has at least one chiasma for proper disjunction
during meiosis
- Sex-averaged recombination rates tend to be higher towards telomeres and lower at centromere-
Also see huge variation - not specific to humans
- Sperm crossovers occur across the region at 0.9 cM/Mb
- The great majority (about 94%) of crossovers lie within hotspots, with 72%
in hotspot DNA3 (narrow 1-2kb regions) - Hotspots are not randomly distributed but fall into clusters 60–90 kb apart
- Hotspots vary considerably in peak intensity
Myers et al. (2005; Science)
A human genome-wide data set with ~1.6 million SNPs
– The fine-scale recombination landscape is dominated by
recombination hotspots
– 80% of the recombination occurs in 10 to 20% of the sequence
Kong et al., Nature, 2010
The Basonuclin-2 gene on chromosome 9
* Recombinations in this region are dominated by those resulting from male
meiosis.
Males and females are recombing at different extents- females aren’t recombining huge amounts
Whereas there’s a lot of recombination in males- can see these big hotspots
Males and females- very striking difference in recombination.
No recombination is happening when eggs are produced in females
Recombination variation on chromosomes in males and females
the location of these hotspots differs in males and females
Recombination is higher in females but females recombine evenly across the whole chromosome
In males there’s a really strong effect of physical location, so they recombine more highly towards the ends of the chromosome than the centromere in the middle - don’t know why this variation exists
Humans versus chimps (Auton et al. 2012; Science)
Overall genome-wide divergence = 1.23%
– The genomes of 10 Western chimpanzees
At the level of entire chromosomes, recombination rates are very similar in
humans and chimpanzees, with the exception of chromosome 2
– Human chromosome 2 which originated from a telomeric fusion of chimp
chr2a and chr2b in the human ancestral lineage
- No evidence of sharing of hotspots between species
What determines the location of a hotspot
Search for specific sequence features (motifs) in hotspots
Recombination is important for determining the efficacy of selection
Myers et al. (Nat Genet, 2008)
This study mapped a recombination rate across lots of different individuals
They Identified 22,599 autosomal and 608 X-linked hotspots
– They found a A degenerate 13-mer CCNCCNTNNCCNC highly enriched in recombination
hotspots
– 41% (±1.4%) of all human hotspots is determined by the
presence of the motif- plays an important role in the determination of these hotspots
