ClonalEvolution
1 Introduction
MimicrEE2 supports the simulation of clonal evolution for haploid organism as well as for diploid organism.
Clonal evolution has the following properties
- clones do not need mates
- apart from de novo mutations, the progeny is identical to the parent
- no crossovers will occur
- no random assortment of chromosomes will occur
clones and sex?
Clones do not have sex. They are not looking for partners to mate with, thus specifying sexes for clones does not make sense. However, internally MimicrEE2 treats clones as hermaphrodites. Thus if sex specific effect sizes of SNPs are provided MimicrEE2 will use the effect of hermaphrodites. Specifying males or females during clonal evolution will result in an error!
Furthermore providing a sex-info or a recombination rate file for clonal evolution will also result in an error.
2 Clonal evolution with haploid organism
We need the following file:
haploid basepopulaion
In the following file we provide the haploid base population (hapbasepop.txt); specifying sex is not necessary (nor recommended) for simulations of clonal evolution. Internally MimicrEE2 treats clones as hermaphrodites, thus the sex hermaphrodite may be specified.
#sex H H H H H H H H H H H H H H H H H H H H 2L 1 G A/T A T A A A T A T A A A A A A A A T T T T 2L 2 G A/T A T A A A T A T A A A A A A A A T T T T 2L 3 G A/T A T A A A T A T A A A A A A A A T T T T 2L 4 G A/T A T A A A T A T A A A A A A A A T T T T 2L 5 G A/T A T A A A T A T A A A A A A A A T T T T 3R 6 G C/G C G C C C G C G C C C C C C C C G G G G 3R 7 G C/G C G C C C G C G C C C C C C C C G G G G 3R 8 G C/G C G C C C G C G C C C C C C C C G G G G 3R 9 G C/G C G C C C G C G C C C C C C C C G G G G 3R 10 G C/G C G C C C G C G C C C C C C C C G G G G
Note in this example we have two chromosomes; furthermore the allele A in chromosome 2L is always linked to the allele C in chromosome 3R; whereas the allele T in 2L is always linked to G in 3R; For simulations with sex, random assortment of chromosomes or recombination would quickly break this tight linkage appart. Not so with clonal evolution, we expect that this tight linkage persists.
simulations of clonal evolution
We perform neutral simulations for 50 generations and store the haplotypes in the folder output
java -jar mim2.jar w --haplotypes-g0 hapbasepop.mimhap --snapshots 5,10,20,30,40,50 --output-dir output --haploid --clonal
Note that it is necessary to provided both flags --haploid and --clonal for simulating clonal evolution of haploid organisms
output haplotpyes
at generation 10
The haplotypes with the alleles T in chr.2L and T in 3R decreased.
Note random assortment of chromosomes or recombination did not break up the strong linkage disequilibrium found in the base population (as expected for clonal evolution).
#sex H H H H H H H H H H H H H H H H H H H H 2L 1 G A/T A A A A A T A T T A T A A T T A A A A T 2L 2 G A/T A A A A A T A T T A T A A T T A A A A T 2L 3 G A/T A A A A A T A T T A T A A T T A A A A T 2L 4 G A/T A A A A A T A T T A T A A T T A A A A T 2L 5 G A/T A A A A A T A T T A T A A T T A A A A T 3R 6 G C/G C C C C C G C G G C G C C G G C C C C G 3R 7 G C/G C C C C C G C G G C G C C G G C C C C G 3R 8 G C/G C C C C C G C G G C G C C G G C C C C G 3R 9 G C/G C C C C C G C G G C G C C G G C C C C G 3R 10 G C/G C C C C C G C G G C G C C G G C C C C G
* at generation 20 *
the haplotype with A in chr.2L and C in 3R got fixed
#sex H H H H H H H H H H H H H H H H H H H H 2L 1 G A/T A A A A A A A A A A A A A A A A A A A A 2L 2 G A/T A A A A A A A A A A A A A A A A A A A A 2L 3 G A/T A A A A A A A A A A A A A A A A A A A A 2L 4 G A/T A A A A A A A A A A A A A A A A A A A A 2L 5 G A/T A A A A A A A A A A A A A A A A A A A A 3R 6 G C/G C C C C C C C C C C C C C C C C C C C C 3R 7 G C/G C C C C C C C C C C C C C C C C C C C C 3R 8 G C/G C C C C C C C C C C C C C C C C C C C C 3R 9 G C/G C C C C C C C C C C C C C C C C C C C C 3R 10 G C/G C C C C C C C C C C C C C C C C C C C C
3 Clonal evolution with diploid organism
MimicrEE2 supports simulating clonal evolution for diploid organism.
In this example we specify a positively selected overdominant locus.
The nice thing about clonal evolution is that it will not break up the advantageous overdominant allelic combination (No Hardy Weinberg).
diploid haplotypes
we store the following in file dipbasepop.mimhap
2L 1 G A/C CA AA AA AA AA CA AA CA AA AA 2L 2 G A/C CA AA AA AA AA CA AA CA AA AA 2L 3 G A/C CA AA AA AC AA CA AA CA AA AA 2L 4 G A/C CA AA CA AA AA CA AA CA AC AA 2L 5 G A/C CA AA AA AA CA CA AA AA AA AA 2L 6 G A/C AC AA AA AA AA AA AA AA AA AA 2L 7 G A/C AC AA AA CA CA AC AA AA AA AA 2L 8 G A/C AC AA AA AA AA AC AA AA AA AA 2L 9 G A/C AC AA AC AA AC AC AA AA CA AA 2L 10 G A/C AC AA AA AA CA AC AA AA AA AA
selected locus
We store the following content in file sellocus.txt
[w] 2L 6 A/C 0.5 1.2 0.8
Note the provided locus is highly overdominant for the genotype AC
run the simulations
java -jar mim2.jar w --haplotypes-g0 dipbasepop.mimhap --snapshots 5,10,20,30,40,50 --output-dir output --clonal --fitness sellocus.txt
Note we need to provide the flag --clonal (but not --haploid)
output haplotypes
at generation 5
The output may be viewed with the command gzip -cd output/haplotypes.r1.g5.mimhap.gz
The diploid individual with the overdominant locus increased slightly in frequency
#sex H H H H H H H H H H 2L 1 G A/C AA AA AA AA AA AA AA AA CA CA 2L 2 G A/C AA AA AA AA AA AA AA AA CA CA 2L 3 G A/C AA AA AA AA AA AA AA AA CA CA 2L 4 G A/C AC AA AC AA AA AC AC AC CA CA 2L 5 G A/C AA CA AA CA CA AA AA AA CA CA 2L 6 G A/C AA AA AA AA AA AA AA AA AC AC 2L 7 G A/C AA CA AA CA CA AA AA AA AC AC 2L 8 G A/C AA AA AA AA AA AA AA AA AC AC 2L 9 G A/C CA AC CA AC AC CA CA CA AC AC 2L 10 G A/C AA CA AA CA CA AA AA AA AC AC
at generation 20
The diploid individual with the overdominant genotype got fixed. All individuals are heterozygous. Note that with clonal evolution the genotypes get fixed rather than the alleles.
2L 1 G A/C CA CA CA CA CA CA CA CA CA CA 2L 2 G A/C CA CA CA CA CA CA CA CA CA CA 2L 3 G A/C CA CA CA CA CA CA CA CA CA CA 2L 4 G A/C CA CA CA CA CA CA CA CA CA CA 2L 5 G A/C CA CA CA CA CA CA CA CA CA CA 2L 6 G A/C AC AC AC AC AC AC AC AC AC AC 2L 7 G A/C AC AC AC AC AC AC AC AC AC AC 2L 8 G A/C AC AC AC AC AC AC AC AC AC AC 2L 9 G A/C AC AC AC AC AC AC AC AC AC AC 2L 10 G A/C AC AC AC AC AC AC AC AC AC AC
4 Clonal evolution with diploid organism and de novo mutations
In this example we simulate clonal evolution of a diploid organism.
We simualte a benefical mutations that is not present in the base population, but at some point it may appear in the popualtion as a de novo mutation.
haploid genomes
We store the following content in the file monomorphic.mimhap
2L 1 G A/C AA AA AA AA AA AA AA AA AA AA 2L 2 G A/T AA AA AA AA AA AA AA AA AA AA 2L 3 G A/G AA AA AA AA AA AA AA AA AA AA 2L 4 G A/C AA AA AA AA AA AA AA AA AA AA 2L 5 G A/T AA AA AA AA AA AA AA AA AA AA 2L 6 G A/C AA AA AA AA AA AA AA AA AA AA 2L 7 G A/C AA AA AA AA AA AA AA AA AA AA 2L 8 G A/T AA AA AA AA AA AA AA AA AA AA 2L 9 G A/G AA AA AA AA AA AA AA AA AA AA 2L 10 G A/C AA AA AA AA AA AA AA AA AA AA
Note that no SNPs are present in the base population.
selected locus
We simulate an overdominant locus at chromosome 2L position 6. We store the following content in the file sellocus.txt
[w] 2L 6 A/C 0.9 1.2 0.9
run the simulations
We run simulations with a mutation rate of 0.006 for 100 generations and request the evolved haplotypes as output each 10th generation.
java -jar mim2.jar w --haplotypes-g0 monomorphic.mimhap --snapshots 10,20,30,40,50,60,70,80,90,100 --output-dir output --clonal --fitness sellocus.txt --mutation-rate 0.0006
output haplotypes
at generation 60
The beneficial allele at position 6 appeared in the population due to a de novo mutation.
2L 1 G A/C CA CA CA CA CA CA CA CA CA CA 2L 2 G A/T AA AA AA AA AA AA AA AA AA AA 2L 3 G A/G AG AG AG AG AG AG AG AG AG AG 2L 4 G A/C AA AA AA AA AA AA AA AA AA AA 2L 5 G A/T AA AA AA AA AA AA AA AA AA AA 2L 6 G A/C AC AA AA AA AA AA AA AA AA AA 2L 7 G A/C AA AA AA AA AA AA AA AA AA AA 2L 8 G A/T AA AA AA AA AA AA AA AA AA AA 2L 9 G A/G AA AA AA AA AA AA AA AA AA AA 2L 10 G A/C AA AA AA AA AA AA AA AA AA AA
at generation 70
The beneficial SNP is rising in frequency.
2L 1 G A/C CA CA CA CA CA CA CA CA CA CA 2L 2 G A/T AA AA AA AA AA AA AA AA AA AA 2L 3 G A/G AG AG AG AG AG AG AG AG AG AG 2L 4 G A/C AA AA AA AA AA AA AA AA AA AA 2L 5 G A/T AA AA AA AA AA AA AA AA AA AA 2L 6 G A/C AC AA AC AC AC AC AC AC AC AC 2L 7 G A/C AA AA AA AA AA AA AA AA AA AA 2L 8 G A/T TA AA TA TA TA TA TA TA TA TA 2L 9 G A/G AA AA AA AA AA AA AA AA AA AA 2L 10 G A/C AA AA AA AA AA AA AA AA AA AA
at generation 80
The overdominant genotype at position 6 got fixed.
2L 1 G A/C CA CA CA CA CA CA CA CA CA CA 2L 2 G A/T AA AA AA AA AA AA AA AA AA AA 2L 3 G A/G AG AG AG AG AG AG AG AG AG AG 2L 4 G A/C AA AA AA AA AA AA AA AA AA AA 2L 5 G A/T AA AA AA AA AA AA AA AA AA AA 2L 6 G A/C AC AC AC AC AC AC AC AC AC AC 2L 7 G A/C AA AA AA AA AA AA AA AA AA AA 2L 8 G A/T TA TA TA TA TA TA TA TA TA TA 2L 9 G A/G AA AA AA AA AA AA AA AA AA AA 2L 10 G A/C AA AA AA AA AA AA AA AA AA AA
Note with clonal evolution genotypes get fixed rather than alleles
