Cyp6 cluster UGS

Haplotype analyses of the CYP6 cluster in Anopheles gambiae samples from Uganda (UGS), using Ag1000G Phase 1 data.

Input

Download Ag1000G Phase 1 data from here

ftp://ngs.sanger.ac.uk/production/ag1000g/phase1/AR3.1

Contents

Notebooks:

• 2020-02-27_hap_analysis_UGS_sweep.ipynb: notebook with analysis of haplotype similarity and selection signals in UGS. The cluster of swept haplotypes is defined using genetic distances of genotypes located +/- 1000 variants around the Cypaa1 start coordinate (results taken from sweep_haplotypes.csv). Selection statistics are estimated for the Cyp6 custer (EHH, Garud H, hap diversity). Results and plots go to folder results_sweep.

• results_phylogeny: phylogenies of haplotypes using variants in the cluster (using IQTREE). Results in newick (.treefile) & pdf.

• in folder other/, there is another notebook I used to do a quick analysis of haplotype networks built around another variant of interest, 2R:28491424, which was in LD with both the duplication and the ZZB insertion in UGS. I wanted to see if we can find it elsewhere in the Ag1k samples, but it's not there, so this is not useful. Results go to results_TAG.

Results

Main cluster

Phylogeny & haplotype cluster shows a group of swept haplotypes with strong signals of selection. It contains the following genotypes:

• all sequences have the I236M mutation
• all sequences have the zzb transposon OR come from genomes that have it (het)
• all sequences have the indel OR come from genomes that have it (het)
• it contains sequences from specimens with and without duplication (including duplicated homozygotes).
• all of them have the tagging variant that is in LD with the duplication and zzb (tag1 in sequence name)

Therefore, the selective sweep occurred after the I236M, zzb insertion and indels; but before the duplication occurred. This is consistent with the late emergence of the duplication (2009) relative to other mutations (zzb in 2004, I236M in 2005).

Secondary cluster

There is a second cluster of highly similar haplotypes that do not have any resistance mutations. This cluster has signals of selection too. Not explored right now.