Extended Data Fig. 2: Loss of heterozygosity regions have sub-lineage-specific founder variants.
(a) Comparative sizes of the assembled genome and the fractions called as LOH in the PEI (red) and USA (blue) sub-lineages. (b) SNV density of sub-lineage-specific founder variants (variants found in a healthy clam and all individuals of one sub-lineage but none in the other sub-lineage) across the genome and LOH regions called in the other sub-lineage. Density is 36× greater for PEI mutations in USA LOH regions versus non-LOH regions and 20x greater for USA mutations in PEI LOH regions versus non-LOH regions. LOH regions were ignored for somatic mutation analysis to reduce the influence of remaining founder variants in sub-lineage specific SNVs, which should otherwise consist of somatic mutations. (c) We used various thresholds of stringency to call LOH across the genomes of each sub-lineage based on the number of shared SNVs that were homozygous in one sub-lineage but heterozygous in the other across a window of 50 SNVs (x-axis). After calling LOH, we calculated the fraction of likely somatic mutations attributed to signature S in LOH (squares) and non-LOH (circles) (y-axis). Values are shown separately for the BTN subgroups from USA (blue) and PEI (red). Vertical dashed line indicates the threshold used for LOH-calling. Horizontal dashed lines indicated baseline signature S fractions without LOH region removal. (d) Plot of the difference between non-LOH and LOH regions as shown in (c) (calculated by subtracting the square from the circle). Black line shows the average difference, which peaks around the threshold used (10). (e) Proportion of the genome that is called LOH for each sub-lineage based on calling threshold. Dashed lines indicate the fraction of the genome called as LOH for each sub-lineage for the final threshold used.
