3.2 Positive selection
Comparison of the genomes of the blue whale, the largest whale, with one of the smallest baleen whales, the minke whale identified several oncogenes undergoing positive selection. Using a pairwise positive selection assay of single gene orthologs (SGO), we identified 72 positively selected SGO in NA blue whales. Positively selected genes included; apoptotic signalling pathway (GO:0097190); programmed cell death (GO:0097468, GO:0010421, GO:0097190) genes XBP1, C17ORF47, PTH, SCG2 and PAWR ; genes that may have a role in the evolution of large body size such as the positive regulation of cell population proliferation (GO:0008284), growth genes (GO:0040007) and cell adhesion related genes. The positive regulator of cell population proliferation genes under positive selection included PDCD10 and CGA ; growth genes CCL28 , TROAP and STRC ; and cell adhesion related genes BASP1 , GAP43 , NPPA andCRLF3 . Further examination of the positively selected genes revealed that 69 of the 72 genes identified are associated with somatic mutation in cancer cells (COSMIC v90 fasta file, Forbes et al., 2015; also see Supplementary Information).
We further evaluated genomic regions under positive selection in the 12 present-day NA blue whales using Tajima’s D, and identified 52 additional genes under positive selection (Supplementary Information). The functional pathway analysis of the genes identified enrichment of nicotinic acetylcholine receptor (nAChR) signaling pathway, a pathway that regulates neurotransmitters that control cancer growth (Schuller, 2009) and genes, MYO6 , MYO1C and MYO10 (P00044) involved in hearing (Adamek, Geeves, & Coluccio, 2011; Heimsath et al., 2017; Roux et al., 2009). The enrichment of these genes can impact acoustic communication and may signal adaptation to low frequency sound amplification and detection in blue whales.
Functional analysis of positively selected genes also identified CEACAM1 (Takeuchi et al., 2019) and HAVCR2 (Gayden et al., 2018) which are involved in negative regulation of response to tumor cells (GO:0002835). Positively selected genes in the NA blue whales included GNAS, a regulator of insulin secretion in the mTOR signaling pathway which is involved in growth and diseases of aging (Blagosklonny et al., 2013).