Fig 3. Truncating mutations in erythrocyte-associated genes.

(A) Genes with truncating mutations or whole gene deletion in at least one icefish lineage. Asterisks indicate independent mutation events, with color corresponding to the allele above the cladogram. Δ indicates partial deletion of Hb in N. ionah with pseudogenization. See S5–S7 Figs for more detail on the Alas2, RhD and Hemgn mutations. See references 8–10 for analyses of the globin mutations. Arrow in A indicates position of red-blood cell (RBC) loss in icefishes (Channichthyidae) (B) Analysis of pleiotropy in erythroid genes (S4 Table). Genes were sorted by relative expression in mammalian erythrocytes vs other hematopoietic lineages and in mammalian bone marrow vs other organ systems. Genes were assigned a pleiotropy score ≥ 1 if mutations in these genes affect organ systems other than the hematopoietic system in the Mammalian Phenotype Ontology [74]. (C) Percentage of all erythroid-biased genes (S5 Table) with loss-of-function mutations in at least one lineage in icefishes (Channichthyidae) compared to other Antarctic notothenioid (Cryonotothenioids), showing enrichment for loss-of-function mutations in this gene set in species lacking red blood cells.