Gene loss in Antarctic icefish: evolutionary adaptations mimicking Fanconi Anemia?

Abstract

Background: The white-blooded Antarctic icefishes is a representative organism that survive under the stenothermal conditions of the Southern Ocean without the hemoglobin genes. To compensate for inefficient oxygen transport, distinct features such as increased heart size, greater blood volume, and reduced hematocrit density enhance the amount of dissolved oxygen and the velocity of blood flow.

Results: Here, we investigated these unique characteristics by comparing high-quality genomic data between white-blooded and red-blooded fishes and identified the loss of FAAP20, which is implicated in anemia. Although the gene region containing FAAP20 is conserved in notothenioids as shown through collinear analysis, only remnants of FAAP20 persist in several icefish species. Additionally, we observed the loss of SOAT1, which plays a pivotal role in cholesterol metabolism, providing a clue for further investigations into the unique mitochondrial form of the icefish.

Conclusions: The loss of FAAP20, which is known to reduce erythrocyte counts under stress conditions in mice and humans, may provide a clue to understanding the genomic characteristics related to oxygen supply, such as low hematocrit, in Antarctic icefishes.

Keywords: FAAP20; Antarctic icefish; Fanconi anemia; Gene loss.

Fig. 1

Protein-based collinearity analysis and OGs in Antarctic notothenioids. (a) Collinearity analysis of seven chromosome-scale genomes from Antarctic and sub-Antarctic fish. Each chromosome is numbered with Roman numerals, except for those of Eleginops maclovinus and Champsocephalus esox, which are numbered with Arabic numerals. For Notothenia rossii, 12 chromosomes, organized by their NCBI accession numbers, are presented for comparison. (b) A total of 11,461 orthologous groups were identified across all fish, while 8 orthologous groups were found exclusively in red-blooded fish and not in white-blooded icefishes. (c) Phylogenetic tree (left) depicting the evolutionary relationships among nine notothenioid species, highlighting the divergence between Antarctic and sub-Antarctic lineages. Branches are color-coded by lineage: Antarctic icefish (blue), red-blooded notothenioids (red), and their related species (green). The ultrametric tree includes divergence times and marks each species with closed circle for specific evolutionary traits, highlighting the presence of antifreeze glycoprotein (AFGP), and the number of orthologous groups for each lineage. For the 8 genes not found in white-blooded icefish, the presence or absence of the genes was indicated by closed circles and open circles. All species presented are part of the Antarctic notothenioid clade, except for C. gobio and E. maclovinus which are members of two out of the three non-Antarctic notothenioid families

Fig. 2

Analysis of FAAP20 loss in Antarctic icefish. (a) Fanconi anemia (FA) repair pathway depicting the FA core complex, including FANCA, B, C, D, E, F, G, L, M, and accessory components (FAAP20, FAAP24, FAAP100). The ID complex comprises FANCI, FANCD2, and FAN1, whereas BRIP1 functions in the effector complex. The FA core complex, through FANCM, recognizes interstrand crosslink (ICL) lesions and monoubiquitinates the ID complex (FANCI and FANCD2), which subsequently recruits the effector complex to break the crosslink. (b) Fifteen orthologous groups linked to Fanconi anemia. (c) Gene regions between the SKI and FLNA loci on the orthologous chromosomes or contigs of the eight fish species. Each horizontal line depicts the chromosome span, arranged from the 5′ to 3′ orientation. Colored arrows depict various genes, with each color representing a different gene within the locus. FAAP20 region is split into two contigs in G. acuticeps: NW_022991958.1 and NW_022992339.1. (d) Gene region containing FAAP20 identified in a syntenic block based on the orthologous protein group. The FAAP20 region is located on the orthologous chromosomes in five Antarctic fish (N. rossii, C. gunnari, C. esox, C. aceratus, and P. georgianus) and on OX449114.1 in N. rossii. Collinearity is visualized to focus on the chromosome length proportion within each species, with the gray region depicting the syntenic block containing the FAAP20 locus. (e) FAAP20 spanning approximately 10–12 kb on the chromosome, with the FAAP20 protein (ranging from 251–255 amino acids in length) translated from 4 or 5 exons

Fig. 3

Hypothesis regarding the effect of FAAP20 loss on erythropoiesis. (a) The development of the hematopoietic lineage in a typical fish model (upper panel). In fish, red blood cells are nucleated. The presence of FAAP20 results in the normal differentiation of erythrocyte from hematopoietic stem cells (HPSCs) in Antarctic fish. (b) Contrastingly, the diagram (lower panel) illustrates the hypothesis regarding the effect of FAAP20 loss on the predicted development of the hematopoietic lineage in Antarctic icefish. The absence of FAAP20 may reduce the common myeloid progenitor and GMP in the erythroid progenitors, similar to that in the FAAP^−/−mouse model. Additionally, the evolution of the erythrocyte-associated conserved non-coding elements affects the differentiation of the HPSC into erythrocytes, resulting in the breakdown of the erythropoietic process and anemia in Antarctic icefish. FAAP20 loss in Antarctic fish might be a factor contributing to pancytopenia in the erythroid progenitors