Emergence of a Chimeric Globin Pseudogene and Increased Hemoglobin Oxygen Affinity Underlie the Evolution of Aquatic Specializations in Sirenia

Abstract

As limits on O ₂ availability during submergence impose severe constraints on aerobic respiration, the oxygen binding globin proteins of marine mammals are expected to have evolved under strong evolutionary pressures during their land-to-sea transition. Here, we address this question for the order Sirenia by retrieving, annotating, and performing detailed selection analyses on the globin repertoire of the extinct Steller’s sea cow ( Hydrodamalis gigas), dugong ( Dugong dugon), and Florida manatee ( Trichechus manatus latirostris) in relation to their closest living terrestrial relatives (elephants and hyraxes). These analyses indicate most loci experienced elevated nucleotide substitution rates during their transition to a fully aquatic lifestyle. While most of these genes evolved under neutrality or strong purifying selection, the rate of nonsynonymous/synonymous replacements increased in two genes ( Hbz-T1 and Hba-T1) that encode the α-type chains of hemoglobin (Hb) during each stage of life. Notably, the relaxed evolution of Hba-T1 is temporally coupled with the emergence of a chimeric pseudogene ( Hba-T2/Hbq-ps) that contributed to the tandemly linked Hba-T1 of stem sirenians via interparalog gene conversion. Functional tests on recombinant Hb proteins from extant and ancestral sirenians further revealed that the molecular remodeling of Hba-T1 coincided with increased Hb–O ₂ affinity in early sirenians. Available evidence suggests that this trait evolved to maximize O ₂ extraction from finite lung stores and suppress tissue O ₂ offloading, thereby facilitating the low metabolic intensities of extant sirenians. In contrast, the derived reduction in Hb–O ₂ affinity in (sub)Arctic Steller’s sea cows is consistent with fueling increased thermogenesis by these once colossal marine herbivores.