Differential loss of embryonic globin genes during the radiation of placental mammals

Abstract

The differential gain and loss of genes from homologous gene families represents an important source of functional variation among the genomes of different species. Differences in gene content between species are primarily attributable to lineage-specific gene gains via duplication and lineage-specific losses via deletion or inactivation. Here, we use a comparative genomic approach to investigate this process of gene turnover in the beta-globin gene family of placental mammals. By analyzing genomic sequence data from representatives of each of the main superordinal clades of placental mammals, we were able to reconstruct pathways of gene family evolution during the basal radiation of this physiologically and morphologically diverse vertebrate group. Our analysis revealed that an initial expansion of the nonadult portion of the beta-globin gene cluster in the ancestor of placental mammals was followed by the differential loss and retention of ancestral gene lineages, thereby generating variation in the complement of embryonic globin genes among contemporary species. The sorting of epsilon-, gamma-, and eta-globin gene lineages among the basal clades of placental mammals has produced species differences in the functional types of hemoglobin isoforms that can be synthesized during the course of embryonic development.

Fig. 1.

Genomic structure of the β-globin gene cluster in therian mammals. Phylogenetic relationships are based on a loose consensus of recent studies (21, 22, 49, 50). Diagonal slashes indicate gaps in genomic coverage. Segments containing such gaps were not drawn to scale. The orientation of the cluster is from 5′ (on the left) to 3′ (on the right).

Fig. 2.

Maximum likelihood phylograms depicting relationships among β-like globin genes in species of the superorder Atlantogenata based on 1 kb of 5′ flanking sequence (Left), intron 2 (Center), and 1 kb of 3′ flanking sequence (Right). Bootstrap support for the relevant nodes was evaluated by using 1,000 pseudoreplicates.

Fig. 3.

Maximum likelihood phylograms depicting relationships among β-like globin genes in species of the superorder Laurasiatheria based on 1 kb of 5′ flanking sequence (Left), intron 2 (Center), and 1 kb of 3′ flanking sequence (Right). Bootstraps support for the relevant nodes was evaluated by using 1,000 pseudoreplicates.

Fig. 4.

A model describing the evolution of the β-globin gene family in eutherian mammals. According to this model, two successive duplications of a proto-HBE gene gave rise to the HBG and HBH genes in the ancestor of eutherian mammals after divergence from marsupials. Consequently, the full complement of embryonic globin genes—HBE-HBG-HBH—was present in the common ancestor of the two main clades of eutherian mammals, Boreoeutheria (comprising Euarchontoglires and Laurasiatheria) and Atlantogenata (comprising Xenarthra and Afrotheria). Subsequent to the Boreoeutheria–Atlantogenata split (≈105 Mya), the HBH gene was deleted in the common ancestor of xenarthrans and afrotherians, and the HBG gene was lost in xenarthrans after divergence from the afrotherian lineage (≈95 Mya). The ancestral three-gene set was also present in the common ancestor of Euarchontoglires and Laurasiatheria. Subsequent to the divergence of these two groups (≈85 Mya), the HBG gene was lost in laurasiatherians and the HBH gene was lost in Euarchontoglires. Latin crosses denote lineage-specific gene losses, either via deletion or inactivation.