Unusually Similar Patterns of Antibody V Segment Diversity in Distantly Related Marsupials

Abstract

A pattern of coevolution between the V gene segments of Ig H and L chains has been noted previously by several investigators. Species with restricted germline VH diversity tend to have limited germline VL diversity, whereas species with high levels of germline VH diversity have more diverse VL gene segments. Evidence for a limited pool of VH but diverse VL gene segments in a South American opossum, Monodelphis domestica, is consistent with this marsupial being an exception to the pattern. To determine whether M. domestica is unique or the norm for marsupials, the VH and VL of an Australian possum, Trichosurus vulpecula, were characterized. The Ig repertoire in T. vulpecula is also derived from a restricted VH pool but a diverse VL pool. The VL gene segments of T. vulpecula are highly complex and contain lineages that predate the separation of marsupials and placental mammals. Thus, neither marsupial follows a pattern of coevolution of VH and VL gene segments observed in other mammals. Rather, marsupial VH and VL complexity appears to be evolving divergently, retaining diversity in VL perhaps to compensate for limited VH diversity. There is a high degree of similarity between the VH and VL in M. domestica and T. vulpecula, with the majority of VL families being shared between both species. All marsupial VH sequences isolated so far form a common clade of closely related sequences, and in contrast to the VL genes, the VH likely underwent a major loss of diversity early in marsupial evolution.

The opossum genome: Insights and opportunities from an alternative mammal

“…Past efforts to identify structural components of the metatherian immune system resulted in the detection of various genes and processes (e.g., major histocompatibility complex [MHC] genes, T-cell receptors, immunoglobulins, generation of antigenreceptor diversity via somatic V-D-J recombination) that sufficiently resembled those of humans and mice to suggest that the metatherian immunologic toolkit was generally similar to that of eutherian species (in the absence of comprehensive reviews, see Stone et al 1996Stone et al , 1998Miller and Belov 2000;Belov et al 2002aBelov et al ,b, 2004Belov et al , 2006Browning et al 2004;Miska et al 2004;Baker et al 2005;Gouin et al 2006b;Samollow 2006). Nevertheless, the vast evolutionary distance between the metatherian and eutherian clades made it difficult to identify metatherian homologs of genes within the more rapidly evolving components of the immune system, so the overall complexity and diversity of gene families in major arms of the immune system remained largely unknown.…”

On the genomics of immunoglobulins in the gray, short-tailed opossum Monodelphis domestica

“…A second IGHV subgroup, IGHV2 was also known but appeared to contain only a single gene segment. Both subgroups belong to clan III of mammalian IGHV, as do all marsupial IGHV isolated so far (Aveskogh et al 1999; Miller et al 1998; Baker et al 2005). …”

“…The content and diversity of expressed opossum Ig heavy and light chains have also been inferred from analysis of transcribed Ig mRNA (or cDNA) (Aveskogh et al 1998, 1999; Lucero et al 1998; Miller et al 1998, 1999). A number of observations emerged from these studies, including an apparent greater diversity of variable (V) gene segment subgroups in the light chains than in heavy, a pattern that appears to be common to other marsupial species as well (Baker et al 2005). Furthermore, the majority of expressed IGHV gene segments appeared to belong to a single V subgroup (Baker et al 2005; Miller et al 1998; Aveskogh et al 1999).…”

“…A number of observations emerged from these studies, including an apparent greater diversity of variable (V) gene segment subgroups in the light chains than in heavy, a pattern that appears to be common to other marsupial species as well (Baker et al 2005). Furthermore, the majority of expressed IGHV gene segments appeared to belong to a single V subgroup (Baker et al 2005; Miller et al 1998; Aveskogh et al 1999). A second IGHV subgroup, IGHV2 was also known but appeared to contain only a single gene segment.…”

Analysis of a set of Australian northern brown bandicoot expressed sequence tags with comparison to the genome sequence of the South American grey short tailed opossum

“…Although many marsupial genes have been identified using homology based approaches such as PCR and DNA-DNA hybridization, the low conservation of some genes makes them difficult to amplify and clone based solely on sequence similarity with homologs from other species [10-13]. Expressed sequence tags (ESTs) are single-pass, partial sequences of cDNA clones and have been used extensively for gene discovery and genome mapping in humans and other organisms [14-17].…”