Concerted evolution of class I genes in the major histocompatibility complex of murine rodents.

Abstract

Full-length cDNA sequences of two class I major histocompatibility complex molecules from the DA strain of Rattus norvegicus are reported. One codes for the classical class I restriction element RTL.Aa, which maps to the locus in the rat major histocompatibility complex homologous to H-2K in the mouse. The other probably codes for a soluble nonclassical class I molecule present in DA rat serum; a short deletion in the fifth exon implies that the translated product will terminate in the membrane-spanning region. These sequences have been compared with mouse classical class I sequences as well as with three published rat class I cDNA partial sequences. The results show, first, that "locus-specific" substitutions from the H-2K, H-2D, and H-2L data set are scrambled in the RTl.A molecule; a majority of these substitutions have H-2D/L-specific features. Second, the data show that the four rat sequences are strikingly similar to one another regardless of locus or haplotype of origin; they share a number of apparently species-specific features that distinguish them all from mouse classical class I sequences, which likewise share distinctive features of their own. The results suggest that segmental sequence exchange plays a major role in determining the evolution of sequence in class I masjor histocompatibility complex molecules.Some multigene families display a degree of species specificity at the level of DNA sequence, as if the whole family were evolving within a species as a unit (1-3). Such concerted evolution has been suspected in mouse major histocompatibility complex (MHC) class I genes because of the lack of clear locus-specific sequence variation distinguishing the widely separated H-2K and H-2D end classical loci (4, 5). Short segmental exchanges of sequence are indeed occurring between widely separated class I MHC loci in laboratory mice (6). Nevertheless it remains controversial whether such processes contribute significantly to the pattern of evolution of class I genes (7), since sequences of class I genes from a closely related murine species such as the rat are not yet available. Rattus norvegicus is in the same subfamily, the Murinae, as the mouse. The rat MHC, RTI, is like H-2 in structure, with a classical class I gene, RTJ.A, at the left end of the MHC in the same location as H-2K and a long array of other class I genes to the right (8). In the middle is a region specifying class II genes that closely resembles the homologous region of H-2 (9). It is most likely that the translocation of class I genes that formed the H-2K end was a unique event occurring shortly before the separation of the rat and mouse lineages (7). Rat class I gene sequences thus provide a stringent test of the concerted evolution hypothesis. With simple divergent evolution alone, the sequence of an RTI.A allele should have greater similarity to H-2K on average than to other rat class I sequences, since RTI.A and H-2K share a more recent common ancestor than either does with genes at the other end of the MHC. If, on the ot...

Transmembrane domain length variation in the evolution of major histocompatibility complex class I genes.

“…Interspecies comparison of MHC class I exon 5 sequences supports the hypothesis that gene conversion or segmental exchange is a feature of MHC class I gene evolution giving rise to species-specific DNA sequences and homogenization of multigene families (10,27,33). A putative example of this are the nucleotides sequences at positions %-100 in Pele-A genes (Fig.…”

“…A 13-bp deletion found in H-2Q10 genes is displaced from the Pele-A42c deletion by 3 nucleotides, and a 13-bp deletion in a rat MHC class I gene (RTBS.3.3; ref. 27, not shown in Fig. 1) starts 18 bp upstream of the Pele-A42c deletion.…”

“…24 and 25). (iii) H-2QI and RTl.Aa are clearly metalogous loci being found telomeric and centromeric, respectively, of class II genes (27,32). Thus the comparative analysis of exon 5 sequences implies that duplication events in this region are rather frequent occurrences in the evolution of rodent class I genes.…”

A Novel Instance of Class I Modification (cim) Affecting Two of Three Rat Class I RT1-A Molecules Within One MHC Haplotype

“…The identification in the rat RT1 o and RT1 d haplotypes of three well-expressed class I molecules, probably all of which are encoded in the class Ia (RT1-A) region of the MHC, stands in contrast to studies of other rat haplotypes in which MHC class Ia function appears to be mediated by one (30) or two (5) RT1-A region species. We were interested to know whether these three different A o molecules had similar capacities to act as target structures for T cell recognition.…”

“…While the latter two sequences have clearly diverged by ϳ10% at the nucleotide level throughout the coding sequence (overall, 92%; ␣1, 93%; ␣2, 87%; ␣3, 95%; TM/ IC, 92%), many unique sequence features common to them can be identified all along the open reading frame. The cDNA 3.6, which was isolated first from a library derived from a DA rat (RT1 av1 ), is expected to produce a soluble class I molecule, possibly that described by Spencer and Fabre (31), on account of a 13-nt deletion near the beginning of exon 5 (30). RT1-A3 o does not carry such a deletion and is therefore predicted to express transmembrane and intracytoplasmic domains similar to those of other class I molecules, except that it lacks the final 16 aa encoded by exon 7.…”