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Rapid divergency of rodent CD99 orthologs: implications for the evolution of the pseudoautosomal region.
Park SH
,
Shin YK
,
Suh YH
,
Park WS
,
Ban YL
,
Choi HS
,
Park HJ
,
Jung KC
.
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The human pseudoautosomal region 1 (PAR1) is essential for the obligatory X-Y crossover in male meiosis. Despite its critical role, comparative studies of human and mouse pseudoautosomal genes have been limited owing to the scarcity of genes conserved between the two species. Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1. Although several sequences such as CD99L2, PBDX, and CD99L1 are related to CD99, its murine ortholog, Cd99, has not yet been identified. Here we report a novel mouse Cd99, designated D4, which shows overall sequence homology to CD99, with the highest conservation between the two genes being found in the transmembrane regions. In addition, the D4 protein displays biochemical characteristics, functional homology, and expression patterns similar to those of CD99. The D4 gene is localized on an autosome, chromosome 4, reflecting a common mapping feature with other mouse orthologs of human PAR1 genes. Furthermore, a phylogenetic analysis of CD99-related genes confirmed that the D4 gene is indeed an ortholog of CD99 and exhibits the accelerated evolution pattern of CD99 orthologs, as compared to the CD99L2 orthologs. On the basis of these findings, we suggest that CD99 belongs to the ancient PAR genes, and that the rapid interspecies divergence of its present sequence and map position is due to a high recombination frequency and the occurrence of chromosomal translocation, supporting the addition-attrition hypothesis for PAR evolution.
Fig. 5.
Amino acids alignment of the protein sequences for CD99 from different species: Homo sapiens CD99 (hCD99), Cercopithecus aethiops CD99 (cCD99), Mus musculus Cd99 (mCD99), Rattus norvegicus Cd99 (rCD99), Cricetulus griseus Cd99 (VAP21), Xenopus laevis cd99 (xCD99). Identical amino acids are indicated by black boxes, whereas conserved residues by gray boxes. Dashes indicate gaps in the amino acids alignment. The highly conserved regions are indicated in rectangular boxes. I, II, III denote âHighly conserved region I, II, IIIâ, respectively. P, G, TM indicates proline, glycine, and TM region, respectively.
Fig. 6.
Amino acids comparison and evolutionary relationship of family members of CD99. (A) Multiple alignment of amino acid sequences of Homo sapiens CD99 (hCD99), Cercopithecus aethiops CD99 (cCD99), Mus musculus CD99 (mCD99), Rattus norvegicus CD99 (rCD99), Cricetulus griseus CD99 (VAP21), Xenopus laevis CD99 (xCD99), H. sapiens CD99-like 2 (hCD99L2), M. musculus CD99-like 2 (mCD99L2), R. norvegicus CD99-like 2 (rCD99L2), Danio rerio CD99-like 2 (zCD99), and PBDX. Analysis and depiction of results were performed using the Clustal W multi-sequence alignment program. (B) Evolutionary relationship of members of CD99 and CD99-like 2 gene family and PBDX. Phylogenetic tree was generated from multiple amino acids alignment derived by Clustal W and displayed using TreeView (http://taxonomy.zoology.gla.ac.uk/rod/treeview.html). Evolutionary relationships are proportional to the branch distances. Database accession numbers used are NP_002405 (hCD99; H. sapiens CD99), U82164 (hCD99 type II; H. sapiens CD99 type II), U82165 (cCD99; C. aethiops CD99), AAB93833 (cCD99 type II; C. aethiops CD99 type II), AY262355 (mCD99; M. musculus CD99), AY262357 (rCD99; R. norvegicus CD99), AY262358 (xCD99; X. laevis CD99), XP_416858 (gCD99; Gallus gallus CD99), BP171855 (sCD99; Sus scrofa CD99), BJ004963 (oCD99; Oryzias latipes CD99), CK946723 (bCD99; Bos taurus CD99), AY078165 (hCD99L2; H. sapiens CD99-like 2) AY078163 (mCD99L2; M. musculus CD99-like 2), AF481858 (rCD99L2; R. norvegicus CD99-like 2), AY078168 (zCD99L2; D. rerio CD99-like 2), AAL04055 (PBDX).
Fig. 7.
Model for the evolution of the human and mouse PARs. A possible ancestral PAR and the present day PARs for human and mouse are shown. The PAR is represented by shaded and several fluctuating PAR genes are represented. Numbers indicates evolutionary stratum. Open white boxes mark X chromosome and yellow-hatched boxes chromosome Y. (A) First Y inversion (240â320 My); (B) Second Y inversion (130â170 My); (C) Translocation of a large autosomal region to the PAR of both X and Y: The generation of ancient PAR (80â130 My); (D) Third Y inversion (80â130 My); (E) Transposition of SRY into the ancestral PAR (50â66 My); (F) Fourth Y inversion (30â50 My); (G) Insertion of an Alu repeat element into the proximal PAR on the Y chromosome: the generation of Pseudoautosomal boundary (5â36 My); (H) Translocation of mouse PAR genes to autosomes and their attrition. My, million years before present.
