A cattle-human whole-genome comparative map was constructed using parallel radiation hybrid (RH) mapping in conjunction with EST sequencing, database mining for unmapped cattle genes, and a predictive bioinformatics approach (COMPASS) for targeting specific homologous regions. A total of 768 genes were placed on the RH map in addition to 319 microsatellites used as anchor markers. Of these, 638 had human orthologs with mapping data, thus permitting construction of an ordered comparative map. The large number of ordered loci revealed ը 105 conserved segments between the two genomes. The comparative map suggests that 41 translocation events, a minimum of 54 internal rearrangements, and repositioning of all but one centromere can account for the observed organizations of the cattle and human genomes. In addition, the COMPASS in silico mapping tool was shown to be 95% accurate in its ability to predict cattle chromosome location from random sequence data, demonstrating this tool to be valuable for efficient targeting of specific regions for detailed mapping. The comparative map generated will be a cornerstone for elucidating mammalian chromosome phylogeny and the identification of genes of agricultural importance. "Ought we, for instance, to begin by discussing each separate species-in virtue of some common element of their nature, and proceed from this as a basis for the consideration of them separately?" from Aristotle, On the Parts of Animals, 350 B.C.E.
Ten divergent homologs were identified using a subtractive bioinformatic analysis of 12,614 cattle placenta expressed sequence tags followed by comparative, evolutionary, and gene expression studies. Among the 10 divergent homologs, 8 have not been identified previously. These were named as follows: cattle cerebrum and skeletal muscle-specific transcript 1 (CSSMST1), cattle intestine-specific transcript 1 (CIST1), hepatitis A virus cellular receptor 1 amino-terminal domain-containing protein (HAVCRNDP), prolactin-related proteins 8, 9, and 11 (PRP8, PRP9, and PRP11, respectively) and secreted and transmembrane protein 1A and 1B (SECTM1A and SECTM1B, respectively). In addition, two previously known divergent genes were identified, trophoblast Kunitz domain protein 1 (TKDP1) and a new splice variant of TKDP4. Nucleotide substitution analysis provided evidence for positive selection in members of the PRP gene family, SECTM1A and SECTM1B. Gene expression profiles, motif predictions, and annotations of homologous sequences indicate immunological and reproductive functions of the divergent homologs. The genes identified in this study are thus of evolutionary and physiological importance and may have a role in placental adaptations. molecular evolution; bovine genome; comparative genomics THE PLACENTA DEMONSTRATES remarkable variation among eutherian mammals, and it is believed that the vast diversity of placental architectures seen in different mammalian lineages is the result of adaptive evolution (8, 47). Two major selective forces likely driving adaptation of the placenta are fetalmaternal conflict over nutrient resource allocation and maintenance of immunologic tolerance of the fetal semi-allograft (45,66). Cattle possess a synepitheliochorial placenta arranged as placentomes consisting of a fetal cotyledon interdigitating with a maternal caruncle. The cattle embryonal trophoblast contains granulated binucleate cells at the microvillar junction with cytoplasmic projections that penetrate the maternal uterine endometrium (70, 72). Ruminant-specific genes with expression localized to the trophoblast have been identified, including the interferon-genes (54) The expression of these genes at sites of direct contact between fetal and maternal cells suggests that they represent molecular adaptations mediating maternal-fetal interaction during pregnancy (8,55).Comparisons between the whole genome sequences of human, mouse, and rat revealed extensive lineage-specific expansions in gene families associated with reproduction, immunity, chemosensation, detoxification, and proteolysis (48, 52). The identification of orthologous relationships for ϳ80% of genes in the human and mouse genomes indicates that lineagespecific gene family expansion likely represents a major route of mammalian evolution. These lineage-specific paralogs are believed to represent adaptive innovations on the basis of evidence that positive selection has operated on a subset of proteins functioning in reproduction and immunity (48). It is likely that the ...
A whole genome cattle-hamster radiation hybrid cell panel was used to construct a map of 54 markers located on bovine chromosome 5 (BTA5). Of the 54 markers, 34 are microsatellites selected from the cattle linkage map and 20 are genes. Among the 20 mapped genes, 10 are new assignments that were made by using the comparative mapping by annotation and sequence similarity strategy. A LOD-3 radiation hybrid framework map consisting of 21 markers was constructed. The relatively low retention frequency of markers on this chromosome (19%) prevented unambiguous ordering of the other 33 markers. The length of the map is 398.7 cR, corresponding to a ratio of Ϸ2.8 cR 5,000͞cM. Type I genes were binned for comparison of gene order among cattle, humans, and mice. Multiple internal rearrangements within conserved syntenic groups were apparent upon comparison of gene order on BTA5 and HSA12 and HSA22. A similarly high number of rearrangements were observed between BTA5 and MMU6, MMU10, and MMU15. The detailed comparative map of BTA5 should facilitate identification of genes affecting economically important traits that have been mapped to this chromosome and should contribute to our understanding of mammalian chromosome evolution.radiation hybrid ͉ expressed sequence tag ͉ BTA5 ͉ HSA12
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