Discovery of eight novel divergent homologs expressed in cattle placenta

Abstract

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 ...

Multiple duplication of the bucentaur gene family, which recruits the APE-like domain of retrotransposon: Identification of a novel homolog and distinct cellular expression

“…reproduction system (Larson et al, 2006). p97Bcnt is expressed substantially in the spleen, small intestine, adrenal gland, ovary, and testis in goats (Fig.…”

Discovery and characterization of 91 novel transcripts expressed in cattle placenta

“…The divergent homologs were separated from the putative NTs by interrogating the sequences for distant homology in other species using BLASTX against non-redundant proteins (NCBI, April 2006), and TBLASTX against human and mouse UniGene (Build 190 and 152, respectively) and ESTs from other species (NCBI, April 2006). Sequences that aligned to database sequences below an empirically chosen E-value threshold of 10 -10 were designated as putative divergent homologs [12], and those that scored above this threshold were designated NTs. The NTs with similarity to cetartiodactyl-specific genes were identified by BLAST against a database of cetartiodactyl-specific non-redundant sequences and ESTs.…”

“…However, little is known about the role of divergent genes and lineage-specific transcripts in adaptive evolution. In ruminants, there is unequivocal evidence for lineage-specific and highly divergent genes expressed in the placenta and/or trophoblast e.g., genes encoding interferon-tau [9], the placental lactogens [10], the pregnancy associated glycoproteins [11] and the prolactin related proteins [12]. All of these highly divergent proteins appear to play adaptive roles in the reproductive biology of ruminants.…”

“…Toward that end, we recently developed a bioinformatics strategy to mine collections of expressed sequence tags (ESTs) for divergent homologs and novel transcripts [13]. This strategy led to the discovery of the ULBP gene cluster and eight divergent homologs in cattle [12,14]. Herein, we describe the application and extension of our approach for identifying and characterizing NTs expressed in mammalian tissues.…”

Placental Growth Hormone-Related Proteins and Prolactin-Related Proteins

“…Therefore, accelerated evolution of GH is observed in the absence of gene duplication. The cluster of PRL-like genes contains a gene expressed in the pituitary (PRL) and a 'placental lactogen' (PL), as well as prolactin-related proteins (PRPs) [47][48][49]. At least some, perhaps all, PRPs are expressed in the placenta.…”