Dataset Information

Analysis of Sry duplications on the Rattus norvegicus Y-chromosome.

ABSTRACT: Gene copy number variation plays a large role in the evolution of genomes. In Rattus norvegicus and other rodent species, the Y-chromosome has accumulated multiple copies of Sry loci. These copy number variations have been previously linked with changes in phenotype of animal models such as the spontaneously hypertensive rat (SHR). This study characterizes the Y-chromosome in the Sry region of Rattus norvegicus, while addressing functional variations seen in the Sry protein products.Eleven Sry loci have been identified in the SHR with one (nonHMG Sry) containing a frame shift mutation. The nonHMGSry is found and conserved in the related WKY and SD rat strains. Three new, previously unidentified, Sry loci were identified in this study (Sry3BII, Sry4 and Sry4A) in both SHR and WKY. Repetitive element analysis revealed numerous LINE-L1 elements at regions where conservation is lost among the Sry copies. In addition we have identified a retrotransposed copy of Med14 originating from spliced mRNA, two autosomal genes (Ccdc110 and HMGB1) and a normal mammalian Y-chromosome gene (Zfy) in the Sry region of the rat Y-chromosome. Translation of the sequences of each Sry gene reveals eight proteins with amino acid differences leading to changes in nuclear localization and promoter activation of a Sry-responsive gene. Sry-? (coded by the Sry2 locus) has an increased cytoplasmic fraction due to alterations at amino acid 21. Sry-? has altered gene regulation of the Sry1 promoter due to changes at amino acid 76.The duplication of Sry on the Rattus norvegicus Y-chromosome has led to proteins with altered functional ability that may have been selected for functions in addition to testis determination. Additionally, several other genes not normally found on the Y-chromosome have duplicated new copies into the region around the Sry genes. These suggest a role of active transposable elements in the evolution of the mammalian Y-chromosome in species such as Rattus norvegicus.

SUBMITTER: Prokop JW

PROVIDER: S-EPMC3840628 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Analysis of Sry duplications on the Rattus norvegicus Y-chromosome.

Prokop Jeremy W JW Underwood Adam C AC Turner Monte E ME Miller Nic N Pietrzak Dawn D Scott Sarah S Smith Chris C Milsted Amy A

BMC genomics 20131114

<h4>Background</h4>Gene copy number variation plays a large role in the evolution of genomes. In Rattus norvegicus and other rodent species, the Y-chromosome has accumulated multiple copies of Sry loci. These copy number variations have been previously linked with changes in phenotype of animal models such as the spontaneously hypertensive rat (SHR). This study characterizes the Y-chromosome in the Sry region of Rattus norvegicus, while addressing functional variations seen in the Sry protein pr ...[more]

PMID: 24228692

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Project description:Sry is a gene known to be essential for testis determination but is also transcribed in adult male tissues. The laboratory rat, Rattus norvegicus, has multiple Y chromosome copies of Sry while most mammals have only a single copy. DNA sequence comparisons with other rodents with multiple Sry copies are inconsistent in divergence patterns and functionality of the multiple copies. To address hypotheses of divergence, gene conversion and functional constraints, we sequenced Sry loci from a single R. norvegicus Y chromosome from the Spontaneously Hypertensive Rat strain (SHR) and analyzed DNA sequences for homology among copies. Next, to determine whether all copies of Sry are expressed, we developed a modification of the fluorescent marked capillary electrophoresis method to generate three different sized amplification products to identify Sry copies. We applied this fragment analysis method to both genomic DNA and cDNA prepared from mRNA from testis and adrenal gland of adult male rats.Y chromosome fragments were amplified and sequenced using primers that included the entire Sry coding region and flanking sequences. The analysis of these sequences identified six Sry loci on the Y chromosome. These are paralogous copies consistent with a single phylogeny and the divergence between any two copies is less than 2%. All copies have a conserved reading frame and amino acid sequence consistent with function. Fragment analysis of genomic DNA showed close approximations of experimental with predicted values, validating the use of this method to identify proportions of each copy. Using the fragment analysis procedure with cDNA samples showed the Sry copies expressed were significantly different from the genomic distribution (testis p < 0.001, adrenal gland p < 0.001), and the testis and adrenal copy distribution in the transcripts were also significantly different from each other (p < 0.001). Total Sry transcript expression, analyzed by real-time PCR, showed significantly higher levels of Sry in testis than adrenal gland (p, 0.001).The SHR Y chromosome contains at least 6 full length copies of the Sry gene. These copies have a conserved coding region and conserved amino acid sequence. The pattern of divergence is not consistent with gene conversion as the mechanism for this conservation. Expression studies show multiple copies expressed in the adult male testis and adrenal glands, with tissue specific differences in expression patterns. Both the DNA sequence analysis and RNA transcript expression analysis are consistent with more than one copy having function and selection preventing divergence although we have no functional evidence.

Project description:Rat species Rattus norvegicus, also known as the brown street rat, is the most abundant mammal after humans in urban areas, where they co-exist with humans and domestic animals. The reservoir role of R. norvegicus of zoonotic pathogens in cities among rodent-borne diseases that could endanger the lives of humans and other mammals. Therefore, understanding the normal microbiome of R. norvegicus is crucial for understanding and preventing zoonotic pathogen transmission to humans and animals. We investigated the intestinal microbiome of free-living R. norvegicus collected from the Ruili, Nujiang, and Lianhe regions of Yunnan, China, using 16S rRNA gene sequence analysis. Proteobacteria, followed by Firmicutes, and Bacteroidetes were abundant in the intestines of R. norvegicus; however, bacterial compositions varied significantly between samples from different locations. Following a similar trend, Gammaproteobacteria, Bacilli, and Clostridia were among the top bacterial classes in most intestinal samples. The situation differed slightly for the Lianhe and Nujiang samples, although Phyla Bacteroidota and Spirochaetota were most prevalent. The Alpha diversity, Chao1, and Simpson indexes revealed microbial richness among the R. norvegicus samples. A slight variation was observed among the samples collected from Ruili, Nujiang, and Lianhe. At species levels, several opportunistic and zoonotic bacterial pathogens, including Lactococcus garvieae, Uruburuella suis, Bartonella australis, Clostridium perfringens, Streptococcus azizii, Vibrio vulnificus, etc., were revealed in the R. norvegicus intestines, implying the need for a regular survey to monitor and control rodent populations. In conclusion, we explored diverse microbial communities in R. norvegicus intestines captured from different regions. Further, we identified several opportunistic and potential bacterial pathogens, which still need to be tested for their underlying pathogenesis. The findings of our current study should be considered a warning to the health authorities to implement rat control and surveillance strategies globally.

Dataset Information

Analysis of Sry duplications on the Rattus norvegicus Y-chromosome.

Publications

Analysis of Sry duplications on the Rattus norvegicus Y-chromosome.

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