Dataset Information

Haplotype distribution and evolutionary pattern of miR-17 and miR-124 families based on population analysis.

ABSTRACT:

Background

MicroRNAs (miRNAs) are small, endogenously expressed non-coding RNAs that regulate mRNAs post-transcriptionally. Previous studies have explored miRNA evolutionary trend, but evolutionary history and pattern in the miRNA world are still not fully clear. In the paper, we intended to analyze miRNA haplotype distribution and evolutionary network by analyzing miRNA sequences of miR-17 and miR-124 families across animal species as special populations.

Principal findings

31 haplotypes were detected in miR-17 family while only 9 haplotypes were defined in miR-124 family. The complex miR-17 family was mainly distributed in vertebrates, but miR-124 was shared by more animal species from Caenorhabditis to Homo and had a wide distribution spectrum. Some haplotypes of the two miRNA families appeared discontinuous distributions across animals. Compared with a simple phylogenetic network in miR-124 family, miR-17 family indicated a complex network with some median vectors that might be lost ancestral or potential miRNA haplotypes. By analyzing different miRNAs across 12 animal species, we found these small RNAs showed different haplotype diversities, haplotype distributions and phylogenetic networks.

Conclusions

Different miRNAs had quite different haplotype distributions and evolutionary patterns. Discontinuous distributions of miRNAs and median vectors in phylogenetic networks implied more members in the miRNA world. miRNA may be an excellent phylogenetic marker to discover its evolutionary history and pattern across the animal kingdom.

SUBMITTER: Guo L

PROVIDER: S-EPMC2775919 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIn older adults (aged 70-74 years), African-Americans have 4-fold higher risk of developing hypertension-attributed end-stage renal disease (ESRD) than European-Americans. A hypothesized mechanism linking hypertension and progressive chronic kidney disease (CKD) is the innate immune response and inflammation. Persons with CKD are also more susceptible to infection. Gene expression in peripheral blood can provide a view of the innate immune activation profile. We aimed to identify differentially expressed genes, microRNAs, and pathways in peripheral blood between cases with CKD and high blood pressure under hypertension treatment versus controls without CKD and with controlled blood pressure in African Americans.MethodsCase and control pairs (N = 15x2) were selected from those without diabetes and were matched for age, sex, body mass index, APOL1 risk allele count, and hypertension medication use. High blood pressure under hypertension treatment was defined as hypertension medication use and systolic blood pressure (SBP) ≥ 145 mmHg. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2. Cases were selected from those with CKD and high blood pressure under hypertension treatment, and controls were selected from those without CKD (eGFR: 75-120 mL/min/1.73m2 and urine albumin-to-creatinine ratio < 30mg/g) and with blood pressure controlled by hypertension medication use (SBP < 135 mmHg and D(diastolic)BP < 90 mm Hg). We perform RNA sequencing of mRNA and microRNA and conducted differential expression and co-expression network analysis.ResultsOf 347 miRNAs included in the analysis, 14 were significantly associated with case status (Benjamini-Hochberg adjusted p-value [BH p] < 0.05). Of these, ten were downregulated in cases: three of each belong to the miR-17 and miR-15 families. In co-expression network analysis of miRNA, one module, which included 13 of the 14 significant miRNAs, had significant association with case status. Of the 14,488 genes and 41,739 transcripts included in the analysis, none had significant association with case status. Gene co-expression network analyses did not yield any significant associations for mRNA.ConclusionWe have identified 14 differentially expressed miRNAs in the peripheral blood of CKD cases with high blood pressure under hypertension treatment as compared to appropriate controls. Most of the significant miRNAs were downregulated and have critical roles in immune cell functions. Future studies are needed to replicate our findings and determine whether the downregulation of these miRNAs in immune cells may influence CKD progression or complications.