Tandem Duplicate Genes in Maize Are Abundant and Date to Two Distinct Periods of Time

Tandem duplicate genes are proximally duplicated and as such occur in similar genomic neighborhoods. Using the maize B73 and PH207 de novo genome assemblies, we identified thousands of tandem gene duplicates that account for ∼10% of the annotated genes. These tandem duplicates have a bimodal distribution of ages, which coincide with ancient allopolyploidization and more recent domestication. Tandem duplicates are smaller on average and have a higher probability of containing LTR elements than other genes, suggesting origins in nonhomologous recombination. Within relatively recent tandem duplicate genes, ∼26% appear to be undergoing degeneration or divergence in function from the ancestral copy. Our results show that tandem duplicates are abundant in maize, arose in bursts throughout maize evolutionary history under multiple potential mechanisms, and may provide a substrate for novel phenotypic variation

Abstract: Evaluation of the biomarker Dickkopf 3 in more than 1100 CKD patients of a German single center cohort using algorithm-based data analysis

Objective: Dickkopf 3 (DKK3) has been identified as a urinary biomarker. Values above 4000 pg/mg creatinine (Cr) were linked with a higher risk of short-term decline of kidney function (J Am Soc Nephrol 29: 2722–2733). However, as of today, there is little experience with DKK3 as a risk marker in everyday clinical practice. We used algorithm-based data analysis to evaluate the potential dependence of DKK3 in a cohort from a large single center in Germany. Method: DKK3 was measured in all CKD patients in our center October 1 st 2018 till Dec. 31 2019, together with calculated GFR (eGFR) and urinary albumin/creatinine ratio (UACR). Kidney transplant patients were excluded. Until the end of follow-up Dec 31 st 2021, repeated measurements were performed for all parameters. Data analysis was performed using MD-Explorer (BioArtProducts, Rostock, Germany) and Python with multiple libraries. Linear regression models were applied in patients for DKK3, eGFR and UACR. Comparison of the models was performed with a twosided Kolmogorov-Smirnov test. Results: 1206 DKK3 measurements were performed in 1103 patients (621 male, age 70yrs, eGFR 29,41 ml/min/1.73qm, UACR 800 mg/g). 134 patients died during follow-up. DKK3 mean was 2905 pg/mg Cr (max. 20000, 75 % percentile 3800). 121 pts had DKK3 > 4000. At the end of follow-up 7 % of patients with DKK3 4000 (initial eGFR 15.7) underwent dialysis. Compared to eGFR and UACR at baseline, DKK3 > 4000 performed best to predict eGFR loss over the next 12 months. Conclusion: In this cohort of CKD patients, DKK3 > 4000 at baseline predicted the eGFR slope better than eGFR or UACR at baseline. DKK3 > 4000 reflected a higher risk of progression towards ESRD in patients with similar baseline eGFR levels

Supplemental Material for Kono et al., 2018

<div>Figure S1. Weighted pairwise similarity distribution for adjacent genes in B73 and PH207. Solid lines are from all pairs of adjacent genes in the genome and the dashed lines are from pairs of adjacent genes defined as tandem duplicates from raw CoGe output. Green line at 0.3 marks the threshold used to define tandem duplicate genes for downstream analysis.</div><div><br></div><div>Figure S2. Tandem duplicate gene cassette identification. Similarity heatmap on right shows an example tandem duplicate gene cassette in which the off-diagonal heat (yellow) shows high similarity among genes within the cassette. </div><div><br></div><div>Figure S3. Distribution of orthologous group sizes as defined by OrthoFinder. Grey box (size 10 to 75) indicates orthogroups that were used in downstream PAML analysis.</div><div><br></div><div>Figure S4. Example marked input tree for PAML relative rates analysis. Orthologous groups were defined using OrthoFinder.</div><div><br></div><div>Figure S5. Number of intervening genes in tandem duplicate gene cluster. Genes that are directly adjacent have an intervening gene number of zero.</div><div><br></div><div>Figure S6. Genomic locations of maize tandem duplicates for all chromosomes in B73. Purple ticks show tandem duplications. Black line shows gene density, dark grey line shows RNA transposable element density, light grey line shows DNA transposable elements per Mb. Subgenome 1 is shown in green shading and subgenome 2 is shown in blue shading.</div><div><br></div><div>Figure S7. Distance to nearest transposable element (upstream or downstream) for B73 tandem duplicate genes. </div><div><br></div><div>Table S1. Species, assembly versions, annotation versions, and data sources for the grass species used for orthologue identification.</div><div><br></div><div>Table S2. Summary of maize tandem duplicates in B73 and PH207. Cluster number is a generic number given to each tandem duplicate cluster. Duplicates in B73 are from the version 4 assembly and duplicates in PH207 are from the version 1 assembly. Shared duplicates are contained in the syntenic portion of both B73 and PH207 and private duplicates are in the syntenic portion of only one genome, and non-syntenic duplicates are in non co-orthologous blocks relative to rice and/or sorghum. Estimated date of tandem duplicates was determined based on substitution rates relative to sorghum.</div