Molecular evolution of glycinin and β-conglycinin gene families in soybean (Glycine max L. Merr.)

There are two main classes of multi-subunit seed storage proteins, glycinin (11S) and β-conglycinin (7S), which account for approximately 70% of the total protein in a typical soybean seed. The subunits of these two protein classes are encoded by a number of genes. The genomic organization of these genes follows a complex evolutionary history. This research was designed to describe the origin and maintenance of genes in each of these gene families by analyzing the synteny, phylogenies, selection pressure and duplications of the genes in each gene family. The ancestral glycinin gene initially experienced a tandem duplication event; then, the genome underwent two subsequent rounds of whole-genome duplication, thereby resulting in duplication of the glycinin genes, and finally a tandem duplication likely gave rise to the Gy1 and Gy2 genes. The β-conglycinin genes primarily originated through the more recent whole-genome duplication and several tandem duplications. Purifying selection has had a key role in the maintenance of genes in both gene families. In addition, positive selection in the glycinin genes and a large deletion in a β-conglycinin exon contribute to the diversity of the duplicate genes. In summary, our results suggest that the duplicated genes in both gene families prefer to retain similar function throughout evolution and therefore may contribute to phenotypic robustness.     

Evolution of the β-globin gene cluster in man and the primates

The arrangement of primate β-related globin genes has been determined by restriction endonuclease mapping of genomic DNA from species ranging from prosimians to man. The arrangement of the entire ?γγδβ-globin gene cluster in the gorilla and the yellow baboon is indistinguishable from that of man. Restriction site differences between these species are consistent with a surprisingly low overall rate of intergenic DNA sequence divergence of approximately 1% in 5 million years. A new world monkey (owl monkey) has a single γ-globin gene, suggesting that the ^Gγ-^Aγ-globin gene duplication in man is ancient, and occurred about 20 to 40 million years ago. The β-globin gene cluster in the brown lemur, a prosimian, is remarkably short (about 20,000 base-pairs) and contains single ?-, γ- and β-globin genes. The γ- and β-globin genes in this animal are separated by a curious gene containing the 3′ end of a β-globin gene preceded by sequences related to the 5′ end of the ?-globin gene.     

Susceptibility gene search for nephropathy and related traits in Mexican–Americans

The rising global epidemic of diabetic nephropathy (DN) will likely lead to increase in the prevalence of cardiovascular morbidity and mortality posing a serious burden for public health care. Despite greater understanding of the etiology of diabetes and the development of novel treatment strategies to control blood glucose levels, the prevalence and incidence rate of DN is increasing especially in minority populations including Mexican–Americans. Mexican–Americans with type 2 diabetes (T2DM) are three times more likely to develop microalbuminuria, and four times more likely to develop clinical proteinuria compared to non-Hispanic whites. Furthermore, Mexican–Americans have a sixfold increased risk of developing renal failure secondary to T2DM compared to Caucasians. Prevention and better treatment of DN should be a high priority for both health-care organizations and society at large. Pathogenesis of DN is multi-factorial. Familial clustering of DN-related traits in MAs show that DN and related traits are heritable and that genes play a susceptibility role. While, there has been some progress in identifying genes which when mutated influence an individual’s risk, major gene(s) responsible for DN are yet to be identified. Knowledge of the genetic causes of DN is essential for elucidation of its mechanisms, and for adequate classification, prognosis, and treatment. Self-identification and collaboration among researchers with suitable genomic and clinical data for meta-analyses in Mexican–Americans is critical for progress in replicating/identifying DN risk genes in this population. This paper reviews the approaches and recent efforts made to identify genetic variants contributing to risk for DN and related phenotypes in the Mexican–American population.     

Consistent isomiR expression patterns and 3′ addition events in miRNA gene clusters and families implicate functional and evolutionary relationships

3′ addition events in miRNAs are widely detected and may contribute to miRNA stability, but little is known about details of the events in miRNA gene clusters and families. Here, we performed a comprehensive analysis of isomiR expression patterns and 3′ additions in miRNA gene clusters and families by analyzing high-throughput sequencing dataset. According to dominant modified isomiRs, miRNA members in many miRNA gene clusters and families showed the same 3′ additional non-template nucleotides. Although clustered miRNAs and homologous miRNAs had consistent or inconsistent expression levels, we found many of them showed consistent expression patterns at isomiR levels. These findings revealed similar processing mechanism and 3′ modification event of miRNAs in gene clusters and families through miRNA maturation process. The consistent maturation mechanism may contribute to co-regulate biological processes, and may originate from ancestral miRNA genes through complex duplication history.     

Dynamic miRNA–mRNA paradigms: New faces of miRNAs

More and more evidences suggested that the flow of genetic information can be spatially and temporally regulated by non-coding RNAs (ncRNAs), such as microRNAs (miRNAs). Although biogenesis and function of miRNAs have been well detailed, elucidation of the dynamic interplays between miRNAs and mRNAs have just begun. Here, we highlighted that the miRNA–mRNA interactions which could take place in different cellular locations. During dynamic interactions, miRNA binding sites included not only 3′UTRs, but also 5′UTRs and CDSs. Under different physiological or pathological conditions, miRNAs could switch from translational inhibition to activation. Dynamic miRNA–mRNA paradigms which suggested a novel tip of the iceberg beneath the gene regulation network will provide clues for function studies of other ncRNAs.     

Genetic variability of the gene cluster CALHM1–3 in sporadic Creutzfeldt-Jakob disease

Perturbations of calcium homeostasis have been associated with several neurodegenerative disorders. A common polymorphism (rs2986017) in the CALHM1 gene, coding for a regulator of calcium homeostasis, is a genetic risk factor for the development of Alzheimer disease (AD). Although some authors failed to confirm these results, a meta-analysis has shown that this polymorphism modulates the age at disease onset. Furthermore, a recent association study has explored the genetic variability of CALHM1 gene and two adjacent paralog genes (CALHM3 and CALHM2) in an Asian population. Since several lines of evidence suggest that AD and prion diseases share pathophysiologic mechanisms, we investigated for the first time the genetic variability of the gene cluster formed by CALHM1 and its paralogs in a series of 235 sporadic Creutzfeldt-Jakob disease (sCJD) patients, and compared the genotypic and allelic frequencies with those presented in 329 controls from the same ancestry. As such, this work also represents the first association analysis of CALHM genes in sCJD. Sequencing analysis of the complete coding regions of the genes demonstrated the presence of 10 single nucleotide polymorphisms (SNP) within the CALHM genes. We observed that rs4918016-rs2986017-rs2986018 and rs41287502-rs41287500 polymorphic sites at CALHM1 were in linkage disequilibrium. We found marginal associations for sCJD risk at CALHM1 polymorphic sites rs41287502 and rs41287500 [coding for two linked missense mutations (p.(Met323Ile); (Gly282Cys)], and rs2986017 [p.(Leu86Pro)]. Interestingly, a TGG haplotype defined by the rs4918016-rs2986017-rs2986018 block was associated with sCJD. These findings underscore the need of future multinational collaborative initiatives in order to corroborate these seminal data.     

Genetic variability of the gene cluster CALHM1–3 in sporadic Creutzfeldt-Jakob disease

Perturbations of calcium homeostasis have been associated with several neurodegenerative disorders. A common polymorphism (rs2986017) in the CALHM1 gene, coding for a regulator of calcium homeostasis, is a genetic risk factor for the development of Alzheimer disease (AD). Although some authors failed to confirm these results, a meta-analysis has shown that this polymorphism modulates the age at disease onset. Furthermore, a recent association study has explored the genetic variability of CALHM1 gene and two adjacent paralog genes (CALHM3 and CALHM2) in an Asian population. Since several lines of evidence suggest that AD and prion diseases share pathophysiologic mechanisms, we investigated for the first time the genetic variability of the gene cluster formed by CALHM1 and its paralogs in a series of 235 sporadic Creutzfeldt-Jakob disease (sCJD) patients, and compared the genotypic and allelic frequencies with those presented in 329 controls from the same ancestry. As such, this work also represents the first association analysis of CALHM genes in sCJD. Sequencing analysis of the complete coding regions of the genes demonstrated the presence of 10 single nucleotide polymorphisms (SNP) within the CALHM genes. We observed that rs4918016-rs2986017-rs2986018 and rs41287502-rs41287500 polymorphic sites at CALHM1 were in linkage disequilibrium. We found marginal associations for sCJD risk at CALHM1 polymorphic sites rs41287502 and rs41287500 [coding for two linked missense mutations (p.(Met323Ile); (Gly282Cys)], and rs2986017 [p.(Leu86Pro)]. Interestingly, a TGG haplotype defined by the rs4918016-rs2986017-rs2986018 block was associated with sCJD. These findings underscore the need of future multinational collaborative initiatives in order to corroborate these seminal data.     

Gene–gene and gene–environment interactions in ulcerative colitis

Genome-wide association studies (GWAS) have identified at least 133 ulcerative colitis (UC) associated loci. The role of genetic factors in clinical practice is not clearly defined. The relevance of genetic variants to disease pathogenesis is still uncertain because of not characterized gene–gene and gene–environment interactions. We examined the predictive value of combining the 133 UC risk loci with genetic interactions in an ongoing inflammatory bowel disease (IBD) GWAS. The Wellcome Trust Case–Control Consortium (WTCCC) IBD GWAS was used as a replication cohort. We applied logic regression (LR), a novel adaptive regression methodology, to search for high-order interactions. Exploratory genotype correlations with UC sub-phenotypes [extent of disease, need of surgery, age of onset, extra-intestinal manifestations and primary sclerosing cholangitis (PSC)] were conducted. The combination of 133 UC loci yielded good UC risk predictability [area under the curve (AUC) of 0.86]. A higher cumulative allele score predicted higher UC risk. Through LR, several lines of evidence for genetic interactions were identified and successfully replicated in the WTCCC cohort. The genetic interactions combined with the gene-smoking interaction significantly improved predictability in the model (AUC, from 0.86 to 0.89, P = 3.26E?05). Explained UC variance increased from 37 to 42 % after adding the interaction terms. A within case analysis found suggested genetic association with PSC. Our study demonstrates that the LR methodology allows the identification and replication of high-order genetic interactions in UC GWAS datasets. UC risk can be predicted by a 133 loci and improved by adding gene–gene and gene–environment interactions.     

Comparison of theα-globin gene cluster structure in Perissodactyla

Summary To investigate molecular evolution in a mammalian order with a comprehensive fossil record, we have constructed-globin-like gene cluster maps for members of the order Perissodactyla. Although the arrangement of genes is the same in the five Equidae examined, the tapir and rhinoceros differ from each other and the horse in the position and number of their genes, but not in the arrangement of their and genes. In contrast to morphological work, a dendrogram derived from restriction site maps associates the tapir with the horse rather than with the rhinoceros; however, this phylogeny is not statistically significant. Among the Equidae,Equus caballus emerges as an outgroup, in agreement with data from other disciplines.     

Phylogenomic analyses of KCNA gene clusters in vertebrates: why do gene clusters stay intact?

Background  

Gene clusters are of interest for the understanding of genome evolution since they provide insight in large-scale duplications events as well as patterns of individual gene losses. Vertebrates tend to have multiple copies of gene clusters that typically are only single clusters or are not present at all in genomes of invertebrates. We investigated the genomic architecture and conserved non-coding sequences of vertebrate KCNA gene clusters. KCNA genes encode shaker-related voltage-gated potassium channels and are arranged in two three-gene clusters in tetrapods. Teleost fish are found to possess four clusters. The two tetrapod KNCA clusters are of approximately the same age as the Hox gene clusters that arose through duplications early in vertebrate evolution. For some genes, their conserved retention and arrangement in clusters are thought to be related to regulatory elements in the intergenic regions, which might prevent rearrangements and gene loss. Interestingly, this hypothesis does not appear to apply to the KCNA clusters, as too few conserved putative regulatory elements are retained.     

Why colour in subterranean vertebrates? Exploring the evolution of colour patterns in caecilian amphibians

The proximate functions of animal skin colour are difficult to assign as they can result from natural selection, sexual selection or neutral evolution under genetic drift. Most often colour patterns are thought to signal visual stimuli; so,their presence in subterranean taxa is perplexing. We evaluate the adaptive nature of colour patterns in nearly a third of all known species of caecilians, an order of amphibians most of which live in tropical soils and leaf litter. We found that certain colour pattern elements in caecilians can be explained based on characteristics concerning above-ground movement. Our study implies that certain caecilian colour patterns have convergently evolved under selection and we hypothesize their function most likely to be a synergy of aposematism and crypsis, related to periods when individuals move overground. In a wider context, our results suggest that very little exposure to daylight is required to evolve and maintain a varied array of colour patterns in animal skin.