scholarly journals Pervasive Selection against MicroRNA Target Sites in Human Populations

2020 ◽  
Vol 37 (12) ◽  
pp. 3399-3408
Author(s):  
Andrea Hatlen ◽  
Antonio Marco
Keyword(s):  
Population Differentiation ◽  
Purifying Selection ◽  
Human Populations ◽  
Nucleotide Polymorphisms ◽  
Microrna Target ◽  
Single Nucleotide ◽  
Target Sites ◽  
Statistical Support ◽  
Novel Target ◽  
New Alleles

Abstract MicroRNA target sites are often conserved during evolution and purifying selection to maintain such sites is expected. On the other hand, comparative analyses identified a paucity of microRNA target sites in coexpressed transcripts, and novel target sites can potentially be deleterious. We proposed that selection against novel target sites pervasive. The analysis of derived allele frequencies revealed that, when the derived allele is a target site, the proportion of nontarget sites is higher than expected, particularly for highly expressed microRNAs. Thus, new alleles generating novel microRNA target sites can be deleterious and selected against. When we analyzed ancestral target sites, the derived (nontarget) allele frequency does not show statistical support for microRNA target allele conservation. We investigated the joint effects of microRNA conservation and expression and found that selection against microRNA target sites depends mostly on the expression level of the microRNA. We identified microRNA target sites with relatively high levels of population differentiation. However, when we analyze separately target sites in which the target allele is ancestral to the population, the proportion of single-nucleotide polymorphisms with high Fst significantly increases. These findings support that population differentiation is more likely in target sites that are lost than in the gain of new target sites. Our results indicate that selection against novel microRNA target sites is prevalent and, although individual sites may have a weak selective pressure, the overall effect across untranslated regions is not negligible and should be accounted when studying the evolution of genomic sequences.

scholarly journals Pervasive selection against microRNA target sites in human populations

2018 ◽  
Author(s):  
Andrea Hatlen ◽  
Antonio Marco
Keyword(s):  
Population Differentiation ◽  
Selective Pressure ◽  
Purifying Selection ◽  
Untranslated Regions ◽  
Human Populations ◽  
Microrna Target ◽  
Target Sites ◽  
Statistical Support ◽  
Novel Target ◽  
New Alleles

ABSTRACTMicroRNA target sites are often conserved during evolution and purifying selection to maintain such sites is expected. On the other hand, comparative analyses identified a paucity of microRNA target sites in co-expressed transcripts, and novel target sites can potentially be deleterious. We proposed that selection against novel target sites pervasive. The analysis of derived allele frequencies revealed that, when the derived allele is a target site, the proportion of non-target sites is higher than expected, particularly for highly expressed microRNAs. Thus, new alleles generating novel microRNA target sites can be deleterious and selected against. When we analysed ancestral target sites the derived (non-target) allele frequency does not show statistical support for microRNA target allele conservation. We investigated the joint effects of microRNA conservation and expression and found that selection against microRNA target sites depends mostly on the expression level of the microRNA. We identified microRNA target sites with relatively high levels of population differentiation. However, when we analyse separately target sites in which the target allele is ancestral to the population, the proportion of SNPs with high Fst significantly increases. These findings support population differentiation is more likely in target sites that are lost than in the gain of new target sites. Our results indicate that selection against novel microRNA target sites is prevalent and, although individual sites may have a weak selective pressure, the overall effect across untranslated regions is not negligible and should be accounted when studying the evolution of genomic sequences.

scholarly journals Single-Nucleotide Polymorphisms Inside MicroRNA Target Sites Influence Tumor Susceptibility

2010 ◽  
Vol 70 (7) ◽  
pp. 2789-2798 ◽  
Author(s):  
Milena S. Nicoloso ◽  
Hao Sun ◽  
Riccardo Spizzo ◽  
Hyunsoo Kim ◽  
Priyankara Wickramasinghe ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Microrna Target ◽  
Single Nucleotide ◽  
Tumor Susceptibility ◽  
Target Sites

scholarly journals Single-nucleotide polymorphisms inside microRNA target sites influence the susceptibility to type 2 diabetes

2013 ◽  
Vol 58 (3) ◽  
pp. 135-141 ◽  
Author(s):  
Xu Zhao ◽  
Qing Ye ◽  
Kang Xu ◽  
Jinluo Cheng ◽  
Yanqin Gao ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Single Nucleotide Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Microrna Target ◽  
Single Nucleotide ◽  
Target Sites

scholarly journals PopTargs: a database for studying population evolutionary genetics of human microRNA target sites

Database ◽  
2019 ◽  
Vol 2019 ◽  
Author(s):  
Andrea Hatlen ◽  
Mohab Helmy ◽  
Antonio Marco
Keyword(s):  
Evolutionary Genetics ◽  
Human Populations ◽  
Microrna Target ◽  
Multiple Sources ◽  
Web Based ◽  
Regulatory Motifs ◽  
Multiple Datasets ◽  
Custom Made ◽  
Target Sites ◽  
Selective Forces

Abstract There is an increasing interest in the study of polymorphic variants at gene regulatory motifs, including microRNA target sites. Understanding the effects of selective forces at specific microRNA target sites, together with other factors like expression levels or evolutionary conservation, requires the joint study of multiple datasets. We have compiled information from multiple sources and compared it with predicted microRNA target sites to build a comprehensive database for the study of microRNA targets in human populations. PopTargs is a web-based tool that allows the easy extraction of multiple datasets and the joint analyses of them, including allele frequencies, ancestral status, population differentiation statistics and site conservation. The user can also compare the allele frequency spectrum between two groups of target sites and conveniently produce plots. The database can be easily expanded as new data becomes available and the raw database as well as code for creating new custom-made databases is available for downloading. We also describe a few illustrative examples.

scholarly journals Genetics of Lactose Intolerance: An Updated Review and Online Interactive World Maps of Phenotype and Genotype Frequencies

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2689
Author(s):  
Augusto Anguita-Ruiz ◽  
Concepción M. Aguilera ◽  
Ángel Gil
Keyword(s):  
Genetic Basis ◽  
Human Populations ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genotype Frequencies ◽  
Genetic Mechanisms ◽  
Visualization Tools ◽  
Available Information ◽  
Static World ◽  
Interactive Resources

In humans the ability to digest milk lactose is conferred by a β-galactosidase enzyme called lactase-phlorizin hydrolase (LPH). While in some humans (approximately two-thirds of humankind) the levels of this enzyme decline drastically after the weaning phase (a trait known as lactase non-persistence (LNP)), some other individuals are capable of maintaining high levels of LPH lifelong (lactase persistence (LP)), thus being able to digest milk during adulthood. Both lactase phenotypes in humans present a complex genetic basis and have been widely investigated during the last decades. The distribution of lactase phenotypes and their associated single nucleotide polymorphisms (SNPs) across human populations has also been extensively studied, though not recently reviewed. All available information has always been presented in the form of static world maps or large dimension tables, so that it would benefit from the newly available visualization tools, such as interactive world maps. Taking all this into consideration, the aims of the present review were: (1) to gather and summarize all available information on LNP and LP genetic mechanisms and evolutionary adaptation theories, and (2) to create online interactive world maps, including all LP phenotype and genotype frequency data reported to date. As a result, we have created two online interactive resources, which constitute an upgrade over previously published static world maps, and allow users a personalized data exploration, while at the same time accessing complete reports by population or ethnicity.

scholarly journals Mobile introns shape the genetic diversity of their host genes

2016 ◽  
Author(s):  
Jelena Repar ◽  
Tobias Warnecke
Keyword(s):  
Genetic Diversity ◽  
Gene Diversity ◽  
Plant Mitochondria ◽  
Purifying Selection ◽  
Nucleotide Polymorphisms ◽  
Co Conversion ◽  
Target Sites ◽  
Random Patterns ◽  
Empty Target ◽  
Self Splicing

AbstractSelf-splicing introns populate several highly conserved protein-coding genes in fungal and plant mitochondria. In fungi, many of these introns have retained their ability to spread to intron-free target sites, often assisted by intron-encoded endonucleases that initiate the homing process. Here, leveraging population genomic data from Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Lachancea kluyveri, we expose non-random patterns of genetic diversity in exons that border self-splicing introns. In particular, we show that, in all three species, the density of single nucleotide polymorphisms increases as one approaches a mobile intron. Through multiple lines of evidence we rule out relaxed purifying selection as the cause of uneven nucleotide diversity. Instead, our findings implicate intron mobility as a direct driver of host gene diversity. We discuss two mechanistic scenarios that are consistent with the data: either endonuclease activity and subsequent error-prone repair have left a mutational footprint on the insertion environment of mobile introns or non-random patterns of genetic diversity are caused by exonic co-conversion, which occurs when introns spread to empty target sites via homologous recombination. Importantly, however, we show that exonic co-conversion can only explain diversity gradients near intron-exon boundaries if the conversion templates comes from outside the population. In other words, there must be pervasive and ongoing horizontal gene transfer of self-splicing introns into extant fungal populations.

scholarly journals Population Differentiation at the HLA Genes

2017 ◽  
Author(s):  
Débora Y. C. Brandt ◽  
Jônatas César ◽  
Jérôme Goudet ◽  
Diogo Meyer
Keyword(s):  
Population Differentiation ◽  
Balancing Selection ◽  
Global Scale ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Hla Genes ◽  
Genome Wide ◽  
Different Populations ◽  
Genomic Regions

ABSTRACTBalancing selection is defined as a class of selective regimes that maintain polymorphism above what is expected under neutrality. Theory predicts that balancing selection reduces population differentiation, as measured by FST. However, balancing selection regimes in which different sets of alleles are maintained in different populations could increase population differentiation. To tackle this issue, we investigated population differentiation at the HLA genes, which constitute the most striking example of balancing selection in humans. We found that population differentiation of single nucleotide polymorphisms (SNPs) at the HLA genes is on average lower than that of SNPs in other genomic regions. However, this result depends on accounting for the differences in allele frequency between selected and putatively neutral sites. Our finding of reduced differentiation at SNPs within HLA genes suggests a predominant role of shared selective pressures among populations at a global scale. However, in pairs of closely related populations, where genome-wide differentiation is low, differentiation at HLA is higher than in other genomic regions. This pattern was reproduced in simulations of overdominant selection. We conclude that population differentiation at the HLA genes is generally lower than genome-wide, but it may be higher for recently diverged population pairs, and that this pattern can be explained by a simple overdominance regime.

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