scholarly journals Genes Associated with SLE Are Targets of Recent Positive Selection

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Paula S. Ramos ◽  
Stephanie R. Shaftman ◽  
Ralph C. Ward ◽  
Carl D. Langefeld
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Lupus Erythematosus ◽  
Genetic Basis ◽  
Ethnic Disparities ◽  
Future Research ◽  
Risk Alleles ◽  
Recent Positive Selection ◽  
Risk Variants ◽  
Genomic Regions

The reasons for the ethnic disparities in the prevalence of systemic lupus erythematosus (SLE) and the relative high frequency of SLE risk alleles in the population are not fully understood. Population genetic factors such as natural selection alter allele frequencies over generations and may help explain the persistence of such common risk variants in the population and the differential risk of SLE. In order to better understand the genetic basis of SLE that might be due to natural selection, a total of 74 genomic regions with compelling evidence for association with SLE were tested for evidence of recent positive selection in the HapMap and HGDP populations, using population differentiation, allele frequency, and haplotype-based tests. Consistent signs of positive selection across different studies and statistical methods were observed at several SLE-associated loci, includingPTPN22,TNFSF4,TET3-DGUOK,TNIP1,UHRF1BP1,BLK, andITGAMgenes. This study is the first to evaluate and report that several SLE-associated regions show signs of positive natural selection. These results provide corroborating evidence in support of recent positive selection as one mechanism underlying the elevated population frequency of SLE risk loci and supports future research that integrates signals of natural selection to help identify functional SLE risk alleles.

scholarly journals Positive selection and fast turnover rate in tumor suppressor genes reveal how cetaceans resist cancer

2020 ◽  
Author(s):  
Daniela Tejada-Martinez ◽  
João Pedro de Magalhães ◽  
Juan C. Opazo
Keyword(s):  
Natural Selection ◽  
Tumor Suppressor ◽  
Positive Selection ◽  
Tumor Suppressor Genes ◽  
Turnover Rate ◽  
Genetic Basis ◽  
Large Body ◽  
Nijmegen Breakage Syndrome ◽  
Chromosome Break ◽  
Suppressor Genes

AbstractCetaceans are the longest-lived species of mammals and the largest in the history of the planet. They have developed mechanisms against diseases like cancer, however their underlying molecular and genetic basis remain unknown. The goal of this study was to investigate the role of natural selection in the evolution of tumor suppressor genes in cetaceans. We found signal of positive selection 29 tumor suppressor genes and duplications in 197 genes. The turnover rate of tumor suppressor genes was almost 6 times faster in cetaceans when compared to other mammals. Those genes with duplications and with positive selection are involved in important cancer regulation mechanisms (e.g. chromosome break, DNA repair and biosynthesis of fatty acids). They are also related with multiple ageing and neurological disorders in humans (e.g. Alzheimer, Nijmegen breakage syndrome, and schizophrenia). These results provide evolutionary evidence that natural selection in tumor suppressor genes could act on species with large body sizes and extended life span, providing insights into the genetic basis of disease resistance. We propose that the cetaceans are an important model in cancer, ageing and neuronal, motor and behavior disorders.

scholarly journals The Evolutionary Persistence of Genes That Increase Mental Disorders Risk

2008 ◽  
Vol 17 (6) ◽  
pp. 395-399 ◽  
Author(s):  
Matthew C. Keller
Keyword(s):  
Natural Selection ◽  
Mental Disorders ◽  
Evolutionary Genetics ◽  
Future Research ◽  
Human Populations ◽  
Psychiatric Genetics ◽  
Severe Mental Disorders ◽  
Risk Alleles ◽  
Deleterious Alleles ◽  
Evolutionary Persistence

Natural selection constantly removes those genetic variants (alleles) that even slightly decrease average reproductive success. Yet, given the high heritabilities and prevalence rates of severe mental disorders, human populations seem to be awash in deleterious alleles. Evolutionary genetics offers an illuminating framework for understanding why mental disorder risk alleles have persisted despite natural selection, and this framework can help guide future research in behavioral and psychiatric genetics.

scholarly journals Genome-wide scans for signatures of selection in Mangalarga Marchador horses using high-throughput SNP genotyping

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wellington B. Santos ◽  
Gustavo P. Schettini ◽  
Amanda M. Maiorano ◽  
Fernando O. Bussiman ◽  
Júlio C. C. Balieiro ◽  
...  
Keyword(s):  
Positive Selection ◽  
Candidate Genes ◽  
Limb Development ◽  
Balancing Selection ◽  
Phenotypic Traits ◽  
Nadh Regeneration ◽  
Recent Positive Selection ◽  
Signatures Of Selection ◽  
Genomic Regions ◽  
Tajima’S D

Abstract Background The detection of signatures of selection in genomic regions provides insights into the evolutionary process, enabling discoveries regarding complex phenotypic traits. In this research, we focused on identifying genomic regions affected by different selection pressures, mainly highlighting the recent positive selection, as well as understanding the candidate genes and functional pathways associated with the signatures of selection in the Mangalarga Marchador genome. Besides, we seek to direct the discussion about genes and traits of importance in this breed, especially traits related to the type and quality of gait, temperament, conformation, and locomotor system. Results Three different methods were used to search for signals of selection: Tajima’s D (TD), the integrated haplotype score (iHS), and runs of homozygosity (ROH). The samples were composed of males (n = 62) and females (n = 130) that were initially chosen considering well-defined phenotypes for gait: picada (n = 86) and batida (n = 106). All horses were genotyped using a 670 k Axiom® Equine Genotyping Array​ (Axiom MNEC670). In total, 27, 104 (chosen), and 38 candidate genes were observed within the signatures of selection identified in TD, iHS, and ROH analyses, respectively. The genes are acting in essential biological processes. The enrichment analysis highlighted the following functions: anterior/posterior pattern for the set of genes (GLI3, HOXC9, HOXC6, HOXC5, HOXC4, HOXC13, HOXC11, and HOXC10); limb morphogenesis, skeletal system, proximal/distal pattern formation, JUN kinase activity (CCL19 and MAP3K6); and muscle stretch response (MAPK14). Other candidate genes were associated with energy metabolism, bronchodilator response, NADH regeneration, reproduction, keratinization, and the immunological system. Conclusions Our findings revealed evidence of signatures of selection in the MM breed that encompass genes acting on athletic performance, limb development, and energy to muscle activity, with the particular involvement of the HOX family genes. The genome of MM is marked by recent positive selection. However, Tajima’s D and iHS results point also to the presence of balancing selection in specific regions of the genome.

scholarly journals Detecting ancient positive selection in humans using extended lineage sorting

2016 ◽  
Author(s):  
Stéphane Peyrégne ◽  
Michael James Boyle ◽  
Michael Dannemann ◽  
Kay Prüfer
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Molecular Basis ◽  
Neutral Evolution ◽  
Selective Sweeps ◽  
Lineage Sorting ◽  
1000 Genomes ◽  
Regulatory Changes ◽  
Genomic Regions ◽  
Human Specific

ABSTRACTNatural selection that affected modern humans early in their evolution has likely shaped some of the traits that set present-day humans apart from their closest extinct and living relatives. The ability to detect ancient natural selection in the human genome could provide insights into the molecular basis for these human-specific traits. Here, we introduce a method for detecting ancient selective sweeps by scanning for extended genomic regions where our closest extinct relatives, Neandertals and Denisovans, fall outside of the present-day human variation. Regions that are unusually long indicate the presence of lineages that reached fixation in the human population faster than expected under neutral evolution. Using simulations we show that the method is able to detect ancient events of positive selection and that it can differentiate those from background selection. Applying our method to the 1000 Genomes dataset, we find evidence for ancient selective sweeps favoring regulatory changes and present a list of genomic regions that are predicted to underlie positively selected human specific traits.

scholarly journals No Evidence for Widespread Positive Selection Signatures in Common Risk Alleles Associated with Schizophrenia

2019 ◽  
Vol 46 (3) ◽  
pp. 603-611
Author(s):  
Yao Yao ◽  
Jia Yang ◽  
Yimin Xie ◽  
Hai Liao ◽  
Baoying Yang ◽  
...  
Keyword(s):  
Positive Selection ◽  
Nucleotide Polymorphisms ◽  
Human Beings ◽  
Single Nucleotide ◽  
Selection Theory ◽  
Fitness Effects ◽  
Protective Allele ◽  
Risk Alleles ◽  
Recent Positive Selection ◽  
Negative Controls

Abstract Schizophrenia poses an evolutionary-genetic paradox as it exhibits strongly negative fitness effects (early mortality and decreased fecundity), yet it persists at a prevalence of approximately 1% worldwide. Evidence from several studies have suggested that schizophrenia is evolved and maintained in part as a maladaptive byproduct of recent positive selection and adaptive evolution in human beings. However, inconsistent results have been also proposed, challenging the recent positive selection theory to explain the high population frequency of schizophrenia-associated alleles. Here, we used public domain data to locate signatures of positive selection based on genetic diversity, derived allele frequency, differentiation between populations, and long haplotypes at schizophrenia-associated single nucleotide polymorphisms (SNPs) and randomly selected SNPs (as negative controls). We found evidence for positive selection at 10 out of the 105 schizophrenia-associated SNPs, while 5 of these SNPs involved positive selection for the protective allele. Taken together, the absence of widespread positive selection signals at the schizophrenia-associated SNPs, along with the fact that half of the positive selection favored the protective allele, provide little evidence supporting the positive selection theory in schizophrenia.

scholarly journals Effects of linked selective sweeps on demographic inference and model selection

2016 ◽  
Author(s):  
Daniel R. Schrider ◽  
Alexander G. Shanku ◽  
Andrew D. Kern
Keyword(s):  
Genetic Variation ◽  
Natural Selection ◽  
Positive Selection ◽  
Population Size ◽  
Natural Populations ◽  
Parameter Estimates ◽  
Selective Sweeps ◽  
Recent Positive Selection ◽  
Demographic Inference ◽  
The Impact

AbstractThe availability of large-scale population genomic sequence data has resulted in an explosion in efforts to infer the demographic histories of natural populations across a broad range of organisms. As demographic events alter coalescent genealogies they leave detectable signatures in patterns of genetic variation within and between populations. Accordingly, a variety of approaches have been designed to leverage population genetic data to uncover the footprints of demographic change in the genome. The vast majority of these methods make the simplifying assumption that the measures of genetic variation used as their input are unaffected by natural selection. However, natural selection can dramatically skew patterns of variation not only at selected sites, but at linked, neutral loci as well. Here we assess the impact of recent positive selection on demographic inference by characterizing the performance of three popular methods through extensive simulation of datasets with varying numbers of linked selective sweeps. In particular, we examined three different demographic models relevant to a number of species, finding that positive selection can bias parameter estimates of each of these models—often severely. Moreover, we find that selection can lead to incorrect inferences of population size changes when none have occurred. We argue that the amount of recent positive selection required to skew inferences may often be acting in natural populations. These results suggest that demographic studies conducted in many species to date may have exaggerated the extent and frequency of population size changes.

scholarly journals Common Risk Alleles for Inflammatory Diseases Are Targets of Recent Positive Selection

2013 ◽  
Vol 92 (4) ◽  
pp. 517-529 ◽  
Author(s):  
Towfique Raj ◽  
Manik Kuchroo ◽  
Joseph M. Replogle ◽  
Soumya Raychaudhuri ◽  
Barbara E. Stranger ◽  
...  
Keyword(s):  
Positive Selection ◽  
Inflammatory Diseases ◽  
Risk Alleles ◽  
Recent Positive Selection

scholarly journals Positive natural selection in primate genes of the type I interferon response

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Elena N. Judd ◽  
Alison R. Gilchrist ◽  
Nicholas R. Meyerson ◽  
Sara L. Sawyer
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Type I Interferon ◽  
Interferon Response ◽  
Type I ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Multiple Sequence Alignments ◽  
Interferon Stimulated Genes ◽  
Interferon Induction

Abstract Background The Type I interferon response is an important first-line defense against viruses. In turn, viruses antagonize (i.e., degrade, mis-localize, etc.) many proteins in interferon pathways. Thus, hosts and viruses are locked in an evolutionary arms race for dominance of the Type I interferon pathway. As a result, many genes in interferon pathways have experienced positive natural selection in favor of new allelic forms that can better recognize viruses or escape viral antagonists. Here, we performed a holistic analysis of selective pressures acting on genes in the Type I interferon family. We initially hypothesized that the genes responsible for inducing the production of interferon would be antagonized more heavily by viruses than genes that are turned on as a result of interferon. Our logic was that viruses would have greater effect if they worked upstream of the production of interferon molecules because, once interferon is produced, hundreds of interferon-stimulated proteins would activate and the virus would need to counteract them one-by-one. Results We curated multiple sequence alignments of primate orthologs for 131 genes active in interferon production and signaling (herein, “induction” genes), 100 interferon-stimulated genes, and 100 randomly chosen genes. We analyzed each multiple sequence alignment for the signatures of recurrent positive selection. Counter to our hypothesis, we found the interferon-stimulated genes, and not interferon induction genes, are evolving significantly more rapidly than a random set of genes. Interferon induction genes evolve in a way that is indistinguishable from a matched set of random genes (22% and 18% of genes bear signatures of positive selection, respectively). In contrast, interferon-stimulated genes evolve differently, with 33% of genes evolving under positive selection and containing a significantly higher fraction of codons that have experienced selection for recurrent replacement of the encoded amino acid. Conclusion Viruses may antagonize individual products of the interferon response more often than trying to neutralize the system altogether.

scholarly journals The Genetic Basis of Hypertriglyceridemia

2021 ◽  
Vol 23 (8) ◽  
Author(s):  
Germán D. Carrasquilla ◽  
Malene Revsbech Christiansen ◽  
Tuomas O. Kilpeläinen
Keyword(s):  
Genetic Basis ◽  
Association Studies ◽  
Cumulative Effect ◽  
Genome Wide Association Studies ◽  
Genetic Loci ◽  
Risk Variants ◽  
Genome Wide ◽  
Severe Hypertriglyceridemia ◽  
Increased Risk ◽  
Polygenic Scores

Abstract Purpose of Review Hypertriglyceridemia is a common dyslipidemia associated with an increased risk of cardiovascular disease and pancreatitis. Severe hypertriglyceridemia may sometimes be a monogenic condition. However, in the vast majority of patients, hypertriglyceridemia is due to the cumulative effect of multiple genetic risk variants along with lifestyle factors, medications, and disease conditions that elevate triglyceride levels. In this review, we will summarize recent progress in the understanding of the genetic basis of hypertriglyceridemia. Recent Findings More than 300 genetic loci have been identified for association with triglyceride levels in large genome-wide association studies. Studies combining the loci into polygenic scores have demonstrated that some hypertriglyceridemia phenotypes previously attributed to monogenic inheritance have a polygenic basis. The new genetic discoveries have opened avenues for the development of more effective triglyceride-lowering treatments and raised interest towards genetic screening and tailored treatments against hypertriglyceridemia. Summary The discovery of multiple genetic loci associated with elevated triglyceride levels has led to improved understanding of the genetic basis of hypertriglyceridemia and opened new translational opportunities.

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