A MicroRNA Linking Human Positive Selection and Metabolic Disorders

Wang, Lifeng; Sinnott-Armstrong, Nasa; Wagschal, Alexandre; Wark, Abigail R.; Camporez, João Paulo; Perry, Rachel J.; Ji, Fei; Sohn, Yoojin; Oh, Justin D.; Wu, Shi-Fang; Chery, Jessica; Moud, Bahareh Nemati; Saadat, Alham; Dankel, Simon N.; Mellgren, Gunnar; Tallapragada, Divya Sri Priyanka; Strobel, Sophie; Lee, Mi‐Jeong; Tewhey, Ryan; Sabeti, Pardis C.; Schaefer, Anne; Petri, Andreas; Kauppinen, Sakari; Chung, Raymond T.; Soukas, Alexander A.; Avruch, Joseph; Fried, Susan K.; Hauner, Hans; Sadreyev, Ruslan I.; Shulman, Gerald I.; Claussnitzer, Melina; Näär, Anders M.

doi:10.1016/j.cell.2020.09.017

Cited by 55 publications

(42 citation statements)

References 118 publications

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“…Therefore, the patient did not appear to have motor behaviors caused by miR‐128 abnormalities, suggesting the absence of significant alterations in the expression level of miR‐128. Recently, miR‐128‐1 has been shown a crucial metabolic regulator in mammals, controlling energy expenditure and contributing to metabolic disease (Wang et al, 2020). The fact that the presented patient had a normal body shape and a normal total cholesterol level was consistent with an expression level of miR‐128‐1 comparable to that of healthy controls without metabolic disease.…”

Section: Discussionmentioning

confidence: 99%

R3HDM1 haploinsufficiency is associated with mild intellectual disability

Fukushi

Inaba

Katoh

et al. 2021

American J of Med Genetics Pt A

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R3HDM1 (R3H domain containing 1) is an uncharacterized RNA‐binding protein that is highly expressed in the human cerebral cortex. We report the first case of a 12‐year‐old Japanese male with haploinsufficiency of R3HDM1. He presented with mild intellectual disability (ID) and developmental delay. He had a pericentric inversion of 46,XY,inv(2)(p16.1q21.3)dn with breakpoints in intron 19 of R3HDM1 (2q21.3) and the intergenic region (2p16.1). The R3HDM1 levels in his lymphoblastoid cells were reduced to approximately half that of the healthy controls. However, the expression of MIR128‐1, in intron 18 of R3HDM1, was not affected via the pericentric inversion. Knockdown of R3HDM1 in mouse embryonic hippocampal neurons suppressed dendritic growth and branching. Notably, the Database of Genomic Variants reported the case of a healthy control with a 488‐kb deletion that included both R3HDM1 and MIR128‐1. miR‐128 has been reported to inhibit dendritic growth and branching in mouse brain neurons, which directly opposes the novel functions of R3HDM1. These findings suggest that deleting both R3HDM1 and MIR128‐1 alleviates the symptoms of the disease caused by loss‐of‐function mutations in R3HDM1 only. Thus, haploinsufficiency of R3HDM1 in the patient may be the cause of the mild ID due to the genetic imbalance between R3HDM1 and MIR128‐1.

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Section: Discussionmentioning

confidence: 99%

R3HDM1 haploinsufficiency is associated with mild intellectual disability

Fukushi

Inaba

Katoh

et al. 2021

American J of Med Genetics Pt A

View full text Add to dashboard Cite

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“…Although the direct involvement of some miRNAs in the regulation of metabolism has been highlighted in many studies, the specific role as beneficial or detrimental modulators should be considered as complex and highly context-dependent. In this regard, in a recent paper, the role of miRNA-128-1 has been investigated, located at the center of a positively selected locus responsible of a thrifty phenotype [172]. In particular, an altered expression of this miRNA could have been beneficial in ancient times as adaptation to famine, but at the present, with overnutrition, it could predispose to obesity and type 2 diabetes.…”

Section: Nutrients As Epigenetic Modulators Of Health Span and Longevitymentioning

confidence: 99%

Nutrients and Pathways that Regulate Health Span and Life Span

et al. 2020

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Both life span and health span are influenced by genetic, environmental and lifestyle factors. With the genetic influence on human life span estimated to be about 20–25%, epigenetic changes play an important role in modulating individual health status and aging. Thus, a main part of life expectance and healthy aging is determined by dietary habits and nutritional factors. Excessive or restricted food consumption have direct effects on health status. Moreover, some dietary interventions including a reduced intake of dietary calories without malnutrition, or a restriction of specific dietary component may promote health benefits and decrease the incidence of aging-related comorbidities, thus representing intriguing potential approaches to improve healthy aging. However, the relationship between nutrition, health and aging is still not fully understood as well as the mechanisms by which nutrients and nutritional status may affect health span and longevity in model organisms. The broad effect of different nutritional conditions on health span and longevity occurs through multiple mechanisms that involve evolutionary conserved nutrient-sensing pathways in tissues and organs. These pathways interacting each other include the evolutionary conserved key regulators mammalian target of rapamycin, AMP-activated protein kinase, insulin/insulin-like growth factor 1 pathway and sirtuins. In this review we provide a summary of the main molecular mechanisms by which different nutritional conditions, i.e., specific nutrient abundance or restriction, may affect health span and life span.

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“…The evolution of Homo sapiens has been strongly shaped by positive selection in the last 100,000 years, by adapting to specific environments, diets, and cognitive challenges as populations expanded across the globe. Surviving such challenges has left remarkable footprints of selection in the human genome, like in the lactase ( LCT ) locus in European populations ( Bersaglieri et al, 2004 ; Wang et al, 2020 ), genes involved in skin pigmentation like MC1R ( John et al, 2003 ) or genes implicated in resistance to severe malaria infection like CD40L and G6PD ( Sabeti et al, 2002 ). Studying the evolutionary processes that resulted from these adaptations can uncover which path our ancestors travelled along to give rise to extant adaptations of present human populations.…”

Section: Introductionmentioning

confidence: 99%

Chromosome X-wide Analysis of Positive Selection in Human Populations: Common and Private Signals of Selection and its Impact on Inactivated Genes and Enhancers

et al. 2021

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The ability of detecting adaptive (positive) selection in the genome has opened the possibility of understanding the genetic basis of population-specific adaptations genome-wide. Here, we present the analysis of recent selective sweeps, specifically in the X chromosome, in human populations from the third phase of the 1,000 Genomes Project using three different haplotype-based statistics. We describe instances of recent positive selection that fit the criteria of hard or soft sweeps, and detect a higher number of events among sub-Saharan Africans than non-Africans (Europe and East Asia). A global enrichment of neural-related processes is observed and numerous genes related to fertility appear among the top candidates, reflecting the importance of reproduction in human evolution. Commonalities with previously reported genes under positive selection are found, while particularly strong new signals are reported in specific populations or shared across different continental groups. We report an enrichment of signals in genes that escape X chromosome inactivation, which may contribute to the differentiation between sexes. We also provide evidence of a widespread presence of soft-sweep-like signatures across the chromosome and a global enrichment of highly scoring regions that overlap potential regulatory elements. Among these, enhancers-like signatures seem to present putative signals of positive selection which might be in concordance with selection in their target genes. Also, particularly strong signals appear in regulatory regions that show differential activities, which might point to population-specific regulatory adaptations.

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A MicroRNA Linking Human Positive Selection and Metabolic Disorders

Cited by 55 publications

References 118 publications

R3HDM1 haploinsufficiency is associated with mild intellectual disability

R3HDM1 haploinsufficiency is associated with mild intellectual disability

Nutrients and Pathways that Regulate Health Span and Life Span

Chromosome X-wide Analysis of Positive Selection in Human Populations: Common and Private Signals of Selection and its Impact on Inactivated Genes and Enhancers

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