Examination of signatures of recent positive selection on genes involved in human sialic acid biology

AbstractSialic acids are nine carbon sugars ubiquitously found on the surfaces of vertebrate cells and are involved in various immune response-related processes. In humans, at least 58 genes spanning diverse functions, from biosynthesis and activation to recycling and degradation, are involved in sialic acid biology. Because of their role in immunity, sialic acid biology genes have been hypothesized to exhibit elevated rates of evolutionary change. Consistent with this hypothesis, several genes involved in sialic acid biology have experienced higher rates of non-synonymous substitutions in the human lineage than their counterparts in other great apes, perhaps in response to ancient pathogens that infected hominins millions of years ago (paleopathogens). To test whether sialic acid biology genes have also experienced more recent positive selection during the evolution of the modern human lineage, reflecting adaptation to contemporary cosmopolitan or geographically-restricted pathogens, we examined whether their protein-coding regions showed evidence of recent hard and soft selective sweeps. This examination involved the calculation of four measures that quantify changes in allele frequency spectra, extent of population differentiation, and haplotype homozygosity caused by recent hard and soft selective sweeps for 55 sialic acid biology genes using publicly available whole genome sequencing data from 1,668 humans from three ethnic groups. To disentangle evidence for selection from confounding demographic effects, we compared the observed patterns in sialic acid biology genes to simulated sequences of the same length under a model of neutral evolution that takes into account human demographic history. We found that the patterns of genetic variation of most sialic acid biology genes did not significantly deviate from neutral expectations and were not significantly different among genes belonging to different functional categories. Those few sialic acid biology genes that significantly deviated from neutrality either experienced soft sweeps or population-specific hard sweeps. Interestingly, while most hard sweeps occurred on genes involved in sialic acid recognition, most soft sweeps involved genes associated with recycling, degradation and activation, transport, and transfer functions. We propose that the lack of signatures of recent positive selection for the majority of the sialic acid biology genes is consistent with the view that these genes regulate immune responses against ancient rather than contemporary cosmopolitan or geographically restricted pathogens.

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Examination of Signatures of Recent Positive Selection on Genes Involved in Human Sialic Acid Biology

G3 Genes|Genome|Genetics ◽

10.1534/g3.118.200035 ◽

2018 ◽

Vol 8 (4) ◽

pp. 1315-1325 ◽

Cited By ~ 4

Author(s):

Jiyun M. Moon ◽

David M. Aronoff ◽

John A. Capra ◽

Patrick Abbot ◽

Antonis Rokas

Keyword(s):

Sialic Acid ◽

Positive Selection ◽

Recent Positive Selection

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Population Differentiation as an Indicator of Recent Positive Selection in Humans: An Empirical Evaluation

Genetics ◽

10.1534/genetics.109.107722 ◽

2009 ◽

Vol 183 (3) ◽

pp. 1065-1077 ◽

Cited By ~ 33

Author(s):

Yali Xue ◽

Xuelong Zhang ◽

Ni Huang ◽

Allan Daly ◽

Christopher J. Gillson ◽

...

Keyword(s):

Positive Selection ◽

Population Differentiation ◽

Empirical Evaluation ◽

High Population ◽

Data Sets ◽

Extended Haplotype ◽

Frequency Spectra ◽

Significance Threshold ◽

Recent Positive Selection ◽

Extended Haplotypes

We have evaluated the extent to which SNPs identified by genomewide surveys as showing unusually high levels of population differentiation in humans have experienced recent positive selection, starting from a set of 32 nonsynonymous SNPs in 27 genes highlighted by the HapMap1 project. These SNPs were genotyped again in the HapMap samples and in the Human Genome Diversity Project–Centre d'Etude du Polymorphisme Humain (HGDP–CEPH) panel of 52 populations representing worldwide diversity; extended haplotype homozygosity was investigated around all of them, and full resequence data were examined for 9 genes (5 from public sources and 4 from new data sets). For 7 of the genes, genotyping errors were responsible for an artifactual signal of high population differentiation and for 2, the population differentiation did not exceed our significance threshold. For the 18 genes with confirmed high population differentiation, 3 showed evidence of positive selection as measured by unusually extended haplotypes within a population, and 7 more did in between-population analyses. The 9 genes with resequence data included 7 with high population differentiation, and 5 showed evidence of positive selection on the haplotype carrying the nonsynonymous SNP from skewed allele frequency spectra; in addition, 2 showed evidence of positive selection on unrelated haplotypes. Thus, in humans, high population differentiation is (apart from technical artifacts) an effective way of enriching for recently selected genes, but is not an infallible pointer to recent positive selection supported by other lines of evidence.

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On the unfounded enthusiasm for soft selective sweeps II: examining recent evidence from humans, flies, and viruses

10.1101/443051 ◽

2018 ◽

Author(s):

Rebecca B. Harris ◽

Andrew Sackman ◽

Jeffrey D. Jensen

Keyword(s):

Positive Selection ◽

Large Scale ◽

Natural Populations ◽

Population Data ◽

Population Level ◽

Selective Sweeps ◽

Effective Population ◽

Initial Description ◽

Neutral Models ◽

Soft Selective Sweeps

ABSTRACTSince the initial description of the genomic patterns expected under models of positive selection acting on standing genetic variation and on multiple beneficial mutations—so-called soft selective sweeps—researchers have sought to identify these patterns in natural population data. Indeed, over the past two years, large-scale data analyses have argued that soft sweeps are pervasive across organisms of very different effective population size and mutation rate—humans, Drosophila, and HIV. Yet, others have evaluated the relevance of these models to natural populations, as well as the identifiability of the models relative to other known population-level processes, arguing that soft sweeps are likely to be rare. Here, we look to reconcile these opposing results by carefully evaluating three recent studies and their underlying methodologies. Using population genetic theory, as well as extensive simulation, we find that all three examples are prone to extremely high false-positive rates, incorrectly identifying soft sweeps under both hard sweep and neutral models. Furthermore, we demonstrate that well-fit demographic histories combined with rare hard sweeps serve as the more parsimonious explanation. These findings represent a necessary response to the growing tendency of invoking parameter-heavy, assumption-laden models of pervasive positive selection, and neglecting best practices regarding the construction of proper demographic null models.

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Detecting ancient positive selection in humans using extended lineage sorting

10.1101/092999 ◽

2016 ◽

Cited By ~ 1

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.

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Effects of linked selective sweeps on demographic inference and model selection

10.1101/047019 ◽

2016 ◽

Cited By ~ 2

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.

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Local and temporal adaptation to climatic change in a wild tomato species via selective sweeps.

10.1101/2021.09.24.461657 ◽

2021 ◽

Author(s):

Kai Wei ◽

Gustavo Adolfo Silva Arias ◽

Aurelien Tellier

Keyword(s):

Positive Selection ◽

Local Adaptation ◽

Demographic History ◽

Regulatory Gene ◽

Ecological Niches ◽

Selective Sweeps ◽

Wild Tomato ◽

Wild Tomato Species ◽

Tomato Species ◽

Adaptive Processes

Positive Darwinian selection is the driving force underpinning local (in space) and temporal (in time) adaptation, and leaves footprints of selective sweeps at the underlying major genes. These two adaptive processes are classically considered independently, so that most genomic selection scans uncover only recent sweeps underpinning spatial adaptation. However, understanding if these adaptive processes are intermingled and share common genetic bases is crucial to predict a species evolutionary potential, for example in response to changing environmental conditions. We use whole genome data from six populations across three different habitats of the wild tomato species Solanum chilense, to 1) infer the past demographic history, and 2) search for genes under strong positive selection. We then correlate the demographic history, allele frequencies in space and time, the age of selection events and the reconstructed historical ecological distribution of the species over five main climatic periods spanning 150,000 years. We find evidence for several selective sweeps targeting regulatory networks involved in root hair development in low altitude, and response to photoperiod and vernalization in high altitude populations. These sweeps occur in a concerted fashion in a given regulatory gene network and only at particular time periods, thereby underpinning temporal local adaptation. These genes under positive selection provide subsequently the basis for spatial local adaptation to novel habitats when new ecological niches become available. Our results reveal the importance of jointly studying spatial and temporal adaptations in species during habitat colonization.

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