scholarly journals The impact of natural selection on the evolution and function of placentally expressed galectins

2018 ◽  
Author(s):  
Zackery A. Ely ◽  
Jiyun M. Moon ◽  
Gregory R. Sliwoski ◽  
Amandeep K. Sangha ◽  
Xing-Xing Shen ◽  
...  
Keyword(s):  
Natural Selection ◽  
Protein Structure ◽  
Genomic Variation ◽  
Human Populations ◽  
Carbohydrate Binding ◽  
Sequence Evolution ◽  
Placental Development ◽  
Human Genetic Disease ◽  
3D Protein Structure ◽  
The Impact

AbstractImmunity genes have repeatedly experienced natural selection during mammalian evolution. Galectins are carbohydrate-binding proteins that regulate diverse immune responses, including maternal-fetal immune tolerance in placental pregnancy. Seven human galectins, four conserved across vertebrates and three specific to primates, are involved in placental development. To comprehensively study the molecular evolution of these galectins both across mammals and within humans, we conducted a series of between-and within-species evolutionary analyses. By examining patterns of sequence evolution between species, we found that primate-specific galectins showed uniformly high substitution rates, whereas two of the four other galectins experienced accelerated evolution in primates. By examining human population genomic variation, we found that galectin genes and variants, including variants previously linked to immune diseases, showed signatures of recent positive selection in specific human populations. By examining one nonsynonymous variant in Galectin-8 previously associated with autoimmune diseases, we further discovered that it is tightly linked to three other nonsynonymous variants; surprisingly, the global frequency of this four-variant haplotype is ∼50%. To begin understanding the impact of this major haplotype on Galectin-8 protein structure, we modeled its 3D protein structure and found that it differed substantially from the reference protein structure. These results suggest that placentally expressed galectins experienced both ancient and more recent selection in a lineage-and population-specific manner. Furthermore, our discovery that the major Galectin-8 haplotype is structurally distinct from and more commonly found than the reference haplotype illustrates the significance of understanding the evolutionary processes that sculpted variants associated with human genetic disease.

scholarly journals The Impact of Natural Selection on the Evolution and Function of Placentally Expressed Galectins

2019 ◽  
Vol 11 (9) ◽  
pp. 2574-2592 ◽  
Author(s):  
Zackery A Ely ◽  
Jiyun M Moon ◽  
Gregory R Sliwoski ◽  
Amandeep K Sangha ◽  
Xing-Xing Shen ◽  
...  
Keyword(s):  
Natural Selection ◽  
Protein Structure ◽  
Genomic Variation ◽  
Human Populations ◽  
Carbohydrate Binding ◽  
Sequence Evolution ◽  
Placental Development ◽  
Human Genetic Disease ◽  
3D Protein Structure ◽  
The Impact

Abstract Immunity genes have repeatedly experienced natural selection during mammalian evolution. Galectins are carbohydrate-binding proteins that regulate diverse immune responses, including maternal–fetal immune tolerance in placental pregnancy. Seven human galectins, four conserved across vertebrates and three specific to primates, are involved in placental development. To comprehensively study the molecular evolution of these galectins, both across mammals and within humans, we conducted a series of between- and within-species evolutionary analyses. By examining patterns of sequence evolution between species, we found that primate-specific galectins showed uniformly high substitution rates, whereas two of the four other galectins experienced accelerated evolution in primates. By examining human population genomic variation, we found that galectin genes and variants, including variants previously linked to immune diseases, showed signatures of recent positive selection in specific human populations. By examining one nonsynonymous variant in Galectin-8 previously associated with autoimmune diseases, we further discovered that it is tightly linked to three other nonsynonymous variants; surprisingly, the global frequency of this four-variant haplotype is ∼50%. To begin understanding the impact of this major haplotype on Galectin-8 protein structure, we modeled its 3D protein structure and found that it differed substantially from the reference protein structure. These results suggest that placentally expressed galectins experienced both ancient and more recent selection in a lineage- and population-specific manner. Furthermore, our discovery that the major Galectin-8 haplotype is structurally distinct from and more commonly found than the reference haplotype illustrates the significance of understanding the evolutionary processes that sculpted variants associated with human genetic disease.

scholarly journals Protein Structure, Models of Sequence Evolution, and Data Type Effects in Phylogenetic Analyses of Mitochondrial Data: A Case Study in Birds

Diversity ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 555
Author(s):  
Emily L. Gordon ◽  
Rebecca T. Kimball ◽  
Edward L. Braun
Keyword(s):  
Amino Acids ◽  
Protein Structure ◽  
Amino Acid ◽  
Bird Species ◽  
Data Type ◽  
Substitution Matrix ◽  
Sequence Evolution ◽  
Transmembrane Helices ◽  
Encoded Proteins ◽  
The Impact

Phylogenomic analyses have revolutionized the study of biodiversity, but they have revealed that estimated tree topologies can depend, at least in part, on the subset of the genome that is analyzed. For example, estimates of trees for avian orders differ if protein-coding or non-coding data are analyzed. The bird tree is a good study system because the historical signal for relationships among orders is very weak, which should permit subtle non-historical signals to be identified, while monophyly of orders is strongly corroborated, allowing identification of strong non-historical signals. Hydrophobic amino acids in mitochondrially-encoded proteins, which are expected to be found in transmembrane helices, have been hypothesized to be associated with non-historical signals. We tested this hypothesis by comparing the evolution of transmembrane helices and extramembrane segments of mitochondrial proteins from 420 bird species, sampled from most avian orders. We estimated amino acid exchangeabilities for both structural environments and assessed the performance of phylogenetic analysis using each data type. We compared those relative exchangeabilities with values calculated using a substitution matrix for transmembrane helices estimated using a variety of nuclear- and mitochondrially-encoded proteins, allowing us to compare the bird-specific mitochondrial models with a general model of transmembrane protein evolution. To complement our amino acid analyses, we examined the impact of protein structure on patterns of nucleotide evolution. Models of transmembrane and extramembrane sequence evolution for amino acids and nucleotides exhibited striking differences, but there was no evidence for strong topological data type effects. However, incorporating protein structure into analyses of mitochondrially-encoded proteins improved model fit. Thus, we believe that considering protein structure will improve analyses of mitogenomic data, both in birds and in other taxa.

scholarly journals Protein Structure, Models of Sequence Evolution, and Data Type Effects in Phylogenetic Analyses of Mitochondrial Data: A Case Study in Birds

2021 ◽  
Author(s):  
Emily L. Gordon ◽  
Rebecca T. Kimball ◽  
Edward L. Braun
Keyword(s):  
Amino Acids ◽  
Protein Structure ◽  
Transmembrane Protein ◽  
Phylogenetic Analyses ◽  
Bird Species ◽  
Data Type ◽  
Sequence Evolution ◽  
Transmembrane Helices ◽  
Encoded Proteins ◽  
The Impact

Phylogenomic analyses have revolutionized the study of biodiversity, but they have revealed that estimated tree topologies can depend, at least in part, on the subset of the genome that is analyzed. For example, estimates of trees for avian orders differ if protein coding or non-coding data are analyzed. The bird tree is a good study system because the historical signal for relationships among orders is very weak, which should permit subtle non-historical signals to be identified, while monophyly of orders is strongly corroborated, allowing identification of strong non-historical signals. Hydrophobic amino acids in mitochondrially-encoded proteins, which are expected to be found in transmembrane helices, have been hypothesized to be associated with non-historical signals. We tested this hypothesis by comparing the evolution of transmembrane helices and extramembrane segments of mitochondrial proteins from 420 bird species, sampled from most avian orders. We estimated amino acids exchangeabilities for both structural environments and assessed the performance of phylogenetic analysis using each data type. We compared those relative exchangeabilities with values calculated using a substitution dataset for transmembrane helices from a variety of sampled set of nuclear- and mitochondrially-encoded proteins, allowing us to compare the bird-specific mitochondrial models with a general model of transmembrane protein evolution. To complement our amino acid analyses, we examined the impact of protein structure on patterns of nucleotide evolution. Models of transmembrane and extramembrane sequence evolution for amino acids and nucleotides exhibited striking differences, but there was no evidence for strong topological data type effects. However, incorporating protein structure into analyses of mitochondrially-encoded proteins improved model fit. Thus, we believe that considering protein structure will improve analyses of mitogenomic data, both in birds and in other taxa.

scholarly journals Food and fitness: associations between crop yields and life-history traits in a longitudinally monitored pre-industrial human population

2012 ◽  
Vol 279 (1745) ◽  
pp. 4165-4173 ◽  
Author(s):  
Adam D. Hayward ◽  
Jari Holopainen ◽  
Jenni E. Pettay ◽  
Virpi Lummaa
Keyword(s):  
Natural Selection ◽  
Crop Yields ◽  
Economic Status ◽  
Food Shortage ◽  
Human Populations ◽  
Fitness Traits ◽  
Animal Populations ◽  
Specific Mortality ◽  
Selection For ◽  
The Impact

Severe food shortage is associated with increased mortality and reduced reproductive success in contemporary and historical human populations. Studies of wild animal populations have shown that subtle variation in environmental conditions can influence patterns of mortality, fecundity and natural selection, but the fitness implications of such subtle variation on human populations are unclear. Here, we use longitudinal data on local grain production, births, marriages and mortality so as to assess the impact of crop yield variation on individual age-specific mortality and fecundity in two pre-industrial Finnish populations. Although crop yields and fitness traits showed profound year-to-year variation across the 70-year study period, associations between crop yields and mortality or fecundity were generally weak. However, post-reproductive individuals of both sexes, and individuals of lower socio-economic status experienced higher mortality when crop yields were low. This is the first longitudinal, individual-based study of the associations between environmental variation and fitness traits in pre-industrial humans, which emphasizes the importance of a portfolio of mechanisms for coping with low food availability in such populations. The results are consistent with evolutionary ecological predictions that natural selection for resilience to food shortage is likely to weaken with age and be most severe on those with the fewest resources.

scholarly journals The Impact of Recessive Deleterious Variation on Signals of Adaptive Introgression in Human Populations

Genetics ◽  
2020 ◽  
Vol 215 (3) ◽  
pp. 799-812 ◽  
Author(s):  
Xinjun Zhang ◽  
Bernard Kim ◽  
Kirk E. Lohmueller ◽  
Emilia Huerta-Sánchez
Keyword(s):  
Human Genome ◽  
False Positive ◽  
False Positive Rate ◽  
Genomic Variation ◽  
Human Populations ◽  
Deleterious Mutations ◽  
Recombination Rates ◽  
Adaptive Mutations ◽  
Adaptive Introgression ◽  
The Impact

Admixture with archaic hominins has altered the landscape of genomic variation in modern human populations. Several gene regions have been identified previously as candidates of adaptive introgression (AI) that facilitated human adaptation to specific environments. However, simulation-based studies have suggested that population genetic processes other than adaptive mutations, such as heterosis from recessive deleterious variants private to populations before admixture, can also lead to patterns in genomic data that resemble AI. The extent to which the presence of deleterious variants affect the false-positive rate and the power of current methods to detect AI has not been fully assessed. Here, we used extensive simulations under parameters relevant for human evolution to show that recessive deleterious mutations can increase the false positive rates of tests for AI compared to models without deleterious variants, especially when the recombination rates are low. We next examined candidates of AI in modern humans identified from previous studies, and show that 24 out of 26 candidate regions remain significant, even when deleterious variants are included in the null model. However, two AI candidate genes, HYAL2 and HLA, are particularly susceptible to high false positive signals of AI due to recessive deleterious mutations. These genes are located in regions of the human genome with high exon density together with low recombination rate, factors that we show increase the rate of false-positives due to recessive deleterious mutations. Although the combination of such parameters is rare in the human genome, caution is warranted in such regions, as well as in other species with more compact genomes and/or lower recombination rates. In sum, our results suggest that recessive deleterious mutations cannot account for the signals of AI in most, but not all, of the top candidates for AI in humans, suggesting they may be genuine signals of adaptation.

scholarly journals Differences in local population history at the finest level: the case of the Estonian population

2020 ◽  
Vol 28 (11) ◽  
pp. 1580-1591 ◽  
Author(s):  
Vasili Pankratov ◽  
Francesco Montinaro ◽  
Alena Kushniarevich ◽  
Georgi Hudjashov ◽  
Flora Jay ◽  
...  
Keyword(s):  
Natural Selection ◽  
Genetic Structure ◽  
Population Size ◽  
Effective Population Size ◽  
Local Population ◽  
Population History ◽  
Human Populations ◽  
Effective Population ◽  
The Impact ◽  
Estonian Population

Abstract Several recent studies detected fine-scale genetic structure in human populations. Hence, groups conventionally treated as single populations harbour significant variation in terms of allele frequencies and patterns of haplotype sharing. It has been shown that these findings should be considered when performing studies of genetic associations and natural selection, especially when dealing with polygenic phenotypes. However, there is little understanding of the practical effects of such genetic structure on demography reconstructions and selection scans when focusing on recent population history. Here we tested the impact of population structure on such inferences using high-coverage (~30×) genome sequences of 2305 Estonians. We show that different regions of Estonia differ in both effective population size dynamics and signatures of natural selection. By analyzing identity-by-descent segments we also reveal that some Estonian regions exhibit evidence of a bottleneck 10–15 generations ago reflecting sequential episodes of wars, plague and famine, although this signal is virtually undetected when treating Estonia as a single population. Besides that, we provide a framework for relating effective population size estimated from genetic data to actual census size and validate it on the Estonian population. This approach may be widely used both to cross-check estimates based on historical sources as well as to get insight into times and/or regions with no other information available. Our results suggest that the history of human populations within the last few millennia can be highly region specific and cannot be properly studied without taking local genetic structure into account.

Systematic benchmark of ancient DNA read mapping

2021 ◽  
Author(s):  
Adrien Oliva ◽  
Raymond Tobler ◽  
Alan Cooper ◽  
Bastien Llamas ◽  
Yassine Souilmi
Keyword(s):  
Ancient Dna ◽  
Dna Sequences ◽  
Population Genetic ◽  
Reference Genome ◽  
Population Data ◽  
Human Populations ◽  
Current Standard ◽  
Read Mapping ◽  
Reference Bias ◽  
The Impact

Abstract The current standard practice for assembling individual genomes involves mapping millions of short DNA sequences (also known as DNA ‘reads’) against a pre-constructed reference genome. Mapping vast amounts of short reads in a timely manner is a computationally challenging task that inevitably produces artefacts, including biases against alleles not found in the reference genome. This reference bias and other mapping artefacts are expected to be exacerbated in ancient DNA (aDNA) studies, which rely on the analysis of low quantities of damaged and very short DNA fragments (~30–80 bp). Nevertheless, the current gold-standard mapping strategies for aDNA studies have effectively remained unchanged for nearly a decade, during which time new software has emerged. In this study, we used simulated aDNA reads from three different human populations to benchmark the performance of 30 distinct mapping strategies implemented across four different read mapping software—BWA-aln, BWA-mem, NovoAlign and Bowtie2—and quantified the impact of reference bias in downstream population genetic analyses. We show that specific NovoAlign, BWA-aln and BWA-mem parameterizations achieve high mapping precision with low levels of reference bias, particularly after filtering out reads with low mapping qualities. However, unbiased NovoAlign results required the use of an IUPAC reference genome. While relevant only to aDNA projects where reference population data are available, the benefit of using an IUPAC reference demonstrates the value of incorporating population genetic information into the aDNA mapping process, echoing recent results based on graph genome representations.

Interactions Between Natural Selection, Recombination and Gene Density in the Genes of Drosophila

Genetics ◽  
2002 ◽  
Vol 160 (2) ◽  
pp. 595-608 ◽  
Author(s):  
Jody Hey ◽  
Richard M Kliman
Keyword(s):  
Gene Expression ◽  
Natural Selection ◽  
Recombination Rate ◽  
Codon Bias ◽  
Gene Density ◽  
Drosophila Genome ◽  
Functional Variation ◽  
Subtle Effect ◽  
Efficiency Of Selection ◽  
The Impact

AbstractIn Drosophila, as in many organisms, natural selection leads to high levels of codon bias in genes that are highly expressed. Thus codon bias is an indicator of the intensity of one kind of selection that is experienced by genes and can be used to assess the impact of other genomic factors on natural selection. Among 13,000 genes in the Drosophila genome, codon bias has a slight positive, and strongly significant, association with recombination—as expected if recombination allows natural selection to act more efficiently when multiple linked sites segregate functional variation. The same reasoning leads to the expectation that the efficiency of selection, and thus average codon bias, should decline with gene density. However, this prediction is not confirmed. Levels of codon bias and gene expression are highest for those genes in an intermediate range of gene density, a pattern that may be the result of a tradeoff between the advantages for gene expression of close gene spacing and disadvantages arising from regulatory conflicts among tightly packed genes. These factors appear to overlay the more subtle effect of linkage among selected sites that gives rise to the association between recombination rate and codon bias.

scholarly journals A comparative study on the extraction effects of common agents on collagen-based binders in mural paintings

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jianghao Du ◽  
Zhanyun Zhu ◽  
Junchang Yang ◽  
Jia Wang ◽  
Xiaotong Jiang
Keyword(s):  
Protein Structure ◽  
Comparative Study ◽  
Protein Extraction ◽  
Guanidine Hydrochloride ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Extraction Process ◽  
Ultraviolet Absorption Spectrum ◽  
Mural Paintings ◽  
The Impact

AbstractIn this paper, a comparative study was conducted on the extraction effects of six agents for collagen-based mural painting binders. These agents were used to extract the residual proteins in the non-aged and thermal aged samples. The protein extraction efficiencies of different extracting agents were quantitatively determined by bicinchoninic acid (BCA) method, and then processed by multivariate analysis of variance (MANOVA). The impact of the extraction process on the protein structure was characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), ultraviolet absorption spectrum (UV) and circular dichroism (CD). The results showed that, for both non-aged and aged samples, the extraction efficiency of 2 M guanidine hydrochloride (GuHCl) was significantly higher than the other five agents, with less damage to the protein structure during the extraction process.

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