scholarly journals Revisiting the evolutionary analysis of mammalian CRISPs reveals positive selection

2018 ◽  
Author(s):  
Alberto Vicens ◽  
Claudia Treviño
Keyword(s):  
Positive Selection ◽  
Adaptive Evolution ◽  
Negative Selection ◽  
Secretory Proteins ◽  
Evolutionary Analysis ◽  
Episodic Selection ◽  
Show Evidence ◽  
Selection For ◽  
Related Proteins

AbstractCysteine-rich secretory proteins (CRISPs) constitute a versatile family, with functions that include being components of reptilian venom and participation in mammalian reproduction. While non-mammalian vertebrates express a single CRISP gene, mammals generally express three CRISP paralogs. A previous study assessing the molecular evolution of vertebrate CRISPs revealed strong positive selection in reptilian CRISP and negative selection in mammalian CRISPs. In this study, we re-assessed molecular adaptation of mammalian CRISPs through an analysis of larger sequence datasets that represent mammalian diversity. Our analyses show evidence of recent episodes of positive selection for all mammalian CRISPs. Intensity of positive selection was heterogeneous both among CRISP paralogs (being stronger in CRISP3 than in CRISP1 and CRISP2) and across functional domains (having more impact on CRD or PR-1 domain). Analysis of episodic selection did not yield strong signatures of adaptive evolution in any particular mammalian group, suggesting that positive selection was more pervasive on mammalian CRISPs. Our findings provide evidence of adaptive evolution in a family of reproduction-related proteins, and offer interesting insights regarding the role of mammalian CRISPs in fertility and speciation.

scholarly journals Host-Virus Arms Races Drive Elevated Adaptive Evolution in Viral Receptors

2020 ◽  
Vol 94 (16) ◽  
Author(s):  
Wenqiang Wang ◽  
Huayao Zhao ◽  
Guan-Zhu Han
Keyword(s):  
Positive Selection ◽  
Local Adaptation ◽  
Adaptive Evolution ◽  
Negative Selection ◽  
Host Cells ◽  
Human Populations ◽  
Arms Races ◽  
Selection Pressures ◽  
Selection For ◽  
Viral Receptors

ABSTRACT Viral receptors are the cell surface proteins that are hijacked by viruses to initialize their infections. Viral receptors are subject to two conflicting directional forces, namely, negative selection due to functional constraints and positive selection due to host-virus arms races. It remains largely obscure whether negative pleiotropy limits the rate of adaptation in viral receptors. Here, we perform evolutionary analyses of 96 viral receptor genes in primates and find that 41 out of 96 viral receptors experienced adaptive evolution. Many positively selected residues in viral receptors are located at the virus-receptor interfaces. Compared with control proteins, viral receptors exhibit significantly elevated rate of adaptation. Further analyses of genetic polymorphisms in human populations reveal signals of positive selection and balancing selection for 53 and 5 viral receptors, respectively. Moreover, we find that 49 viral receptors experienced different selection pressures in different human populations, indicating that viruses represent an important driver of local adaptation in humans. Our findings suggest that diverse viruses, many of which have not been known to infect nonhuman primates, have maintained antagonistic associations with primates for millions of years, and the host-virus conflicts drive accelerated adaptive evolution in viral receptors. IMPORTANCE Viruses hijack cellular proteins, termed viral receptors, to assist their entry into host cells. While viral receptors experience negative selection to maintain their normal functions, they also undergo positive selection due to an everlasting evolutionary arms race between viruses and hosts. A complete picture on how viral receptors evolve under two conflicting forces is still lacking. In this study, we systematically analyzed the evolution of 96 viral receptors in primates and human populations. We found around half of viral receptors underwent adaptive evolution and exhibit significantly elevated rates of adaptation compared to control genes in primates. We also found signals of past natural selection for 58 viral receptors in human populations. Interestingly, 49 viral receptors experienced different selection pressures in different human populations, indicating that viruses represent an important driver of local adaptation in humans. Our results suggest that host-virus arms races drive accelerated adaptive evolution in viral receptors.

scholarly journals Paradoxical Signaling Pathways in Developing Thymocytes

2011 ◽  
Vol 14 (3) ◽  
pp. 378 ◽  
Author(s):  
Aws Alshamsan
Keyword(s):  
Cell Death ◽  
Positive Selection ◽  
Cell Fate ◽  
Negative Selection ◽  
Mapk Pathway ◽  
Erk Activation ◽  
Selection For ◽  
Kinetics Of ◽  
Level Order

ABSTRACT- Thymocytes are subjected to processes of selection during their life in the thymus; negative selection for autoreactive thymocytes and positive selection for self-MHC restricted self-tolerant cells. Interestingly, signals for positive or negative selection originate from the same receptor. More importantly, evidence showed that both death and survival signals are mediated by the MAPK pathway. The degree and order of ERK activation, but not other MAPK proteins, has been found to be different in either cases of cell fate. Therefore, it is suspected that the kinetics of ERK after activation may dictate cell death or survival. There are two important GEF proteins that are involved in Ras/ERK activation, RasGRP and SOS. It is thought that the level, order and kinetics of ERK are influenced upstream by the type of GEF. This review discusses the role of both GEF proteins in positive and negative selection and how this reflects on ERK activation. This article is open POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Integrated structural and evolutionary analysis reveals common mechanisms underlying adaptive evolution in mammals

2020 ◽  
Vol 117 (11) ◽  
pp. 5977-5986 ◽  
Author(s):  
Greg Slodkowicz ◽  
Nick Goldman
Keyword(s):  
Positive Selection ◽  
Adaptive Evolution ◽  
Evolutionary Biology ◽  
Molecular Mechanisms ◽  
Structural Information ◽  
Protein Structures ◽  
Unexpected Finding ◽  
Evolutionary Analysis ◽  
Genomic Scale ◽  
Evolution Of Mammals

Understanding the molecular basis of adaptation to the environment is a central question in evolutionary biology, yet linking detected signatures of positive selection to molecular mechanisms remains challenging. Here we demonstrate that combining sequence-based phylogenetic methods with structural information assists in making such mechanistic interpretations on a genomic scale. Our integrative analysis shows that positively selected sites tend to colocalize on protein structures and that positively selected clusters are found in functionally important regions of proteins, indicating that positive selection can contravene the well-known principle of evolutionary conservation of functionally important regions. This unexpected finding, along with our discovery that positive selection acts on structural clusters, opens previously unexplored strategies for the development of better models of protein evolution. Remarkably, proteins where we detect the strongest evidence of clustering belong to just two functional groups: Components of immune response and metabolic enzymes. This gives a coherent picture of pathogens and xenobiotics as important drivers of adaptive evolution of mammals.

scholarly journals New insights on equid locomotor evolution from the lumbar region of fossil horses

2016 ◽  
Vol 283 (1829) ◽  
pp. 20152947 ◽  
Author(s):  
Katrina Elizabeth Jones
Keyword(s):  
Body Size ◽  
Adaptive Evolution ◽  
Axial Skeleton ◽  
Lumbar Region ◽  
Scaling Effects ◽  
Classic Case ◽  
Strong Selection ◽  
Selection For ◽  
Joint Shape

The specialization of equid limbs for cursoriality is a classic case of adaptive evolution, but the role of the axial skeleton in this famous transition is not well understood. Extant horses are extremely fast and efficient runners, which use a stiff-backed gallop with reduced bending of the lumbar region relative to other mammals. This study tests the hypothesis that stiff-backed running in horses evolved in response to evolutionary increases in body size by examining lumbar joint shape from a broad sample of fossil equids in a phylogenetic context. Lumbar joint shape scaling suggests that stability of the lumbar region does correlate with size through equid evolution. However, scaling effects were dampened in the posterior lumbar region, near the sacrum, which suggests strong selection for sagittal mobility in association with locomotor–respiratory coupling near the lumbosacral joint. I hypothesize that small-bodied fossil horses may have used a speed-dependent running gait, switching between stiff-backed and flex-backed galloping as speed increased.

scholarly journals Preliminary assessment of adaptive evolution of mitochondrial protein coding genes in darters (Percidae: Etheostomatinae)

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 464 ◽  
Author(s):  
Leos G. Kral ◽  
Sara Watson
Keyword(s):  
Positive Selection ◽  
Adaptive Evolution ◽  
Gene Evolution ◽  
Mitochondrial Gene ◽  
Mitochondrial Protein ◽  
Preliminary Assessment ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Show Evidence ◽  
Selection Of

Background: Mitochondrial DNA of vertebrates contains genes for 13 proteins involved in oxidative phosphorylation. Some of these genes have been shown to undergo adaptive evolution in a variety of species. This study examines all mitochondrial protein coding genes in 11 darter species to determine if any of these genes show evidence of positive selection. Methods: The mitogenome from four darter was sequenced and annotated. Mitogenome sequences for another seven species were obtained from GenBank. Alignments of each of the protein coding genes were subject to codon-based identification of positive selection by Selecton, MEME and FEL. Results: Evidence of positive selection was obtained for six of the genes by at least one of the methods. CYTB was identified as having evolved under positive selection by all three methods at the same codon location. Conclusions: Given the evidence for positive selection of mitochondrial protein coding genes in darters, a more extensive analysis of mitochondrial gene evolution in all the extant darter species is warranted.

scholarly journals Use of signals of positive and negative selection to distinguish cancer genes and passenger genes

2020 ◽  
Author(s):  
László Bányai ◽  
Mária Trexler ◽  
Krisztina Kerekes ◽  
Orsolya Csuka ◽  
László Patthy
Keyword(s):  
Negative Selection ◽  
Cancer Genomics ◽  
Tumor Evolution ◽  
Cancer Genes ◽  
Cancer Evolution ◽  
Human Genes ◽  
Strong Negative Selection ◽  
Selection For ◽  
Inactivating Mutations

AbstractA major goal of cancer genomics is to identify all genes that play critical roles in carcinogenesis. Most approaches focused on genes that are positively selected for mutations that drive carcinogenesis and neglected the role of negative selection. Some studies have actually concluded that negative selection has no role in cancer evolution. In the present work we have re-examined the role of negative selection in tumor evolution through the analysis of the patterns of somatic mutations affecting the coding sequences of human genes. Our analyses have confirmed that tumor suppressor genes are positively selected for inactivating mutations. Oncogenes, however, were found to display signals of both negative selection for inactivating mutations and positive selection for activating mutations. Significantly, we have identified numerous human genes that show signs of strong negative selection during tumor evolution, suggesting that their functional integrity is essential for the growth and survival of tumor cells.

scholarly journals Adaptive evolution in DNMT2 supports its role in the dipteran immune response

2020 ◽  
Author(s):  
Tamanash Bhattacharya ◽  
Danny W. Rice ◽  
Richard W. Hardy ◽  
Irene L.G. Newton
Keyword(s):  
Immune Response ◽  
Positive Selection ◽  
Adaptive Evolution ◽  
Fruit Fly ◽  
Fruit Flies ◽  
Host Protein ◽  
Specific Host ◽  
Wide Range ◽  
Specific Factors

AbstractEukaryotic nucleic acid methyltransferase (MTase) proteins are essential mediators of epigenetic and epitranscriptomic regulation. DNMT2 belongs to a large, conserved family of DNA MTases found in many organisms, including holometabolous insects like fruit flies and mosquitoes, where it is the lone MTase. Interestingly, despite its nomenclature, DNMT2 is not a DNA MTase, but instead targets and methylates RNA species. A growing body of literature suggest DNMT2 mediates the host immune response against a wide range of pathogens, including RNA viruses. Evidence of adaptive evolution, in the form of positive selection, can often be found in genes that are engaged in conflict with pathogens like viruses. Here we identify and describe evidence of positive selection that has occurred at different times over the course of DNMT2 evolution within dipteran insects. We identify specific codons within each ortholog that are under positive selection, and find they are restricted to four distinct domains of the protein and likely influence substrate binding, target recognition, and adaptation of unique intermolecular interactions. Additionally, we describe the role of the Drosophila-specific host protein IPOD, in regulating the expression and/or function of fruit fly DNMT2. Finally, heterologous expression of these orthologs suggest that DNMT2’s role as an antiviral is host dependent, indicating a requirement for additional host-specific factors. Collectively, our findings highlight the adaptive evolution of DNMT2 in Dipteran insects, underscoring its role as an important, albeit non-canonical, regulator of host-pathogen interactions in mosquitoes and fruit flies.

scholarly journals Epigenomic co-localization and co-evolution reveal a key role for 5hmC as a communication hub in the chromatin network of ESCs

2014 ◽  
Author(s):  
David Juan ◽  
Juliane Perner ◽  
Enrique Carrillo de Santa Pau ◽  
Simone Marsili ◽  
David Ochoa ◽  
...  
Keyword(s):  
Communication Network ◽  
Dna Demethylation ◽  
Communication Model ◽  
Evolutionary Analysis ◽  
Manual Annotation ◽  
Nucleosome Remodeling ◽  
Location Data ◽  
Genome Wide ◽  
Related Proteins

Epigenetic communication through histone and cytosine modifications is essential for gene regulation and cell identity. Here, we propose a framework that is based on a chromatin communication model to get insight on the function of epigenetic modifications in ESCs. The epigenetic communication network was inferred from genome-wide location data plus extensive manual annotation. Notably, we found that 5-hydroxymethylcytosine (5hmC) is the most influential hub of this network, connecting DNA demethylation to nucleosome remodeling complexes and to key transcription factors of pluripotency. Moreover, an evolutionary analysis revealed a central role of 5hmC in the co-evolution of chromatin-related proteins. Further analysis of regions where 5hmC colocalizes with specific interactors shows that each interaction points to chromatin remodelling, stemness, differentiation or metabolism. Our results highlight the importance of cytosine modifications in the epigenetic communication of ESCs.

scholarly journals Thymus-derived Glucocorticoids Regulate Antigen-specific Positive Selection

1997 ◽  
Vol 185 (11) ◽  
pp. 2033-2038 ◽  
Author(s):  
Melanie S. Vacchio ◽  
Jonathan D. Ashwell
Keyword(s):  
Positive Selection ◽  
Negative Selection ◽  
Cross Linking ◽  
Thymocyte Development ◽  
Organ Cultures ◽  
Specific Loss ◽  
Histocompatibility Complex ◽  
Glucocorticoid Production ◽  
Self Antigen

While it is generally believed that the avidity of the T cell antigen receptor (TCR) for self antigen/major histocompatibility complex (MHC) determines a thymocyte's fate, how the cell discriminates between a stimulus that causes positive selection (survival) and one that causes negative selection (death) is unknown. We have previously demonstrated that glucocorticoids are produced in the thymus, and that they antagonize deletion caused by TCR cross-linking. To examine the role of glucocorticoids during MHC-dependent selection, we examined thymocyte development in organ cultures in which corticosteroid biosynthesis was inhibited. Inhibition of glucocorticoid production in thymi from α/β-TCR transgenic mice resulted in the antigen- and MHC-specific loss of thymocytes that normally recognize self antigen/MHC with sufficient avidity to result in positive selection. Furthermore, inhibition of glucocorticoid production caused an increase in apoptosis only in CD+CD8+ thymocytes bearing transgenic TCRs that recognized self antigen/MHC. These results indicate that the balance of TCR and glucocorticoid receptor signaling influences the antigen-specific thymocyte development by allowing cells with low-to-moderate avidity for self antigen/MHC to survive.

scholarly journals Variant analysis of the sporozoite surface antigen gene reveals that asymptomatic cattle from wildlife-livestock interface areas in northern Tanzania harbour buffalo-derived T. parva

2020 ◽  
Vol 119 (11) ◽  
pp. 3817-3828
Author(s):  
Micky M. Mwamuye ◽  
David Odongo ◽  
Yvette Kazungu ◽  
Fatuma Kindoro ◽  
Paul Gwakisa ◽  
...  
Keyword(s):  
Positive Selection ◽  
Target Antigen ◽  
Evolutionary Analysis ◽  
East African ◽  
Parasite Genotype ◽  
Northern Tanzania ◽  
Cell Target ◽  
Show Evidence ◽  
Variant Analysis ◽  
Central Kenya

Abstract Buffalo-derived Theileria parva can ‘break through’ the immunity induced by the infection and treatment vaccination method (ITM) in cattle. However, no such ‘breakthroughs’ have been reported in northern Tanzania where there has been long and widespread ITM use in pastoralist cattle, and the Cape buffalo (Syncerus caffer) is also present. We studied the exposure of vaccinated and unvaccinated cattle in northern Tanzania to buffalo-derived T. parva using p67 gene polymorphisms and compared this to its distribution in vaccinated cattle exposed to buffalo-derived T. parva in central Kenya, where vaccine ‘breakthroughs’ have been reported. Additionally, we analysed the CD8+ T cell target antigen Tp2 for positive selection. Our results showed that 10% of the p67 sequences from Tanzanian cattle (n = 39) had a buffalo type p67 (allele 4), an allele that is rare among East African isolates studied so far. The percentage of buffalo-derived p67 alleles observed in Kenyan cattle comprised 19% of the parasites (n = 36), with two different p67 alleles (2 and 3) of presumptive buffalo origin. The Tp2 protein was generally conserved with only three Tp2 variants from Tanzania (n = 33) and five from Kenya (n = 40). Two Tanzanian Tp2 variants and two Kenyan Tp2 variants were identical to variants present in the trivalent Muguga vaccine. Tp2 evolutionary analysis did not show evidence for positive selection within previously mapped epitope coding sites. The p67 data indicates that some ITM-vaccinated cattle are protected against disease induced by a buffalo-derived T. parva challenge in northern Tanzania and suggests that the parasite genotype may represent one factor explaining this.

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