scholarly journals Suboptimal intermediates underlie evolution of the Bicoid homeodomain

2020 ◽  
Author(s):  
Pinar Onal ◽  
Himari Imaya Gunasinghe ◽  
Kristaley Yui Umezawa ◽  
Michael Zheng ◽  
Jia Ling ◽  
...  
Keyword(s):  
Amino Acid ◽  
Regulatory Networks ◽  
Phenotypic Diversity ◽  
Regulatory Elements ◽  
Amino Acid Sequences ◽  
The Body ◽  
Embryo Patterning ◽  
Dna And Rna ◽  
Evolutionary Changes ◽  
Transcription Networks

AbstractChanges in regulatory networks generate materials for evolution to create phenotypic diversity. For transcription networks, multiple studies have shown that alterations in binding sites of cis-regulatory elements correlate well with the gain or loss of specific features of the body plan. Less is known about alterations in the amino acid sequences of the transcription factors (TFs) that bind these elements. Here we study the evolution of Bicoid (Bcd), a homeodomain (HD) protein that is critical for anterior embryo patterning in Drosophila. The ancestor of Bcd (AncBcd) emerged after a duplication of a Zerknullt (Zen)-like ancestral protein (AncZB) in a suborder of flies. AncBcd diverged from AncZB, gaining novel transcriptional and translational activities. We focus on the evolution of the HD of AncBcd, which binds DNA and RNA, and is comprised of four subdomains: an N-terminal arm (NT) and three helices; H1, H2, and Recognition Helix (RH). Using chimeras of subdomains and gene rescue assays in Drosophila, we show that robust patterning activity of the Bcd HD (high frequency rescue to adulthood) is achieved only when amino acid substitutions in three separate subdomains (NT, H1, and RH) are combined. Other combinations of subdomains also yield full rescue, but with lower penetrance, suggesting alternative suboptimal activities. Our results suggest a multi-step pathway for the evolution of the Bcd HD that involved intermediate HD sequences with suboptimal activities, which constrained and enabled further evolutionary changes. They also demonstrate critical epistatic forces that contribute to the robust function of a DNA-binding domain.

scholarly journals Suboptimal Intermediates Underlie Evolution of the Bicoid Homeodomain

2021 ◽  
Author(s):  
Pinar Onal ◽  
Himari Imaya Gunasinghe ◽  
Kristaley Yui Umezawa ◽  
Michael Zheng ◽  
Jia Ling ◽  
...  
Keyword(s):  
Amino Acid ◽  
Regulatory Networks ◽  
Phenotypic Diversity ◽  
Regulatory Elements ◽  
Amino Acid Sequences ◽  
The Body ◽  
Embryo Patterning ◽  
Dna And Rna ◽  
Evolutionary Changes ◽  
Transcription Networks

Abstract Changes in regulatory networks generate materials for evolution to create phenotypic diversity. For transcription networks, multiple studies have shown that alterations in binding sites of cis-regulatory elements correlate well with the gain or loss of specific features of the body plan. Less is known about alterations in the amino acid sequences of the transcription factors (TFs) that bind these elements. Here we study the evolution of Bicoid (Bcd), a homeodomain (HD) protein that is critical for anterior embryo patterning in Drosophila. The ancestor of Bcd (AncBcd) emerged after a duplication of a Zerknullt (Zen)-like ancestral protein (AncZB) in a suborder of flies. AncBcd diverged from AncZB, gaining novel transcriptional and translational activities. We focus on the evolution of the HD of AncBcd, which binds to DNA and RNA, and is comprised of four subdomains: an N-terminal arm (NT) and three helices; H1, H2, and Recognition Helix (RH). Using chimeras of subdomains and gene rescue assays in Drosophila, we show that robust patterning activity of the Bcd HD (high frequency rescue to adulthood) is achieved only when amino acid substitutions in three separate subdomains (NT, H1, and RH) are combined. Other combinations of subdomains also yield full rescue, but with lower penetrance, suggesting alternative suboptimal activities. Our results suggest a multi-step pathway for the evolution of the Bcd HD that involved intermediate HD sequences with suboptimal activities, which constrained and enabled further evolutionary changes. They also demonstrate critical epistatic forces that contribute to the robust function of a DNA-binding domain.

scholarly journals Evolution and Adaptation of the Avian H7N9 Virus into the Human Host

2020 ◽  
Vol 8 (5) ◽  
pp. 778
Author(s):  
Andrew T. Bisset ◽  
Gerard F. Hoyne
Keyword(s):  
Amino Acid ◽  
Avian Influenza ◽  
Influenza A ◽  
Amino Acid Sequences ◽  
Influenza Viruses ◽  
Amino Acid Substitutions ◽  
Upper Respiratory Tract ◽  
Viral Polymerase ◽  
Evolutionary Changes ◽  
Avian Origin

Influenza viruses arise from animal reservoirs, and have the potential to cause pandemics. In 2013, low pathogenic novel avian influenza A(H7N9) viruses emerged in China, resulting from the reassortment of avian-origin viruses. Following evolutionary changes, highly pathogenic strains of avian influenza A(H7N9) viruses emerged in late 2016. Changes in pathogenicity and virulence of H7N9 viruses have been linked to potential mutations in the viral glycoproteins hemagglutinin (HA) and neuraminidase (NA), as well as the viral polymerase basic protein 2 (PB2). Recognizing that effective viral transmission of the influenza A virus (IAV) between humans requires efficient attachment to the upper respiratory tract and replication through the viral polymerase complex, experimental evidence demonstrates the potential H7N9 has for increased binding affinity and replication, following specific amino acid substitutions in HA and PB2. Additionally, the deletion of extended amino acid sequences in the NA stalk length was shown to produce a significant increase in pathogenicity in mice. Research shows that significant changes in transmissibility, pathogenicity and virulence are possible after one or a few amino acid substitutions. This review aims to summarise key findings from that research. To date, all strains of H7N9 viruses remain restricted to avian reservoirs, with no evidence of sustained human-to-human transmission, although mutations in specific viral proteins reveal the efficacy with which these viruses could evolve into a highly virulent and infectious, human-to-human transmitted virus.

scholarly journals Evolutionary Analysis of Transcriptional Regulation Mediated by Cdx2 in Rodents

2021 ◽  
Author(s):  
Weizheng Liang ◽  
Guipeng Li ◽  
Huanhuan Cui ◽  
Yukai Wang ◽  
Wencheng Wei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Amino Acid ◽  
Dna Binding ◽  
Phenotypic Diversity ◽  
Embryonic Stem ◽  
Regulatory Elements ◽  
Evolutionary Analysis ◽  
Protein Sequence Analysis ◽  
Systematic Analysis

AbstractDifferences in gene expression, which can arise from divergence in cis-regulatory elements or alterations in transcription factors binding specificity, are one of the most important causes of phenotypic diversity during evolution. By protein sequence analysis, we observed high sequence conservation in the DNA binding domain (DBD) of the transcription factor Cdx2 across many vertebrates, whereas three amino acid changes were exclusively found in mouse Cdx2 (mCdx2), suggesting potential positive selection in the mouse lineage. Multi-omics analyses were then carried out to investigate the effects of these changes. Surprisingly, there were no significant functional differences between mCdx2 and its rat homologue (rCdx2), and none of the three amino acid changes had any impact on its function. Finally, we used rat-mouse allodiploid embryonic stem cells (RMES) to study the cis effects of Cdx2-mediated gene regulation between the two rodents. Interestingly, whereas Cdx2 binding is largely divergent between mouse and rat, the transcriptional effect induced by Cdx2 is conserved to a much larger extent.Author summaryOur study 1) represented a first systematic analysis of species-specific adaptation in DNA binding pattern of transcription factor. Although the mouse-specific amino acid changes did not manifest functional impact in our system, several explanations may account for it (See Discussion part for the detail); 2) represented a first study of cis-regulation between two reproductively isolated species by using a novel allodiploid system; 3) demonstrated a higher conservation of transcriptional output than that of DNA binding, suggesting the evolvability/plasticity of the latter; 4) finally provided a rich data resource for Cdx2 mediated regulation, including gene expression, chromatin accessibility and DNA binding etc.

scholarly journals Paradigms and paradoxes: decoding the “genetic code”

2020 ◽  
Vol 32 (1) ◽  
pp. 9-10
Author(s):  
Stephen John Knabel ◽  
Istvan Hargittai
Keyword(s):  
Amino Acid ◽  
Nucleotide Sequence ◽  
Genetic Code ◽  
Amino Acid Sequences ◽  
Dna And Rna ◽  
Genetic Codes

AbstractWe propose to keep the term “genetic code” to describe the nucleotide sequence in DNA and RNA and use the term “genetic cipher” to describe the key for decoding the genetic codes of DNA and RNA into the amino acid sequences of proteins.

scholarly journals Sequence analysis and structure prediction of ABHD16A and the roles of the ABHD family members in human disease

Open Biology ◽  
2018 ◽  
Vol 8 (5) ◽  
pp. 180017 ◽  
Author(s):  
Jun Xu ◽  
Weizhen Gu ◽  
Kai Ji ◽  
Zhao Xu ◽  
Haihua Zhu ◽  
...  
Keyword(s):  
Amino Acid ◽  
Structure Prediction ◽  
Active Sites ◽  
Metabolic Regulation ◽  
Acid Sites ◽  
Amino Acid Sequences ◽  
The Body ◽  
Gene Location ◽  
Future Research ◽  
Animal Cells

Abhydrolase domain containing 16A (ABHD16A) is a member of the α/β hydrolase domain-containing (ABHD) protein family and is expressed in a variety of animal cells. Studies have shown that ABHD16A has acylglycerol lipase and phosphatidylserine lipase activities. Its gene location in the main histocompatibility complex (MHC) III gene cluster suggests that this protein may participate in the immunomodulation of the body. The results of studies investigating nearly 20 species of ABHDs reveal that the ABHD proteins are key factors in metabolic regulation and disease occurrence and development. In this paper, we summarize the related progress regarding the function of ABHD16A and other ABHD proteins. A prediction of the active sites and structural domains of ABHD16A and an analysis of the amino acid sites are included. Moreover, we analysed the amino acid sequences of the ABHD16A molecules in different species and provide an overview of the related functions and diseases associated with these proteins. The functions and diseases related to ABHD are systematically summarized and highlighted. Future research directions for studies investigating the functions and mechanisms of these proteins are also suggested. Further studies investigating the function of ABHD proteins may further confirm their positions as important determinants of lipid metabolism and related diseases.

scholarly journals Acrylamide: a Hidden Danger

2019 ◽  
Vol 1 (1) ◽  
pp. 113-117
Author(s):  
Burhan Başaran ◽  
Ferid Aydin
Keyword(s):  
Heat Treatment ◽  
Nervous System ◽  
Amino Acid ◽  
High Temperatures ◽  
Maillard Reaction ◽  
Reducing Sugar ◽  
The Body ◽  
International Agency ◽  
Carcinogenic Substance ◽  
Dna And Rna

Acrylamide, which is known to exist in a range of foodstuffs at different rates is a heat treatment contaminant and has been labeled by the International Agency for Research on Cancer as a probable carcinogenic substance for humans. Acrylamide is readily absorbed by the body and it spreads to the tissues. The fact that acrylamide is highly prone to react with DNA and RNA has brought forward various health problems as well. Many studies have proved the relation between acrylamide and diseases related to the nervous system, notably cancer. The most important mechanism in the formation of acrylamide in foodstuffs is the Maillard reaction. The level of acrylamide in foodstuffs shows an increase in high temperatures especially in the presence of reducing sugar and asparagine amino acid. However, no legal legislation has yet been defined on the level of acrylamide in foodstuffs.

The evolution of plants and animals under domestication: the contribution of studies at the molecular level

1976 ◽  
Vol 275 (936) ◽  
pp. 99-116 ◽  
Keyword(s):  
Amino Acid ◽  
Biological Function ◽  
Quaternary Structure ◽  
Sequence Data ◽  
Three Dimensional ◽  
Amino Acid Sequences ◽  
Molecular Structures ◽  
Coding System ◽  
Dna And Rna ◽  
Protein Molecules

Protein molecules are essential catalysts in life processes and also form much of the substance of living material. Their three dimensional structures determine their biological function. Their biosynthesis is primarily determined by arrays of nucleic acid macromolecules (DNA and RNA), and the amino acid sequences that constitute their long spatially organized peptide-chain molecules reflect at one remove this DNA coding system, and thus record a step-by-step history of some of the viable genetic events (natural or man-controlled) that have created the organism and the breed. Amino acid sequences can be used to trace the progress of controlled breeding in two ways: by extrapolation back from living breeds, and by analysis of ancient protein material. O f the latter, bone or tendon or skin collagens and hair keratins are the most perfectly preserved as molecular structures through 20000 years and indeed much longer. Amino acid sequences are expensive to determine (collagen has 1052 amino acid residues), and the potential of this palaeobiological information has been as yet little exploited. The first approach has, however, been more explored, in both plants and animals. Several protein systems must be studied in conjunction to reveal the phylogenetic threads in any one breed. As the three dimensional quaternary structure of protein molecules becomes more appreciated in relation to biological function, and as new techniques and procedures are developed, amino acid sequence data can become more informative in our ultimate understanding of early selective breeding.

scholarly journals Mammalian Surfactant Protein Homology by Domain Collagen Type IV: Evolutionary and Functional Analysis

2020 ◽  
pp. 19-23
Author(s):  
Kristina Bikmetova ◽  
Keyword(s):  
Amino Acid ◽  
Pulmonary Surfactant ◽  
Point Mutations ◽  
Surfactant Protein ◽  
Amino Acid Sequences ◽  
The Body ◽  
Essential Medicines ◽  
Collagen Type Iv ◽  
Alveolar Cells ◽  
Type Iv

The changes in the primary structures of proteins are strongly character due to evolution process. Some changes are beneficial and remain in the process of evolution, some ones are negatively affected to properties of the protein. Neutral changes in amino acid sequences can also occur, without affecting the protein and the body as a whole. Pulmonary surfactant is a surface-active lipoprotein complex (phospho-lipoprotein) formed by type II alveolar cells. The proteins and lipids that make up the surfactant have both hydrophilic and hydrophobic regions. As a medication, pulmonary surfactant is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system. The object of this study is surfactant-associated proteins. The aim of the study was to identify the relationship between the amino acid composition of the protein and its functions. The study of the structure of proteins was carried out using multiple alignment and building a phylogenetic tree. Proteins SP-A and SP-D are members of the C-type collectin family and consist of four domains: N-terminal sequence, collagen-like domain, carbohydrate recognition domain (CRD), “neck” between collagen-like and carbohydraterecognizing domains. Functionally, the most important are the C4 and CRD domains. Point mutations in these domains affect the change in the properties of proteins.

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