scholarly journals Were Ancestral Proteins Less Specific?

2021 ◽  
Author(s):  
Lucas C Wheeler ◽  
Michael J Harms
Keyword(s):  
Common Ancestor ◽  
Last Common Ancestor ◽  
Random Set ◽  
Ancestral Reconstruction ◽  
Cautionary Note ◽  
Biological Targets ◽  
Peptide Binding Specificity ◽  
Lower Specificity ◽  
Biological Specificity ◽  
Sequence Reconstruction

Abstract Some have hypothesized that ancestral proteins were, on average, less specific than their descendants. If true, this would provide a universal axis along which to organize protein evolution and suggests that reconstructed ancestral proteins may be uniquely powerful tools for protein engineering. Ancestral sequence reconstruction studies are one line of evidence used to support this hypothesis. Previously, we performed such a study, investigating the evolution of peptide-binding specificity for the paralogs S100A5 and S100A6. The modern proteins appeared more specific than their last common ancestor (ancA5/A6), as each paralog bound a subset of the peptides bound by ancA5/A6. In this study, we revisit this transition, using quantitative phage display to measure the interactions of 30,533 random peptides with human S100A5, S100A6, and ancA5/A6. This unbiased screen reveals a different picture. While S100A5 and S100A6 do indeed bind to a subset of the peptides recognized by ancA5/A6, they also acquired new peptide partners outside of the set recognized by ancA5/A6. Our previous work showed that ancA5/A6 had lower specificity than its descendants when measured against biological targets; our new work shows that ancA5/A6 has similar specificity to the modern proteins when measured against a random set of peptide targets. This demonstrates that altered biological specificity does not necessarily indicate altered intrinsic specificity, and sounds a cautionary note for using ancestral reconstruction studies with biological targets as a means to infer global evolutionary trends in specificity.

scholarly journals Were ancestral proteins less specific?

2020 ◽  
Author(s):  
Lucas C. Wheeler ◽  
Michael J. Harms
Keyword(s):  
Common Ancestor ◽  
Last Common Ancestor ◽  
Random Set ◽  
Ancestral Reconstruction ◽  
Cautionary Note ◽  
Biological Targets ◽  
Peptide Binding Specificity ◽  
Lower Specificity ◽  
Biological Specificity ◽  
Sequence Reconstruction

AbstractSome have hypothesized that ancestral proteins were, on average, less specific than their descendants. If true, this would provide a universal axis along which to organize protein evolution and suggests that reconstructed ancestral proteins may be uniquely powerful tools for protein engineering. Ancestral sequence reconstruction studies are one line of evidence used to support this hypothesis. Previously, we performed such a study, investigating the evolution of peptide binding specificity for the paralogs S100A5 and S100A6. The modern proteins appeared more specific than their last common ancestor (ancA5/A6), as each paralog bound a subset of the peptides bound by ancA5/A6. In the current study, we revisit this transition, using quantitative phage display to measure the interactions of 19,194 random peptides with human S100A5, S100A6, and ancA5/A6. This unbiased screen reveals a different picture. While S100A5 and S100A6 do indeed bind to a subset of the peptides recognized by ancA5/A6, they also acquired new peptide partners outside of the set recognized by ancA5/A6. Our previous work showed that ancA5/A6 had lower specificity than its descendants when measured against biological targets; our new work shows that ancA5/A6 has similar specificity to the modern proteins when measured against a random set of peptide targets. This demonstrates that altered biological specificity does not necessarily indicate altered intrinsic specificity, and sounds a cautionary note for using ancestral reconstruction studies with biological targets as a means to infer global evolutionary trends in specificity.

scholarly journals Conservation of specificity in two low-specificity protein

2017 ◽  
Author(s):  
Lucas C. Wheeler ◽  
Jeremy A. Anderson ◽  
Anneliese J. Morrison ◽  
Caitlyn E. Wong ◽  
Michael J. Harms
Keyword(s):  
Peptide Binding ◽  
Binding Specificity ◽  
Titration Calorimetry ◽  
Last Common Ancestor ◽  
Linear Peptide ◽  
Peptide Binding Specificity ◽  
Binding Interface ◽  
Sequence Reconstruction ◽  
Biochemical Approach ◽  
Specificity Protein

AbstractS100 proteins bind linear peptide regions of target proteins and modulate their activity. The peptide binding interface, however, has remarkably low specificity and can interact with many target peptides. It is not clear if the interface discriminates targets in a biological context, or whether biological specificity is achieved exclusively through external factors such as subcellular localization. To discriminate these possibilities, we used an evolutionary biochemical approach to trace the evolution of paralogs S100A5 and S100A6. We first used isothermal titration calorimetry to study the binding of a collection of peptides with diverse sequence, hydrophobicity, and charge to human S100A5 and S100A6. These proteins bound distinct, but overlapping, sets of peptide targets. We then studied the peptide binding properties of S100A5 and S100A6 orthologs sampled from across five representative amniote species. We found that the pattern of binding specificity was conserved along all lineages, for the last 320 million years, despite the low specificity of each protein. We next used Ancestral Sequence Reconstruction to determine the binding specificity of the last common ancestor of the paralogs. We found the ancestor bound the whole set of peptides bound by modern S100A5 and S100A6 proteins, suggesting that paralog specificity evolved by subfunctionalization. To rule out the possibility that specificity is conserved because it is difficult to modify, we identified a single historical mutation that, when reverted in human S100A5, gave it the ability to bind an S100A6-specific peptide. These results indicate that there are strong evolutionary constraints on peptide binding specificity, and that, despite being able to bind a large number of targets, the specificity of S100 peptide interfaces is indeed important for the biology of these proteins.

scholarly journals Ancestral Reconstruction and Investigations of Genomic Recombination on some Pentapetalae Chloroplasts

2019 ◽  
Vol 16 (4) ◽  
Author(s):  
Christophe Guyeux ◽  
Michel Salomon ◽  
Bashar Al-Nuaimi ◽  
Bassam AlKindy ◽  
Jean-François Couchot
Keyword(s):  
Pattern Matching ◽  
Common Ancestor ◽  
Last Common Ancestor ◽  
Ancestral Reconstruction ◽  
Matching Method ◽  
Order Analysis ◽  
Naked Eye ◽  
Automated Method ◽  
Series Of Experiments ◽  
Genomic Recombination

AbstractIn this article, we propose a semi-automated method to rebuild genome ancestors of chloroplasts by taking into account gene duplication. Two methods have been used in order to achieve this work: a naked eye investigation using homemade scripts, whose results are considered as a basis of knowledge, and a dynamic programming based approach similar to Needleman-Wunsch. The latter fundamentally uses the Gestalt pattern matching method of sequence matcher to evaluate the occurrences probability of each gene in the last common ancestor of two given genomes. The two approaches have been applied on chloroplastic genomes from Apiales, Asterales, and Fabids orders, the latter belonging to Pentapetalae group. We found that Apiales species do not undergo indels, while they occur in the Asterales and Fabids orders. A series of experiments was then carried out to extensively verify our findings by comparing the obtained ancestral reconstruction results with the latest released approach called MLGO (Maximum Likelihood for Gene-Order analysis).

Engineering ancestral protein hyperstability

2016 ◽  
Vol 473 (20) ◽  
pp. 3611-3620 ◽  
Author(s):  
M. Luisa Romero-Romero ◽  
Valeria A. Risso ◽  
Sergio Martinez-Rodriguez ◽  
Beatriz Ibarra-Molero ◽  
Jose M. Sanchez-Ruiz
Keyword(s):  
Common Ancestor ◽  
A Priori ◽  
Experimental Comparison ◽  
Last Common Ancestor ◽  
Ancestral Reconstruction ◽  
Denaturation Temperature ◽  
General Applicability ◽  
Reconstruction Process ◽  
Ancestral Sequences ◽  
Protein Properties

Many experimental analyses and proposed scenarios support that ancient life was thermophilic. In congruence with this hypothesis, proteins encoded by reconstructed sequences corresponding to ancient phylogenetic nodes often display very high stability. Here, we show that such ‘reconstructed ancestral hyperstability’ can be further engineered on the basis of a straightforward approach that uses exclusively information afforded by the ancestral reconstruction process itself. Since evolution does not imply continuous progression, screening of the mutations between two evolutionarily related resurrected ancestral proteins may identify mutations that further stabilize the most stable one. To explore this approach, we have used a resurrected thioredoxin corresponding to the last common ancestor of the cyanobacterial, Deinococcus and Thermus groups (LPBCA thioredoxin), which has a denaturation temperature of ∼123°C. This high value is within the top 0.1% of the denaturation temperatures in the ProTherm database and, therefore, achieving further stabilization appears a priori as a challenging task. Nevertheless, experimental comparison with a resurrected thioredoxin corresponding to the last common ancestor of bacteria (denaturation temperature of ∼115°C) immediately identifies three mutations that increase the denaturation temperature of LPBCA thioredoxin to ∼128°C. Comparison between evolutionarily related resurrected ancestral proteins thus emerges as a simple approach to expand the capability of ancestral reconstruction to search sequence space for extreme protein properties of biotechnological interest. The fact that ancestral sequences for many phylogenetic nodes can be derived from a single alignment of modern sequences should contribute to the general applicability of this approach.

scholarly journals The molecular signal for the adaptation to cold temperature during early life on Earth

2013 ◽  
Vol 9 (5) ◽  
pp. 20130608 ◽  
Author(s):  
Mathieu Groussin ◽  
Bastien Boussau ◽  
Sandrine Charles ◽  
Samuel Blanquart ◽  
Manolo Gouy
Keyword(s):  
Phylogenetic Trees ◽  
Large Scale ◽  
Common Ancestor ◽  
Phylogenetic Signal ◽  
Optimal Growth ◽  
Ancestral Sequence ◽  
Rate Variation ◽  
Last Common Ancestor ◽  
Ancestral Sequence Reconstruction ◽  
Sequence Reconstruction

Several lines of evidence such as the basal location of thermophilic lineages in large-scale phylogenetic trees and the ancestral sequence reconstruction of single enzymes or large protein concatenations support the conclusion that the ancestors of the bacterial and archaeal domains were thermophilic organisms which were adapted to hot environments during the early stages of the Earth. A parsimonious reasoning would therefore suggest that the last universal common ancestor (LUCA) was also thermophilic. Various authors have used branch-wise non-homogeneous evolutionary models that better capture the variation of molecular compositions among lineages to accurately reconstruct the ancestral G + C contents of ribosomal RNAs and the ancestral amino acid composition of highly conserved proteins. They confirmed the thermophilic nature of the ancestors of Bacteria and Archaea but concluded that LUCA, their last common ancestor, was a mesophilic organism having a moderate optimal growth temperature. In this letter, we investigate the unknown nature of the phylogenetic signal that informs ancestral sequence reconstruction to support this non-parsimonious scenario. We find that rate variation across sites of molecular sequences provides information at different time scales by recording the oldest adaptation to temperature in slow-evolving regions and subsequent adaptations in fast-evolving ones.

scholarly journals Experimental evidence for yawn contagion in orangutans (Pongo pygmaeus)

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Evy van Berlo ◽  
Alejandra P. Díaz-Loyo ◽  
Oscar E. Juárez-Mora ◽  
Mariska E. Kret ◽  
Jorg J. M. Massen
Keyword(s):  
Experimental Evidence ◽  
Common Ancestor ◽  
Great Apes ◽  
Pongo Pygmaeus ◽  
Last Common Ancestor ◽  
Contagious Yawning ◽  
Proximate Mechanism ◽  
Social Species ◽  
Ultimate Causation

AbstractYawning is highly contagious, yet both its proximate mechanism(s) and its ultimate causation remain poorly understood. Scholars have suggested a link between contagious yawning (CY) and sociality due to its appearance in mostly social species. Nevertheless, as findings are inconsistent, CY’s function and evolution remains heavily debated. One way to understand the evolution of CY is by studying it in hominids. Although CY has been found in chimpanzees and bonobos, but is absent in gorillas, data on orangutans are missing despite them being the least social hominid. Orangutans are thus interesting for understanding CY’s phylogeny. Here, we experimentally tested whether orangutans yawn contagiously in response to videos of conspecifics yawning. Furthermore, we investigated whether CY was affected by familiarity with the yawning individual (i.e. a familiar or unfamiliar conspecific and a 3D orangutan avatar). In 700 trials across 8 individuals, we found that orangutans are more likely to yawn in response to yawn videos compared to control videos of conspecifics, but not to yawn videos of the avatar. Interestingly, CY occurred regardless of whether a conspecific was familiar or unfamiliar. We conclude that CY was likely already present in the last common ancestor of humans and great apes, though more converging evidence is needed.

scholarly journals Recombinant transfer in the basic genome ofEscherichia coli

2015 ◽  
Vol 112 (29) ◽  
pp. 9070-9075 ◽  
Author(s):  
Purushottam D. Dixit ◽  
Tin Yau Pang ◽  
F. William Studier ◽  
Sergei Maslov
Keyword(s):  
Common Ancestor ◽  
Recipient Cell ◽  
Gene Clusters ◽  
Selective Advantage ◽  
Last Common Ancestor ◽  
Genome Sequences ◽  
Bacterial Genomes ◽  
Basic Genome ◽  
Single Base Pair ◽  
Generalized Transduction

An approximation to the ∼4-Mbp basic genome shared by 32 strains ofEscherichia colirepresenting six evolutionary groups has been derived and analyzed computationally. A multiple alignment of the 32 complete genome sequences was filtered to remove mobile elements and identify the most reliable ∼90% of the aligned length of each of the resulting 496 basic-genome pairs. Patterns of single base-pair mutations (SNPs) in aligned pairs distinguish clonally inherited regions from regions where either genome has acquired DNA fragments from diverged genomes by homologous recombination since their last common ancestor. Such recombinant transfer is pervasive across the basic genome, mostly between genomes in the same evolutionary group, and generates many unique mosaic patterns. The six least-diverged genome pairs have one or two recombinant transfers of length ∼40–115 kbp (and few if any other transfers), each containing one or more gene clusters known to confer strong selective advantage in some environments. Moderately diverged genome pairs (0.4–1% SNPs) show mosaic patterns of interspersed clonal and recombinant regions of varying lengths throughout the basic genome, whereas more highly diverged pairs within an evolutionary group or pairs between evolutionary groups having >1.3% SNPs have few clonal matches longer than a few kilobase pairs. Many recombinant transfers appear to incorporate fragments of the entering DNA produced by restriction systems of the recipient cell. A simple computational model can closely fit the data. Most recombinant transfers seem likely to be due to generalized transduction by coevolving populations of phages, which could efficiently distribute variability throughout bacterial genomes.

Improved resolution of recalcitrant nodes in the animal phylogeny through the analysis of genome gene content and morphology

2021 ◽  
Author(s):  
Ksenia Juravel ◽  
Luis Porras ◽  
Sebastian Hoehna ◽  
Davide Pisani ◽  
Gert Wörheide
Keyword(s):  
Common Ancestor ◽  
Sister Group ◽  
The Other ◽  
Gene Content ◽  
Statistical Hypothesis ◽  
Phylogenetic Position ◽  
Last Common Ancestor ◽  
Statistical Hypothesis Testing ◽  
Animal Phylogeny ◽  
Phylogenetic Hypotheses

An accurate phylogeny of animals is needed to clarify their evolution, ecology, and impact on shaping the biosphere. Although multi-gene alignments of up to several hundred thousand amino acids are nowadays routinely used to test hypotheses of animal relationships, some nodes towards the root of the animal phylogeny are proving hard to resolve. While the relationships of the non-bilaterian lineages, primarily sponges (Porifera) and comb jellies (Ctenophora), have received much attention since more than a decade, controversies about the phylogenetic position of the worm-like bilaterian lineage Xenacoelomorpha and the monophyly of the "Superphylum" Deuterostomia have more recently emerged. Here we independently analyse novel genome gene content and morphological datasets to assess patterns of phylogenetic congruence with previous amino-acid derived phylogenetic hypotheses. Using statistical hypothesis testing, we show that both our datasets very strongly support sponges as the sister group of all the other animals, Xenoacoelomorpha as the sister group of the other Bilateria, and largely support monophyletic Deuterostomia. Based on these results, we conclude that the last common animal ancestor may have been a simple, filter-feeding organism without a nervous system and muscles, while the last common ancestor of Bilateria might have been a small, acoelomate-like worm without a through gut.

Inductive patterning of the embryonic brain in Drosophila

Development ◽  
2002 ◽  
Vol 129 (9) ◽  
pp. 2121-2128
Author(s):  
Damon T. Page
Keyword(s):  
Brain Development ◽  
Common Ancestor ◽  
Last Common Ancestor ◽  
Embryonic Brain ◽  
Germ Layers ◽  
Brain Anomaly ◽  
Prechordal Plate ◽  
Foregut Endoderm ◽  
The Brain ◽  
Brain Patterning

In vertebrates (deuterostomes), brain patterning depends on signals from adjacent tissues. For example, holoprosencephaly, the most common brain anomaly in humans, results from defects in signaling between the embryonic prechordal plate (consisting of the dorsal foregut endoderm and mesoderm) and the brain. I have examined whether a similar mechanism of brain development occurs in the protostome Drosophila, and find that the foregut and mesoderm act to pattern the fly embryonic brain. When the foregut and mesoderm of Drosophila are ablated, brain patterning is disrupted. The loss of Hedgehog expressed in the foregut appears to mediate this effect, as it does in vertebrates. One mechanism whereby these defects occur is a disruption of normal apoptosis in the brain. These data argue that the last common ancestor of protostomes and deuterostomes had a prototype of the brains present in modern animals, and also suggest that the foregut and mesoderm contributed to the patterning of this ‘proto-brain’. They also argue that the foreguts of protostomes and deuterostomes, which have traditionally been assigned to different germ layers, are actually homologous.

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