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Combining Protein Structures and Genomic Data Enhances Accuracy of Evolutionary Tree Analysis

Unlocking Ancient Evolutionary Secrets: How Protein Shapes Are Revolutionizing Phylogenetics

For decades, scientists⁤ have relied on genetic sequences to map the evolutionary relationships between species, a process known as phylogenetics. But now, groundbreaking research led ​by the Center‍ for⁢ Genomic Regulation (CRG) has unveiled a game-changing approach: using the three-dimensional shapes of proteins to resolve deep, ancient evolutionary relationships. This innovative method, dubbed “multistrap,” ⁤combines structural data with genomic sequences to enhance the reliability of evolutionary trees, offering new insights into the history of life and potential applications in disease ⁤treatment‍ and pathogen tracking.

The​ Challenge of Saturation in Phylogenetics ​

Traditional phylogenetic trees are built by comparing DNA⁢ or protein sequences, ‍identifying similarities and differences to infer relationships. Though, over ‍vast evolutionary timescales, a phenomenon called saturation occurs. As sequences‍ mutate extensively,they lose resemblance to their​ ancestral forms,erasing critical signals of shared ​heritage.“The issue of saturation dominates phylogeny and represents ‍the main obstacle for the reconstruction of ancient relationships,” explains Cedric Notredame, PhD, the study’s lead researcher. “It’s‍ like the erosion of an ancient text. The letters become indistinct, and the message is lost.”

To overcome this hurdle,the⁣ CRG team turned⁢ to protein ‍structures. Unlike sequences, which mutate rapidly, protein shapes are ⁤highly conserved⁢ over time, retaining ancestral features for longer periods. This resilience makes‍ them a powerful tool for resolving deep evolutionary nodes.

The Multistrap Approach: Bridging Structure and ⁢Sequence

The multistrap method leverages the ‌physical structures of proteins,‍ even those predicted by tools like AlphaFold 2, to construct more⁤ reliable phylogenetic trees. By measuring intra-molecular distances (IMDs)—the distances between pairs of amino⁤ acids ⁣within a protein—the researchers could quantify structural divergence over time. ⁢

“Our​ approach ⁢relies on the systematic comparison of⁣ homologous intra-molecular structural distances,” the team wrote in‌ their ⁢study, published in Nature communications. “We explore the potential of⁤ intramolecular distances to be treated as⁤ evolutionary characters and set out to ask if these ⁣characters could either help the reconstruction of phylogenetic trees​ or provide new ways of estimating branch reliability.”

The study​ compiled a massive dataset of proteins with⁢ known structures across⁣ a wide range of species. By ⁤calculating IMDs and ⁣constructing phylogenetic ‍trees, the researchers found‍ that structural data closely matched genetic sequence-based trees but with a significant advantage: structural trees were less affected by saturation, retaining ‌reliable signals even when sequences had diverged considerably.

Implications for evolutionary biology and Beyond

The implications of this​ research⁢ are profound. ⁤With 210,000⁤ experimentally persistent protein ⁣structures ⁢ and ⁢ 250 million ⁤known⁤ protein sequences, the‍ approach can⁣ be applied on‍ an unprecedented scale. ​Initiatives like the EarthBioGenome Project, which aims to​ sequence billions of⁣ genomes, will further expand the potential of this method.

“The resilience of⁣ protein folds⁢ is well established and has routinely been used to infer homology across evolutionary timespans incompatible with sequence analysis,” the authors noted. “This observation has⁤ led to the speculation that the quantitative comparison ⁢of protein folds could be used as ‍a metric to resolve deep nodes in phylogenetic trees.”

By integrating ‌structural ⁣data, scientists can now peer deeper into ‍the ancient history of​ life on Earth, uncovering relationships that were previously obscured by the limitations of sequence-based methods. This breakthrough also opens new avenues for understanding​ the spread of pathogens and developing ‌targeted treatments for diseases. ​

key Insights at⁣ a Glance

| Aspect ​ ⁤ ⁢ | Traditional Phylogenetics |⁣ Multistrap ‌Approach ‍ ‍ |
|—————————|——————————-|———————————-|
| Data ‌Source | DNA/protein sequences‍ ‌| Protein structures + sequences |
| Challenge ⁤ ⁤ | Saturation over time ⁤ | Less affected by saturation |
| Reliability ⁤ | Limited by sequence divergence| enhanced by⁢ structural ⁤conservation ‍|
| Applications | Evolutionary history | Pathogen tracking,⁣ disease treatment ⁣|

A New Era in Evolutionary Studies

The multistrap method represents a paradigm‌ shift in ‍phylogenetics, offering a ⁤more robust framework for reconstructing evolutionary relationships. As the scientific community continues to generate vast amounts of structural and sequence‌ data, this approach will undoubtedly play ⁤a pivotal⁤ role in unraveling the mysteries‍ of life’s ‍history.

For those eager to dive deeper‍ into ​the study, the‌ full paper, titled ⁣ “multistrap: boosting phylogenetic analyses with‌ structural information,” is⁣ available in Nature Communications. ⁣

This breakthrough not only ⁤enhances our understanding of evolution but also underscores the importance of interdisciplinary approaches in modern⁣ science. By bridging the gap between structural biology and‍ genomics, researchers are paving the way for ​discoveries that could‍ reshape our understanding⁤ of life itself.

A⁢ New ​Hybrid Approach⁢ to Phylogenetics: Combining‌ Sequences and Structures for Deeper Insights⁣

In a groundbreaking study, researchers have developed a novel hybrid⁤ method ​that combines ⁣ sequence and structure-based phylogenetic reconstructions to create more accurate evolutionary ⁤trees. This innovative approach, named multistrap, leverages the strengths of both data ‌types to improve the reliability of tree ​branches and distinguish ⁣between correct and incorrect relationships.

“Our results‍ show ​a significant level of congruence ‌between sequence ⁤and structure-based phylogenetic reconstructions,” the team explained.“We take advantage of this property ⁣to design a‌ hybrid bootstrap support method⁣ named multistrap, which combines sequence ⁤and structural information.”

Leila Mansouri,PhD,coauthor of ⁣the ⁢study,likened the method to having two witnesses describe an event from different angles. “Each‍ provides unique details, but together ⁣they give‌ a fuller, more accurate ⁢account,” ​she said.

Practical Applications: Kinases and Beyond

One area ‍where this combined approach could ⁣have a transformative impact is in understanding the relationships among kinases in the human genome. Kinases are proteins that play a critical role in regulating cellular functions, and their study is essential for advancing medical research.

“The genome of moast mammals, including ​humans, contains about 500 protein kinases that‌ regulate most aspects of our biology,” stated ⁢Notredame, a key contributor to the study. “These kinases are ⁤major⁤ targets for⁢ cancer therapy, for example drugs like imatinib for humans ​or toceranib for dogs.”

The implications of this research extend ⁢far beyond cancer treatment.by creating more accurate evolutionary trees,scientists can gain a deeper understanding of how diseases evolve,paving the way for the development of more effective vaccines and treatments. Additionally, ‌this approach can shed light on the origins of complex traits, guide the revelation of new enzymes for ‍ biotechnology, and even help trace the spread of species ⁤in ⁤response to climate change.‍

Key Insights at a Glance

| ⁢ Aspect ​ ​ ⁢ ⁢ | Details ⁢ ​ ⁣ ‌ ‍ ⁣ ⁢ ⁢ ​‍ |
|————————–|—————————————————————————–|
| Method ⁤ ⁤ | multistrap: A hybrid bootstrap‍ support method combining sequence and ⁢structural data. |
|‍ Primary Application | ‍Understanding relationships among kinases in the human‌ genome.|
| Impact on Medicine | Improved cancer therapies, vaccine development, and⁣ disease evolution insights. |
| Broader Applications | Biotechnology, climate change research,⁢ and ‍tracing species ⁢spread. ⁢ ⁣ ‌ |

Why This Matters

The integration of sequence‌ and structural data represents‍ a significant ‍leap ‌forward in phylogenetics. By combining these two perspectives, researchers can achieve a more extensive understanding of evolutionary ‍relationships, which​ is crucial for addressing ‍some of the most pressing challenges in‌ biology and medicine. ⁢

As an example, the ability to⁤ trace the evolution ⁢of diseases⁤ more accurately could revolutionize how we ​approach vaccine development and treatment strategies. Similarly, the ⁣discovery of new enzymes could open up exciting possibilities in biotechnology, from lasting manufacturing to environmental⁣ remediation.

A Call to Action

As this⁢ research continues to ⁣unfold, it’s clear that the potential applications ⁢are⁢ vast and far-reaching.Weather you’re a​ scientist, a medical professional, or simply someone interested ⁢in the​ cutting edge ‍of​ biology,​ staying informed about advancements like multistrap ⁣is essential. Dive deeper into the world of phylogenetics and explore how⁣ this hybrid approach is shaping the future⁢ of science.

By embracing this dual-outlook ⁣methodology, we’re not just improving our ⁤understanding of the​ past—we’re‌ paving the way for a healthier, more sustainable future.

Unlocking Ancient Evolutionary⁣ Secrets: How‍ Protein Shapes Are Revolutionizing‍ Phylogenetics

For decades, scientists ⁢have relied on ‌genetic ​sequences to map the evolutionary relationships between species, a ‌process known‌ as phylogenetics. However, groundbreaking‌ research ⁢led ⁤by the Center for⁣ Genomic Regulation (CRG) has unveiled a game-changing approach: using the three-dimensional shapes ⁣of ‌proteins to⁢ resolve deep, ancient evolutionary relationships. This innovative method, dubbed “multistrap,” combines structural data with genomic sequences to enhance the reliability of evolutionary trees, offering new insights into the history of life ⁢and potential applications in disease treatment and pathogen⁣ tracking.


The Challenge of Saturation in Phylogenetics

Conventional phylogenetic trees are built by comparing DNA or protein⁣ sequences, identifying similarities and‍ differences to infer relationships. However, over vast evolutionary timescales,‍ a phenomenon called saturation occurs.‍ As sequences mutate extensively, thay lose resemblance to their ancestral forms, erasing critical signals of shared heritage.

“The issue of saturation dominates phylogeny and⁤ represents the main ⁤obstacle for the reconstruction of ancient relationships,” explains Cedric Notredame, PhD, the study’s lead researcher. “It’s like the erosion of an ancient text. The letters become indistinct,⁤ and ​the message ​is ​lost.”

To overcome this hurdle, ‌the CRG team ⁣turned to protein ‍structures. ‍Unlike sequences, which mutate rapidly, protein shapes are highly conserved over time, retaining ancestral features for longer periods. This ‌resilience makes⁤ them a powerful tool for resolving deep⁢ evolutionary nodes.


The Multistrap ⁢Approach: Bridging structure and Sequence

The‌ multistrap method leverages the physical structures of proteins, even those​ predicted by tools like ​ AlphaFold 2, to construct more reliable ⁣phylogenetic trees. By measuring intra-molecular distances (IMDs)—the distances between pairs of amino acids within​ a ⁣protein—the ⁢researchers could⁣ quantify‌ structural divergence over time.

“Our approach relies on the systematic comparison of homologous intra-molecular ‌structural distances,” the team wrote in their study, published in Nature Communications. “We explore the potential of intramolecular distances to be treated ‌as evolutionary ⁣characters and set out to ask‌ if these characters could either help the reconstruction of phylogenetic trees or provide new ways of estimating branch reliability.”

The study compiled ⁣a ‌massive dataset of proteins with known structures across a wide ​range of species. By calculating IMDs and constructing phylogenetic trees, the researchers found that structural ​data closely matched genetic sequence-based trees but with a meaningful advantage: structural trees ⁢were less affected by​ saturation, retaining reliable signals even when sequences had diverged considerably.


Implications for Evolutionary‍ Biology⁤ and Beyond

The implications of this research are profound. With 210,000‍ experimentally persistent protein structures and 250 million known protein sequences, the approach ⁢can ⁤be applied on an ‌unprecedented scale. Initiatives‌ like the EarthBioGenome Project, which ​aims to sequence billions ‌of genomes, will further expand the potential of this method. ⁤

“The resilience of protein folds is well established and has routinely been used to infer homology across evolutionary timespans incompatible with sequence analysis,” the authors noted. “This ⁣observation⁤ has led to the speculation that ‌the quantitative⁣ comparison of protein folds could be used as a metric to resolve deep nodes in phylogenetic trees.”

By integrating structural data,‌ scientists can now peer deeper into the ancient history of life on earth, uncovering relationships‌ that ‌were previously obscured by the limitations of sequence-based methods. This breakthrough also opens new avenues for understanding the spread of pathogens and developing targeted ‍treatments for⁤ diseases.


Key Insights at a Glance

| ⁤ Aspect ​ | Traditional Phylogenetics | ⁤ Multistrap Approach ​ ​ ⁤|

|—————————|——————————-|———————————-| ‌

| Data Source | DNA/protein sequences ⁤ | Protein structures + sequences |

| Challenge ​⁢ ‍ ‍ | Saturation over time ⁣ | Less affected by saturation⁢ |

| Reliability | Limited by⁢ sequence divergence| Enhanced by structural conservation |

| Applications | Evolutionary history ‌ ⁤ ⁣ | Pathogen tracking, disease ​treatment |


A New Era in Evolutionary Studies

The ‍ multistrap ​method represents a paradigm shift in phylogenetics, offering a more robust framework for‍ reconstructing evolutionary relationships. As the ⁢scientific community continues to generate ⁢vast amounts of structural and sequence data,‍ this approach will​ undoubtedly play a pivotal role in unraveling the mysteries of​ life’s ⁢history.

For those eager to dive ⁤deeper into ​the study, the full paper, titled “multistrap: boosting phylogenetic analyses with structural facts,” is available in ⁣ Nature⁤ Communications.

This breakthrough not⁤ only enhances our understanding of evolution but also underscores the importance of interdisciplinary approaches in modern science. By bridging⁣ the gap ‌between structural biology and genomics, researchers are paving the way for⁢ discoveries that ⁤could reshape our understanding of life itself.


A ‍New Hybrid Approach to​ Phylogenetics: Combining Sequences ​and Structures for Deeper Insights

in a groundbreaking study, researchers have developed a novel⁢ hybrid method that combines sequence and structure-based phylogenetic reconstructions to create more‌ accurate evolutionary trees. This innovative approach, named multistrap, leverages the strengths of both data types to improve the reliability of tree branches ​and distinguish between correct and incorrect‌ relationships.

“Our results show a significant level of congruence between sequence and structure-based phylogenetic reconstructions,” the team explained.“We ⁤take advantage of this property to design​ a hybrid bootstrap support method named multistrap, which ⁣combines sequence and structural information.”

Leila Mansouri, PhD, coauthor of the study, likened the method to having two witnesses describe an ⁣event from different angles. “Each provides unique details, but together they ‍give a fuller, more accurate account,” she said.


Practical Applications: Kinases and Beyond

One area were this⁣ combined approach could have a transformative impact is in understanding‌ the relationships among kinases in ‌the human genome. Kinases⁣ are proteins that play a critical role in cellular signaling and are often implicated in diseases such as cancer. By applying the multistrap method, researchers can gain deeper insights ⁣into the evolutionary history of kinases, perhaps ⁢uncovering new therapeutic targets and improving⁢ our understanding of disease mechanisms.

This ⁢hybrid ⁤approach not only​ enhances the accuracy of phylogenetic reconstructions but also opens ‍up new possibilities for studying other protein ⁤families and their roles in evolution, health, and disease.

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