Darwin, nós temos um problema: expondo os pontos fracos evolutivos do genoma humano

sexta-feira, setembro 23, 2022

Extreme purifying selection against point mutations in the human genome

Noah Dukler, Mehreen R. Mughal, Ritika Ramani, Yi-Fei Huang & Adam Siepel 

Nature Communications volume 13, Article number: 4312 (2022)


Large-scale genome sequencing has enabled the measurement of strong purifying selection in protein-coding genes. Here we describe a new method, called ExtRaINSIGHT, for measuring such selection in noncoding as well as coding regions of the human genome. ExtRaINSIGHT estimates the prevalence of “ultraselection” by the fractional depletion of rare single-nucleotide variants, after controlling for variation in mutation rates. Applying ExtRaINSIGHT to 71,702 whole genome sequences from gnomAD v3, we find abundant ultraselection in evolutionarily ancient miRNAs and neuronal protein-coding genes, as well as at splice sites. By contrast, we find much less ultraselection in other noncoding RNAs and transcription factor binding sites, and only modest levels in ultraconserved elements. We estimate that ~0.4–0.7% of the human genome is ultraselected, implying ~ 0.26–0.51 strongly deleterious mutations per generation. Overall, our study sheds new light on the genome-wide distribution of fitness effects by combining deep sequencing data and classical theory from population genetics.

RNA, o epicentro de informação genética

terça-feira, setembro 20, 2022

RNA, the Epicenter of Genetic Information

By John Mattick, Paulo Amaral

Copyright Year 2023 ISBN 9780367567781

Published September 20, 2022 by CRC Press

422 Pages 78 Color & 23 B/W Illustrations

Available on Taylor & Francis eBooks

Book Description

The origin story and emergence of molecular biology is muddled. The early triumphs in bacterial genetics and the complexity of animal and plant genomes complicate an intricate history. This book documents the many advances, as well as the prejudices and founder fallacies. It highlights the premature relegation of RNA to simply an intermediate between gene and protein, the underestimation of the amount of information required to program the development of multicellular organisms, and the dawning realization that RNA is the cornerstone of cell biology, development, brain function and probably evolution itself. Key personalities, their hubris as well as prescient predictions are richly illustrated with quotes, archival material, photographs, diagrams and references to bring the people, ideas and discoveries to life, from the conceptual cradles of molecular biology to the current revolution in the understanding of genetic information.

Key Features

- Documents the confused early history of DNA, RNA and proteins - a transformative history of molecular biology like no other.

- Integrates the influences of biochemistry and genetics on the landscape of molecular biology.

- Chronicles the important discoveries, preconceptions and misconceptions that retarded or misdirected progress.

- Highlights major pioneers and contributors to molecular biology, with a focus on RNA and noncoding DNA.

- Summarizes the mounting evidence for the central roles of non-protein-coding RNA in cell and developmental biology.

- Provides a thought-provoking retrospective and forward-looking perspective for advanced students and professional researchers.

The Open Access version of this book, available at www.taylorfrancis.com, has been made available under a Creative Commons Attribution-Non Commercial-No Derivatives 4.0 license.


Nomenklatura científica, nós temos um problema: diminuindo a Navalha de Ockham!

terça-feira, setembro 13, 2022

Cutting Down Ockham's Razor

William of Ockham famously argued that the simplest explanation is likely the best one. The idea is appealing, widely believed, and deeply misleading.

By Jim Al-Khalili

 Save your razors for shaving hairs Image/Imagem

We hear all the time that the simplest explanations are usually the right ones. This truth-testing idea—known as Ockham’s razor, after the English medieval philosopher William of Ockham—has been embraced by no less authorities than Isaac Newton and Albert Einstein. Today scientists invoke Ockham’s razor on topics ranging from Covid’s origins to cosmic dark matter, while folks debating a subject on social media regularly invoke it as their final arbiter. After all, why complicate something more than you need to? Isn’t it better to shave ideas down to their essential truths?

Ockham’s razor sounds logical and definitive, which is exactly what makes it dangerous. Not only is the assumption of simplicity often false, but following it blindly can lead to serious misunderstandings, both in science and in everyday life.

A well-known historical validation of the principle of simplicity in science was in the overthrow of the geocentric model of the universe. The ancient Greeks codified a cosmology in which Earth was motionless while the sun, moon, planets, and stars all moved around it in perfect circular paths. That model held sway for nearly 2,000 years, despite becoming increasingly cumbersome as it was modified to account for the observed movements of planets like Mars, which was seen to slow down, speed up, and sometimes even double back on itself.

The Greeks attempted to account for this “retrograde” motion of Mars by assuming that it followed a secondary, smaller circular path, called an epicycle, that was bolted onto its primary circular motion around Earth. Later, improved observations of Mars and the other planets required further tinkering with the geocentric model, such as adding epicycles on top of epicycles and shifting Earth slightly away from the center of all the other bodies’ orbits.

Then, in the 16th century, Nicolaus Copernicus swept away this makeshift model and replaced it with his much simpler heliocentric picture in which the sun, not Earth, is at the center of the universe. In this view, the complicated motions of Mars as seen from Earth could be explained as a consequence of the two planets orbiting the sun at different distances and speeds. Both the Earth-centered and sun-centered models worked, in the sense that they predicted the motions of heavenly bodies reasonably well, but we now know that only one of them is correct: the Copernican model, the one without all the clumsy extras. This, we are told, is Ockham’s razor in action.

But the above account is wrong. Although Copernicus correctly replaced Earth with the sun at the center of the known cosmos, he still believed the planetary orbits to be perfect circles rather than their actual ellipses. As a result, he still needed the epicycles and other unwieldy patch-ups of the old geocentric model to get this heliocentric system to work. Although we now know that Earth does indeed go around the sun, we also know that the true dynamics of our solar system are far more convoluted than anything the ancient Greeks could have imagined. In place of epicycles, we have an ever-shifting system of ellipses whose shapes can never be calculated with perfect precision. It is Ockham’s razor in reverse.

An equally famous example in the history of science is Darwin’s theory of evolution through natural selection. It provides a unifying explanation for the tremendous variety of life we find on Earth, all of which evolved over billions of years from a single origin. Darwin’s theory is based on a few simple assumptions: 1) that individuals within a population of any species vary; 2) that these variations pass down through the generations; 3) that more individuals are born in each generation than can survive; 4) that those with characteristics better adapted to suit their environment are more likely to survive and reproduce. That’s it.

However, wrapped up in these modest assumptions are the mind-bogglingly complex fields of evolutionary biology and genetics, which are among the most challenging areas in all of science. If we are to truly apply Ockham’s razor to life on Earth, then surely the nonscientific theory of creationism—that all life was brought forth as it is today by a supernatural maker—is far simpler than Darwinian evolution.


Read more/Leia mais: Open Mind Magazine