Últimos 5.000 anos prolíficos para mudanças no genoma humano

quinta-feira, novembro 29, 2012

Past 5,000 years prolific for changes to human genome

High-resolution sequencing study emphasizes importance of rare variants in disease.

Nidhi Subbaraman

28 November 2012

The human genome has been busy over the past 5,000 years. Human populations have grown exponentially, and new genetic mutations arise with each generation. Humans now have a vast abundance of rare genetic variants in the protein-encoding sections of the genome 1, 2.

A study published today in Nature 3 now helps to clarify when many of those rare variants arose. Researchers used deep sequencing to locate and date more than one million single-nucleotide variants — locations where a single letter of the DNA sequence is different from other individuals — in the genomes of 6,500 African and European Americans. The findings confirm their earlier work suggesting that the majority of variants, including potentially harmful ones, were picked up during the past 5,000–10,000 years. Researchers also saw the genetic stamp of the diverging migratory history of the two groups.

Humans are carrying around more harmful mutations in the last 5,000 years.

The large sample size — 4,298 North Americans of European descent and 2,217 African Americans — has enabled the researchers to mine down into the human genome, says study co-author Josh Akey, a genomics expert at the University of Washington in Seattle. He adds that the researchers now have “a way to look at recent human history in a way that we couldn’t before.”

Read more here/Leia mais aqui: Nature

DNA: o disco rígido final

quarta-feira, novembro 28, 2012

DNA: The Ultimate Hard Drive
by John Bohannon on 16 August 2012, 2:10 PM

When it comes to storing information, hard drives don't hold a candle to DNA. Our genetic code packs billions of gigabytes into a single gram. A mere milligram of the molecule could encode the complete text of every book in the Library of Congress and have plenty of room to spare. All of this has been mostly theoretical—until now. In a new study, researchers stored an entire genetics textbook in less than a picogram of DNA—one trillionth of a gram—an advance that could revolutionize our ability to save data.
Credit: Sergey Volkov/iStockphoto

A few teams have tried to write data into the genomes of living cells. But the approach has a couple of disadvantages. First, cells die—not a good way to lose your term paper. They also replicate, introducing new mutations over time that can change the data.
To get around these problems, a team led by George Church, a synthetic biologist at Harvard Medical School in Boston, created a DNA information-archiving system that uses no cells at all. Instead, an inkjet printer embeds short fragments of chemically synthesized DNA onto the surface of a tiny glass chip. To encode a digital file, researchers divide it into tiny blocks of data and convert these data not into the 1s and 0s of typical digital storage media, but rather into DNA’s four-letter alphabet of As, Cs, Gs, and Ts. Each DNA fragment also contains a digital "barcode" that records its location in the original file. Reading the data requires a DNA sequencer and a computer to reassemble all of the fragments in order and convert them back into digital format. The computer also corrects for errors; each block of data is replicated thousands of times so that any chance glitch can be identified and fixed by comparing it to the other copies.
Read more here/Leia mais aqui: Science Now
Os cientistas, apesar do Projeto Genoma, nada sabem sobre a origem do DNA, a não um punhado de especulações carentes de corroboração em um contexto de justificação teórica por ser um aspecto de ciência histórica...

Mais uma teoria sobre a origem da vida: Conjuntos autocatalíticos...

segunda-feira, novembro 26, 2012

Acta Biotheoretica

December 2012, Volume 60, Issue 4, pp 379-392

The Structure of Autocatalytic Sets: Evolvability, Enablement, and Emergence

Wim Hordijk, Mike Steel, Stuart Kauffman

Image not related to this article/Imagem não relacionada a este artigo


This paper presents new results from a detailed study of the structure of autocatalytic sets. We show how autocatalytic sets can be decomposed into smaller autocatalytic subsets, and how these subsets can be identified and classified. We then argue how this has important consequences for the evolvability, enablement, and emergence of autocatalytic sets. We end with some speculation on how all this might lead to a generalized theory of autocatalytic sets, which could possibly be applied to entire ecologies or even economies.


Payment or subscription needed/Necessário pagamento ou assinatura: 

A arquitetura revela os segredos do genoma

Architecture Reveals Genome’s Secrets

Three-dimensional genome maps are leading to a deeper understanding of how the genome’s form influences its function.

Human chromosome - Hans Ris

By Sabrina Richards | November 25, 2012

Genome sequencing projects have provided rich troves of information about stretches of DNA that regulate gene expression, as well as how different genetic sequences contribute to health and disease. But these studies misses a key element of the genome—its spatial organization—which has long been recognized as an important regulator of gene expression. Regulatory elements often lie thousands of base pairs away from their target genes, and recent technological advances are allowing scientists to begin examining how distant chromosome locations interact inside a nucleus.  The creation and function of 3-D genome organization, some say, is the next frontier of genetics.
Genome spatial organization is critical for gene regulation, explained Job Dekker, a molecular geneticist at the University of Massachusetts Medical School, and “everything else chromosomes do involves three dimensions,” as well. Chromosomes have to replicate, separate properly during division, and change shape during the cell cycle—all without tangling. The genome is “rebuilt entirely after cell division,” Dekker said.
The mechanisms for such delicate orchestration have remained unclear, however. About 10 years ago—just as the human genome project was completing its first draft sequence—Dekker pioneered a new technique, called chromosome conformation capture (C3) that allowed researchers to get a glimpse of how chromosomes are arranged relative to each other in the nucleus. The technique relies on the physical cross-linking of chromosomal regions that lie in close proximity to one another. The regions are then sequenced to identify which regions have been cross-linked. In 2009, using a high throughput version of this basic method, called HiC, Dekker and his collaborators discovered that the human genome appears to adopt a “fractal globule” conformation—a manner of crumpling without knotting.
In the last 3 years, Dekker and others have advanced technology even further, allowing them to paint a more refined picture of how the genome folds—and how this influences gene expression and disease states.
Conversing chromosomes
Dekker’s 2009 findings were a breakthrough in modeling genome folding, but the resolution—about 1 million base pairs—was too crude to allow scientists to really understand how genes interacted with specific regulatory elements. More detail was needed to understand how cells know which areas of the genome should be talking [to each other], and which shouldn’t,” said Dekker. After all, “you don’t want everybody talking to each other; you want [your genome] to have a decent conversation.”
Recent advances in deep sequencing are now providing researchers with a way to glean that detail.Dekker and his colleagues discovered, for example, that chromosomes can be divided into folding domains—megabase-long segments within which genes and regulatory elements associate more often with one another than with other chromosome sections. The DNA forms loops within the domains that bring a gene into close proximity with a specific regulatory element at a distant location along the chromosome. Another group, that of molecular biologist Bing Ren at the University of California, San Diego, published a similar finding in the same issue of Nature.
Between the two groups, the researchers identified these domains in mouse and human embryonic stem cells and human fibroblasts, suggesting that they are “a fundamental property of the genome,” Ren said. Additionally, both groups found that deleting boundary sections of domains threw gene regulation into disarray, causing previously silent genes to be transcribed and vice versa. These results demonstrate that “domain structure is essential to keep the gene program tightly regulated,” said Ren.
“I think the discovery of [folding] domains will be one of the most fundamental [genetics] discoveries of the last 10 years,” Dekker said. The big questions now are how these domains are formed, and what determines which elements are looped into proximity.
Read more here/Leia mais aqui: The Scientist

MicroRNA miR-941, um gene só nos fez humanos???

Evolution of the human-specific microRNA miR-941

Hai Yang Hu, Liu He, Kseniya Fominykh, Zheng Yan, Song Guo, Xiaoyu Zhang, Martin S. Taylor, Lin Tang, Jie Li, Jianmei Liu, Wen Wang, Haijing Yu & Philipp Khaitovich

AffiliationsContributionsCorresponding authors

Nature Communications 3, Article number: 1145 doi:10.1038/ncomms2146

Received 15 February 2012 Accepted 20 September 2012 Published 23 October 2012


MicroRNA-mediated gene regulation is important in many physiological processes. Here we explore the roles of a microRNA, miR-941, in human evolution. We find that miR-941 emerged de novo in the human lineage, between six and one million years ago, from an evolutionarily volatile tandem repeat sequence. Its copy-number remains polymorphic in humans and shows a trend for decreasing copy-number with migration out of Africa. Emergence of miR-941 was accompanied by accelerated loss of miR-941-binding sites, presumably to escape regulation. We further show that miR-941 is highly expressed in pluripotent cells, repressed upon differentiation and preferentially targets genes in hedgehog- and insulin-signalling pathways, thus suggesting roles in cellular differentiation. Human-specific effects of miR-941 regulation are detectable in the brain and affect genes involved in neurotransmitter signalling. Taken together, these results implicate miR-941 in human evolution, and provide an example of rapid regulatory evolution in the human linage.

Subject terms: Biological sciences Evolution Molecular biology


David M. Raup, um evolucionista honesto, 'falou e disse': os cientistas não sabem explicar as extinções das espécies

"A realidade perturbadora é que para nenhuma das milhares das extinções bem documentadas no passado geológico nós temos uma explicação sólida do por que ocorreu a extinção. Nós temos muitas propostas em casos específicos, é claro: … Eles são todos cenários plausíveis, mas não importa quão plausíveis, eles não podem ser demonstrados como verdadeiros além da dúvida razoável. Cenários alternativos igualmente plausíveis podem ser inventados com facilidade, e nenhum tem o poder preditivo no sentido de que pode mostrar a priori que uma dada espécie ou tipo anatômico foi destinado à extinção."

"The disturbing reality is that for none of the thousands of well-documented extinctions in the geologic past do we have a solid explanation of why the extinction occurred. We have many proposals in specific cases, of course: … These are all plausible scenarios, but no matter how plausible, they cannot be shown to be true beyond reasonable doubt. Equally plausible alternative scenarios can be invented with ease, and none has predictive power in the sense that it can show a priori that a given species or anatomical type was destined to go extinct." David M. Raup, Extinction: Bad Genes or Bad Luck? (New York: W. W. Norton, 1991, p. 17).

Darwin, são 550 mil visitantes deste blog!!!

sexta-feira, novembro 23, 2012

Source/Fonte: ClustrMaps

550 mil visitantes!!! Darwin, muito obrigado!!!

O córtex cerebral de Albert Einstein: uma descrição e análise preliminar de fotografias não publicadas

The cerebral cortex of Albert Einstein: a description and preliminary analysis of unpublished photographs

Dean Falk1,2, Frederick E. Lepore3,4 and Adrianne Noe5

Author Affiliations

1 Department of Anthropology, Florida State University, Tallahassee, FL 32306-7772, USA

2 School for Advanced Research, Santa Fe, NM 87505, USA

3 Department of Neurology, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA

4 Department of Ophthalmology, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA

5 National Museum of Health and Medicine, Silver Spring, MD 20910, USA

Correspondence to: Dean Falk, School for Advanced Research, 660 Garcia Street, Santa Fe, NM 87505, USA E-mail: dfalk@fsu.edu or falk@sarsf.org

Received June 12, 2012.

Revision received August 21, 2012.

Accepted August 17, 2012.


Upon his death in 1955, Albert Einstein’s brain was removed, fixed and photographed from multiple angles. It was then sectioned into 240 blocks, and histological slides were prepared. At the time, a roadmap was drawn that illustrates the location within the brain of each block and its associated slides. Here we describe the external gross neuroanatomy of Einstein’s entire cerebral cortex from 14 recently discovered photographs, most of which were taken from unconventional angles. Two of the photographs reveal sulcal patterns of the medial surfaces of the hemispheres, and another shows the neuroanatomy of the right (exposed) insula. Most of Einstein’s sulci are identified, and sulcal patterns in various parts of the brain are compared with those of 85 human brains that have been described in the literature. To the extent currently possible, unusual features of Einstein’s brain are tentatively interpreted in light of what is known about the evolution of higher cognitive processes in humans. As an aid to future investigators, these (and other) features are correlated with blocks on the roadmap (and therefore histological slides). Einstein’s brain has an extraordinary prefrontal cortex, which may have contributed to the neurological substrates for some of his remarkable cognitive abilities. The primary somatosensory and motor cortices near the regions that typically represent face and tongue are greatly expanded in the left hemisphere. Einstein’s parietal lobes are also unusual and may have provided some of the neurological underpinnings for his visuospatial and mathematical skills, as others have hypothesized. Einstein’s brain has typical frontal and occipital shape asymmetries (petalias) and grossly asymmetrical inferior and superior parietal lobules. Contrary to the literature, Einstein’s brain is not spherical, does not lack parietal opercula and has non-confluent Sylvian and inferior postcentral sulci.

Key words

Albert Einstein Broca’s area parietal lobules inferior third frontal gyrus prefrontal cortex



Brodmann area

© The Author(s) 2012. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Michael Behe entrevistado no Academia em Debate da Universidade Presbiteriana Mackenzie

Assista aqui no YouTube

O gêmeo do mágico: C. S. Lewis e o caso contra o cientificismo

quinta-feira, novembro 22, 2012


Contra Dobzhansky, Kirschner 'falou e disse': a evolução não é a base fundamental da biologia!!!

terça-feira, novembro 13, 2012

O mantra de Theodosius Dobzhansky reverbera na retórica evolucionista contra os críticos e oponentes da teoria da evolução de Darwin através da seleção natural e n mecanismos evolucionários de A a Z (eita teoria científica extremamente plástica): 

"Nada em biologia faz sentido a não ser à luz da evolução".

Mas há controvérsia, e da parte de biólogos evolucionistas de renome:

“Na verdade, nos últimos 100 anos, quase toda a biologia tem avançado independente da evolução, exceto a biologia evolucionária. A biologia molecular, a bioquímica, fisiologia, não levaram em conta a evolução de modo algum.” 

“In fact, over the last 100 years, almost all of biology has proceeded independent of evolution, except evolutionary biology itself. Molecular biology, biochemistry, physiology, have not taken evolution into account at all.” 

- Dr. Marc Kirschner, chefe do Departamento de Sistemas de Biologia, Faculdade de  Medicina da Universidade Harvard, em entrevista concedida ao Boston Globe, em 2005.


Traduzindo em miúdos: Nada em biologia faz sentido a não ser à luz das evidências, e aonde elas forem dar...

Um problema sério para os darwinistas: a epistasia diminui as chances das mutações benéficas

segunda-feira, novembro 12, 2012

Um problema sério para os darwinistas: a epistasia diminui as chances das mutações benéficas

Evolution News & Views November 8, 2012 5:52 AM | Permalink

Um artigo recente na Nature verifica que a epistasia (interações entre as mudanças genéticas) é muito mais disseminada do que previamente considerada. Isso limita muito a capacidade de mutações benéficas conferirem aptidão [boa condição física] aos organismos.

No neodarwinismo clássico, as mutações podem ser consideradas como alterações independentes de um gene local. As mutações podem ser neutras, deletérias, ou benéficas. Como Darwin a personificou – “A seleção natural está examinando minuciosamente diariamente e a cada hora, através do mundo, as variações mais insignificantes; rejeitando aquelas que são más, preservando e acrescentando todas as que são boas.” [Nota deste blogger: Darwin in Origem das Espécies, cap. 4 Seleção natural, 6ª. ed., 1872] Essa história da carochinha simplista se complicou com a epistasia.

Image not related to this article/Imagem não relacionada a este artigo.

A epistasia pode ser comparada a mudanças em um software em vez de um dicionário. No dicionário, a mudança de apenas uma letra pode não causar um efeito drástico na mensagem. No software, não obstante, as rotinas são frequentemente dependentes de outras rotinas. As rotinas do software têm inputs e outputs; elas formam redes de alianças. Mudar uma sub-rotina pode se esparramar através do software, causando múltiplos efeitos, mais provavelmente efeitos danosos. É por isso que os engenheiros de software rotineiramente executam testes em todo o sistema após fazer mudanças.

A epistasia é igual a isso; uma mutação em um gene pode causar danos em genes distantes. O neodarwinismo tem de ser modificado para incorporar os efeitos da epistasia. Tem que postular que os genes neutros são somente neutros no todo, e que as mutações benéficas são somente benéficas no todo. Mutações pontuais não podem mais ser consideradas isoladamente; o que é benéfico em um contexto pode ser deletério em outro.

Uma equipe de geneticistas na Espanha pesquisou o grau de epistasia em genomas publicados e descobriu que é muito mais disseminado que anteriormente considerado. No artigo “Epistasis as the primary factor inmolecular evolution” [Epistasia como o fator principal na evolução molecular] Breen et al. descobriram o seguinte:

... a taxa de substituição medida de aminoácido na evolução recente é 20 vezes menor do que a taxa de evolução neutra e uma ordem de magnitude muito menor do que esperada na ausência de epistasia. Esses dados indicam que a epistasia é difusiva por toda a evolução de proteína: cerca de 90% de todas as substituições de aminoácidos têm um impacto neutro ou benéfico somente nos backgrounds genéticos nas quais ocorrem, e devem, portanto, ser deletérias em um background diferente de outras espécies. Nossas descobertas mostram que a maioria das substituições de aminoácidos tem efeito de aptidão diferente em espécies diferentes e que a epistasia fornece o principal quadro conceitual para descrever o tempo e modo da evolução de proteína de longo termo. (Ênfase adicionada.)

[... the measured rate of amino-acid substitution in recent evolution is 20 times lower than the rate of neutral evolution and an order of magnitude lower than that expected in the absence of epistasis. These data indicate that epistasis is pervasive throughout protein evolution: about 90 per cent of all amino-acid substitutions have a neutral or beneficial impact only in the genetic backgrounds in which they occur, and must therefore be deleterious in a different background of other species. Our findings show that most amino-acid substitutions have different fitness effects in different species and that epistasis provides the primary conceptual framework to describe the tempo and mode of long-term protein evolution. (Emphasis added.)]

Seria difícil melhorar a explicação deles de como a epistasia afeta a evolução, mas eis aqui:

Uma substituição de aminoácido que for neutra ou benéfica em um contexto genético pode ser deletéria em outro. Tal situação, quando o efeito de aptidão de um estado de alelo depende do estado de alelo em outros loci, é chamada de epistasia. As teorias neutral e seletiva de evolução de proteína fornecem um quadro exato para o entendimento da evolução de proteína de longo termo somente se os estados de aminoácidos em contextos genéticos diferentes tenham o mesmo efeito sobre a aptidão, isto é, se a epistasia for rara. Na ausência de epistasia, quando os efeitos de aptidão de todos os estados de aminoácidos forem independentes um do outro, as substituições em espécies diferentes são esperadas ter efeitos semelhantes na aptidão exceto em casos onde essas substituições possibilitem as diferenças na adaptação em condições ambientais. Nesse caso, se o estado do aminoácido fosse descoberto em uma espécie em uma sequência de proteína que não esteja diretamente envolvida na adaptação ambiental, tal como a proteína de manutenção, então o mesmo estado de aminoácido deve ser aceitável em um sítio ortólogo em espécies diferentes. Contudo, se a epistasia for comum então as substituições de aminoácido que foram benéficas ou neutras em uma espécie devem ser frequentemente deletérias em outra. Portanto, desvendar a extensão e a base da epistasia pode ser crucial para a compreensão das diferenças nas sequências de proteínas entre as espécies e a evolução de proteína de longo termo. No presente, pesquisas das diferenças na aptidão das substituições em contextos genéticos diferentes consideram genes ou eventos específicos, e é desconhecida qual a fração de substituições de aminoácidos que ocorrem em uma espécie que seria também aceitável em outra espécie se elas tivessem que ocorrer em sítios ortólogos (mas vide a ref. 11). Aqui nós desenvolvemos uma abordagem para quantificar o impacto da epistasia em evolução de proteína e demonstramos que os efeitos de aptidão da maioria das substituições de aminoácidos deve depender no contexto genético onde elas ocorrem. (Referências deletadas.)

[An amino-acid substitution that is neutral or beneficial in one genetic context may be deleterious in another. Such a situation, when the fitness effect of one allele state depends on the allele states at other loci, is called epistasis. Both the neutral and selective theories of protein evolution provide an accurate framework for understanding long-term protein evolution only if amino-acid states in different genetic contexts have the same effect on fitness, that is, if epistasis is rare. In the absence of epistasis, when the fitness effects of all amino-acid states are independent of one another, substitutions in different species are expected to have similar effects on fitness except in cases where these substitutions enable differences in adaptation to environmental conditions. In that case, if an amino-acid state were found in one species in a protein sequence that is not directly involved in environmental adaptation, such as a housekeeping protein, then the same amino-acid state should be acceptable in an orthologous site in a different species. However, if epistasis is common then amino-acid substitutions that were beneficial or neutral in one species should often be deleterious in another. Therefore, unravelling the extent and basis of epistasis may be crucial to understanding differences in protein sequences between species and long-term protein evolution. At present, studies of the differences in the fitness of substitutions in different genetic contexts consider specific genes or events, and it is unknown what fraction of amino-acid substitutions that occur in one species would also be acceptable in another species if they were to occur in orthologous sites (but see ref. 11). Here we develop an approach to quantifying the impact of epistasis in protein evolution and show that the fitness effects of most amino-acid substitutions must depend on the genetic context in which they occur. (References deleted.)]

Eles descobriram que a epistasia não somente é muito mais predominante do que antes pensado, é o “principal quadro conceitual para descrever o tempo e o modo de evolução de proteína de longo termo”. Deve ser intuitivamente óbvio que alterar um gene acoplado a outros genes tornam o progresso neodarwinista muito mais improvável. Uma mutação benéfica tem de ser benéfica em mais contextos. Semelhantemente, as mutações neutras ou aproximadamente neutras serão menos frequente, pois existe uma maior probabilidade que terão efeitos deletérios em outros genes. Isso lança luz sobre o por que de os autores descobrirem que a “a seleção positiva não era comum na evolução das proteínas em nossa série de dados”, de acordo com um teste que eles usaram na sua busca.

Mesmo se uma mutação benefica sobreviver para melhorar a aptidão sobre uma espécie em um ambiente, não há garantia de que a mesma mutação irá melhorar outra espécie. “Assim, um aminoácido que foi benéfico a uma espécie por causa de uma adaptação ambiental específica pode ser detrimental a uma espécie que não vive no mesmo ambiente”, eles disseram. Os evolucionistas não podem evitar este problema, porque as “interações epistáticas são a norma e não a exceção quando nós consideramos as substituições de aminoácido nas sequências de proteínas.”

Com toda esta má notícia para o neodarwinismo, os autores poderiam resgatar o progresso evolucionário? Que pena, não. O ultimo parágrafo deles consistiu somente de questões difíceis levantadas por suas descobertas:

Nós identificamos a epistasia como um fator poderoso afetando a evolução da proteína a longo termo, e um fator que deve ser invocado para explicar por que a vasta maioria das substituições de aminoácidos que ocorrem em uma espécie não pode ocorrer em outra independentemente se a seleção positiva desempenhe ou não o papel dominante no curso de fixação das substituições de aminoácido em específicos contextos genéticos. Uma perspectiva epistática de evolução molecular leva à formulação de diversas questões fundamentais, além das perguntas em grande parte não respondidas propostas por John Maynard Smith em 1970 (ref. 12). Primeira, considerando-se um sítio específico, as substituições em quantos outros sítios no mesmo gene ou no genoma inteiro poderia mudar o poder da seleção associada com as substituições neste sítio? Segunda, de toda arede de interações epistática pares entre os sítios por todo o genoma, existem muitas sub-redes epistáticas que não se sobrepões ou a maioria dos sítios é interconectada dentro de toda a rede de interações epistáticas? Terceira, qual é a proporção de interações intergênicas a interações intragênicas epistáticas? Quarta, qual é a base molecular das interações epistáticas dentro do genoma? Finalmente, a predominante epistasia na evolução de proteína de longo termo levanta a possibilidade que interações epistáticas semelhantes deve ser predominante em evolução de curto termo e que as situações quando um polimorfismo é benigno ou benéfico a um indivíduo, mas é deletério para outro indivíduo dentro da mesma população pode ser mais comum do que atualmente pensado.

[We identify epistasis as a powerful factor affecting long-term protein evolution and one that must necessarily be invoked to explain why the vast majority of amino-acid substitutions that occur in one species cannot occur in another regardless of whether or not positive selection plays the dominant role in the course of fixation of amino-acid substitutions in specific genetic contexts. An epistatic perspective of molecular evolution leads to the formulation of several fundamental questions, in addition to the largely unanswered questions posed by John Maynard Smith in 1970 (ref. 12). First, given a specific site, substitutions in how many other sites in the same gene or in the entire genome could change the strength of selection associated with substitutions at this site? Second, out of the entire network of pairwise epistatic interactions between sites across the genome, are there many non-overlapping epistatic subnetworks or are most sites interconnected within the entire network of epistatic interactions? Third, what is the ratio of intergenic to intragenic epistatic interactions? Fourth, what is the molecular basis of epistatic interactions within the genome? Finally, pervasive epistasis in long-term protein evolution raises the possibility that similar epistatic interactions may be prevalent in short-term evolution and that situations when a polymorphism is benign or beneficial to one individual but deleterious to another individual within the same population may be more common than is thought at present.]

Isso é uma notícia potencialmente devastadora para os neodarwinistas. Desde que eles ainda estavam lutando em lidar com velhas questões não respondidas que John Maynard Smith levantou há 42 anos atrás, essas cinco questões novas ameaçam erodir a matéria prima da peneira de Darwin de seleção positiva de maneiras profundas e fundamentais.

Esta pesquisa vai ter uma influência imediata (nós podemos dizer “epistática”) sobre a teoria evolucionária? Provavelmente não. A ciência é como um grande navio que vira lentamente. Milhares de artigos científicos são publicados a cada semana. É duvidoso que muitos cientistas lerão ou repararão este artigo; aqueles que podem minimize-lo como um quebra-cabeça a ser resolvido mais tarde, vez que o neodarwinismo tem sido aceito há tempo como o paradigma aceito. Lembre-se que levou décadas (alguns dizem setenta anos) para que o artigo de Mendel fosse notado e considerado seriamente pelos teóricos evolucionistas; mesmo então, eles não abandonaram o paradigma – eles apenas incorporaram a herança mendeliana. A rede de crença darwinista é tão forte que os seus proponentes simplesmente virão com novos modelos a fim de incorporar a epistasia na rede. Esses geneticistas estavam levantando novos quebra-cabeças a serem resolvidos dentro do paradigma, eles não estavam procurando derrubá-lo.

É preciso alguém de for a para ler este artigo e ver o quão perturbador ele deve ser para a teoria neodarwinista consensual. Tudo que os céticos de Darwin podem fazer é continuar a apontar para artigos como esse como desafios severos à opinião consensual. Talvez alguns poucos escutem e considerem isso mais seriamente.

Mais provavelmente, se a visão de Thomas Kuhn da incomensurabilidade dos paradigmas estiver até parcialmente correta, os darwinistas e os céticos de Darwin vão se ignorar. Vai ser necessário uma nova geração de jovens cientistas de mentes abertas, ainda não apegados ao paradigma darwinista para liderarem a revolução científica há muito tempo esperada.



Apesar desta pesquisa trazer dificuldades imensas para a teoria da evolução de Darwin através da seleção natural e n mecanismos evolucionários [de A a Z] sou cético localizado quanto ao que este artigo possa causar realmente até mesmo nos darwinistas honestos e de mentes abertas. Razão? Como disse Theodosius Dobzhansky aos seus alunos de genética na USP que encontraram evidências contrárias em suas pesquisas com Drosophilas: “As evidências? Ora, que se danem as evidências, o que vale é a teoria!”

E ainda chamam isso de ciência. Eu chamo de desonestidade acadêmica, pois a ciência é a busca pela verdade, e os cientistas devem seguir as evidências aonde elas forem dar...


Longe de querer deixar biólogos e cientistas evolucionistas embaraçados com perguntas difíceis, o objetivo deste blogger é promover o avanço da ciência e demonstrar que o muito que é propalado como sendo fato, Fato, FATO da evolução pela Nomenklatura científica não é assim uma Brastemp no contexto de justificação teórica e que, apesar da retórica darwinista, o que é alegado como sendo conhecimento científico é, na verdade, assentimento a verdades aceitas a priori por força de um paradigma falido aceito mais por ideologia do que convencimento resultante das evidências encontradas no contexto de justificação teórica. Pobre ciência...

Genomas, proteomas e o dogma central...

sexta-feira, novembro 09, 2012


Genomes, Proteomes, and the Central Dogma

Sarah Franklin, PhD and Thomas M. Vondriska, PhD

- Author Affiliations

From the Departments of Anesthesiology (S.F., T.M.V.), Medicine (T.M.V.) and Physiology (T.M.V.), David Geffen School of Medicine, University of California, Los Angeles, CA.

Correspondence to Sarah Franklin or Thomas M. Vondriska, Departments of Anesthesiology, Medicine & Physiology, David Geffen School of Medicine, BH 557 CHS Bldg, 650 Charles Young Dr, Los Angeles, CA 90095. E-mail sfranklin@mednet.ucla.edu or tvondriska@mednet.ucla.edu

Key Words: genomics heart failure proteomics 


Arguably the greatest postmodern coup for reductionism in biology was the articulation of the central dogma. 1 Not since “humors” were discarded from medical practice and logic and experiment instituted as the cornerstones of physiology (which they remain today) had such a revolutionary idea transformed biology and enabled scientific inquiry. Because of its simplicity, the central dogma has the tantalizing allure of deduction: If one accepts the premises (that DNA encodes mRNA, and mRNA, protein), it seems one cannot deny the conclusions (that genes are the blueprint for life). As a result, the central dogma has guided research into causes of disease and phenotype, as well as constituted the basis for the tools used in the laboratory to interrogate these causes for the past half century.

The past decade, however, has witnessed a rapid accumulation of evidence that challenges the linear logic of the central dogma. Four previously unassailable beliefs about the genome—that it is static throughout the life of the organism; that it is invariant between cell type and individual 2–4; that changes occurring in somatic cells cannot be inherited (also known as Lamarckian evolution 5); and that necessary and sufficient information for cellular function is contained in the gene sequence—have all been called into question in the last few years. Revelations of similar scale have occurred in the transcriptome, with the discovery of the ubiquity (and variety) of mRNA splicing. 6 So too with the proteome, which has undergone perhaps the most dramatic shift in …

Estratificação evolucionária e os limites para a perfeição celular

Evolutionary layering and the limits to cellular perfection

Michael Lynch1

- Author Affiliations

Department of Biology, Indiana University, Bloomington, IN 47405

Contributed by Michael Lynch, September 24, 2012 (sent for review June 19, 2012)


Although observations from biochemistry and cell biology seemingly illustrate hundreds of examples of exquisite molecular adaptations, the fact that experimental manipulation can often result in improvements in cellular infrastructure raises the question as to what ultimately limits the level of molecular perfection achievable by natural selection. Here, it is argued that random genetic drift can impose a strong barrier to the advancement of molecular refinements by adaptive processes. Moreover, although substantial improvements in fitness may sometimes be accomplished via the emergence of novel cellular features that improve on previously established mechanisms, such advances are expected to often be transient, with overall fitness eventually returning to the level before incorporation of the genetic novelty. As a consequence of such changes, increased molecular/cellular complexity can arise by Darwinian processes, while yielding no long-term increase in adaptation and imposing increased energetic and mutational costs.

genetic load cellular evolution robustness nonadaptive evolution


↵1E-mail: milynch@indiana.edu.

Author contributions: M.L. designed research, performed research, analyzed data, and wrote the paper.

The author declares no conflict of interest.

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"Random genetic drift can impose a strong barrier to the advancement of molecular refinements by adaptive processes." 

[A deriva genética aleatória pode impor uma forte barreira ao avanço dos refinamentos moleculares através de processos adaptativos]

"Moreover, although substantial improvements in fitness may sometimes be accomplished via the emergence of novel cellular features that improve on previously established mechanisms" 

[Além disso, embora melhoras substanciais em aptidão possam algumas vezes ser realizadas via emergência de novas características celulares que melhoram a partir de mecanismos previamente estabelecidos]

"Increased molecular/cellular complexity can arise by Darwinian processes, while yielding no long-term increase in adaptation and imposing increased energetic and mutational costs. "

[Complexidade molecular/celular crescente pode surgir por processos darwinistas embora não produzindo aumento de longo termo na adaptação e impondo crescentes custos energéticos e mutacionais]


A deriva genética é principalmente um movimento 'degenerativo', e não generativo. As 'melhoras substanciais' mencionadas acima, basicamente equivalem ao 'Natural Genetic Engineering' [Engenharia genética natural] de James A. Shapiro, do Departamento de Bioquímica e Biologia Molecular, da Universidade de Chicago.

Finalmente, como temos aqui e ali mencionado neste blog, os processos darwinistas podem até aumentar a 'complexidade' (que é mais ou menos uma ação 'degenerativa', e não generativa), não é comparável à crescente 'complexidade funcional' conforme proposta pelos teóricos do Design Inteligente. Aqui Darwin é reprovado impiedosamente!!! Nem de segunda época ou dependência fica!!!

Muito obrigado Dr. Lynch, por ajudar a colocar mais um prego no caixão epistêmico de Darwin!!!

Revisitando um antigo mistério não resolvido: o que determina os níveis de diversidade genética dentro das espécies

quinta-feira, novembro 08, 2012

Revisiting an Old Riddle: What Determines Genetic Diversity Levels within Species?

Ellen M. Leffler1*, Kevin Bullaughey2#, Daniel R. Matute1#, Wynn K. Meyer1#, Laure Ségurel1,3#, Aarti Venkat1#, Peter Andolfatto4, Molly Przeworski1,2,3*

1 Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America, 2 Department of Ecology and Evolution, University of Chicago, Chicago, Illinois, United States of America, 3 Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois, United States of America, 4 Department of Ecology and Evolutionary Biology and the Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America


Understanding why some species have more genetic diversity than others is central to the study of ecology and evolution, and carries potentially important implications for conservation biology. Yet not only does this question remain unresolved, it has largely fallen into disregard. With the rapid decrease in sequencing costs, we argue that it is time to revive it.

Citation: Leffler EM, Bullaughey K, Matute DR, Meyer WK, Ségurel L, et al. (2012) Revisiting an Old Riddle: What Determines Genetic Diversity Levels within Species? PLoS Biol 10(9): e1001388. doi:10.1371/journal.pbio.1001388

Published: September 11, 2012

Copyright: © Leffler et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: E.M.L. was partially supported by National Institutes of Health Grant T32 GM007197. M.P. is a Howard Hughes Early Career Scientist. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

* E-mail: emleffler@uchicago.edu (EML); mfp@uchicago.edu (MP)

# These authors contributed equally to this work.

What evolutionary forces maintain genetic diversity in natural populations? How do diversity levels relate to census population sizes (Box 1)? Do low levels of diversity limit adaptation to novel selective pressures? Efforts to address such questions spurred the rise of modern population genetics and contributed to the development of the neutral theory of molecular evolution—the null hypothesis for much of evolutionary genetics and comparative genomics [1]–[3]. Yet these questions remain wide open and, for close to two decades, have been neglected [4]. Most notably, little progress has been made to resolve a riddle first pointed out 40 years ago on the basis of allozyme data: the mysteriously narrow range of genetic diversity levels seen across taxa that vary markedly in their census population sizes [5]. This gap in our understanding is glaring, and may hamper efforts at conservation (e.g., [6]).


Biologia do desenvolvimento enriquece a paleontologia

quarta-feira, novembro 07, 2012

Journal of Vertebrate PaleontologyVolume 32, Issue 6, 2012

Developmental biology enriches paleontology


J. G. M. Thewissen a, Lisa Noelle Cooper a &; Richard R. Behringer b 

pages 1223-1234

Received: 21 Oct 2011

Accepted: 19 Jun 2012

Version of record first published: 31 Oct 2012


Paleontology provides information about the history of morphological transformations, whereas developmental biology provides information about how such transformations happen at a mechanistic level. As such, developmental evidence enriches paleontology in formulating and assessing hypotheses of homology, character definition, and character independence, as well as providing insights into patterns of heterochrony, evolvability of features, and explanations for differential rates of evolution. The focus of this article is to review a series of case studies that illustrate how our understanding of paleontology is enriched by data generated by developmental biologists. The integration of paleontological and developmental data leads to a greater understanding of evolution than either of these sciences could have reached alone. Our case studies range from fish to mammals and involve somite and vertebral formation, limb loss, hand and foot patterning, and tooth formation.


O projeto ENCODE revelou que o DNA lixo não era lixo, mas há quem pense o contrário: é LIXO!!!

terça-feira, novembro 06, 2012

Copyright © 2012 Elsevier Ltd All rights reserved.

Current Biology, Volume 22, Issue 21, R898-R899, 6 November 2012


The C-value paradox, junk DNA and ENCODE

Sean R. Eddy 

HHMI Janelia Farm Research Campus, Ashburn VA 20147, USA

What is the C-value paradox? You might expect more complex organisms to have progressively larger genomes, but eukaryotic genome size fails to correlate well with apparent complexity, and instead varies wildly over more than a 100,000-fold range. Single-celled amoebae have some of the largest genomes, up to 100-fold larger than the human genome. This variation suggested that genomes can contain a substantial fraction of DNA other than for genes and their regulatory sequences. C.A. Thomas Jr dubbed it the ‘C-value paradox’ in 1971.

The C-value paradox is related to another puzzling observation, called ‘mutational load’: the human genome seems too large, given the observed human mutation rate. If the entire human genome were functional (in the sense of being under selective pressure), we would have too many deleterious mutations per generation. By 1970, rough calculations had suggested to several authors that maybe only 1–20% of the human genome could be genic, with the rest evolving neutrally or nearly so.

So why not call it the ‘genome size paradox’? What is a ‘C-value’ anyway? ‘C-value’ means the ‘constant’ (or ‘characteristic’) value of haploid DNA content per nucleus, typically measured in picograms (1 picogram is roughly 1 gigabase). Around 1950, the observation that different cell types in the same organism generally have the same C-value was part of the evidence supporting the idea that DNA was responsible for heredity.

Why is it a paradox, maybe we just don’t understand how to measure complexity? For sure, we don’t understand how to meaningfully measure an organism’s complexity, and we don’t have any theoretical basis for predicting how many genes or regulatory regions one needs. But the C-value paradox isn’t just an observation that different species have different genome sizes, it’s the observation that even similar species can have quite different genome sizes. For example, there are many examples of related species in the same genus that have haploid genome sizes that differ by three- to eight-fold; this is particularly common in plants, as seen in species of rice (Oryza), Sorghum, or onions (Allium). The maize (Zea mays) genome expanded by about 50% in just 140,000 years since its divergence from Zea luxurians (and not merely by polyploidization). Unlike what we expect of genes and regulatory sequences, which generally evolve slowly and conservatively, for some reason genome size can change rapidly on evolutionary timescales.

OK, cool; I’ve already come up with some hypotheses — maybe the extra DNA has a structural role in the nucleus? Remember, the C-value paradox is old. Many hypotheses have been proposed and carefully weighed in the literature. At first, people looked for explanations in terms of some functional significance of the extra DNA — an adaptive function that would maintain nongenic, nonregulatory DNA by natural selection. But to explain mutational load — and more modern observations from comparative genomics, showing that only a small fraction of most eukaryotic genome sequence is conserved and under selective pressure — you have to posit an adaptive role where only the bulk amount of the DNA matters, not its specific sequence. To explain the C-value paradox, you have to explain why this bulk amount would vary quite a bit even between similar species. Although some such adaptive explanations have been speculated, a rather different line of thinking, starting with Ohno and others in the early 1970s, ultimately led to a reasonably well-accepted explanation of the C-value paradox.

So what is the explanation for the C-value paradox? Genomes carry some fraction of DNA that has little or no adaptive advantage for the organism at all. Some genomes carry more than others, and some genomes carry quite a lot of it. Ohno, who believed that strongly polarizing statements clarify scientific debate, called this ‘junk DNA’.

So the idea is that all noncoding DNA is junk DNA? No. Of course we’ve also known since the earliest days of molecular biology (including the Jacob/Monod lac operon paradigm) that genes are regulated by sequences that often occur in noncoding DNA. Rather the idea is that there is a fraction of DNA that is useful and functional for the organism (genes and regulatory regions) which does more or less scale with organismal complexity, and a ‘junk’ fraction which varies widely in amount, creating the C-value paradox.

I’m having a hard time with your derogatory term ‘junk’… Ohno’s zest for polarizing provocation went too far. Far from clarifying, his term tends to incense people, and the science behind the idea gets muddled. If you like, call it ‘nonfunctional’ DNA instead — and by nonfunctional, we mean ‘having little or no selective advantage for the organism’. These words, especially ‘for the organism’, will become important.

How much nonfunctional DNA an organism would harbor will be a tradeoff between how deleterious it is to carry versus how easy it is to get rid of. It’s actually not obvious that extra DNA would be all that deleterious; DNA replication is a relatively small part of the energy budget of most organisms. Still, DNA deletions are common enough mutations. If there were even a small selective disadvantage to having a junky genome, especially in species with large population sizes (where small selection coefficients have more effect) and fast growth rates (where an obese genome might especially be a hindrance), it would be surprising to see a lot of nonfunctional DNA.

That’s what I mean: natural selection wouldn’t tolerate junk; if you can’t explain how this extra DNA got there and why it’s maintained, ‘junk DNA’ is an argument from ignorance — you can’t just assume it’s junk. Ohno was mostly focused on pseudogenes, which do occur, but not nearly in large enough numbers to explain the C-value paradox. So indeed, what Ohno’s idea lacked to make it convincing was an observable mechanism that creates large amounts of junk DNA rapidly, faster than natural selection deletes it. In 1980, two landmark papers, by Orgel and Crick and by Doolittle and Sapienza, established a strong case for such a mechanism. They proposed that ‘selfish DNA’ elements, such as transposons, essentially act as molecular parasites, replicating and increasing their numbers at the (usually slight) expense of a host genome. Selfish DNA elements function for themselves, rather than having an adaptive function for their host.

The massive prevalence of transposable elements in eukaryotic genomes was only just becoming appreciated at the time. One transposable element in humans, called Alu, occurs in about a million copies and accounts for about 10% of our genome. Almost all copies of transposons in genomes are partial or defective elements that were inserted in the evolutionary past and are now decaying away, largely by neutral mutational drift. Active DNA transposons (one kind of ‘selfish DNA’) generate a mass of decaying dead transposons (one source of ‘junk DNA’).

We can affirmatively identify transposon relics by computational genome sequence analysis methods. These studies show that transposable elements invade in waves over evolutionary time, sweeping into a genome in large numbers, then dying and decaying away. 45% of the human genome is detectably derived from transposable elements. The true fraction of transposon-derived DNA in our genome must be greater, because neutrally evolving sequences decay so rapidly that after only a hundred million years or so, they eventually become too degraded to recognize. The C-value paradox is mostly (though not entirely) explained by different loads of decaying husks of transposable elements. Larger genomes have a larger fraction of transposon relics.