Posts Tagged ‘EvoDevo’

EvoDevo IGERT Symposium, Day 1

November 14, 2009

[I'm at Indiana University, attending the 2009 IGERT symposium on evolution, development, and genomics.]

Tonight, we heard from Patrick Phillips and PZ Myers.

Patrick gave a broad overview of the past, present, and future of EvoDevo.  The central question of EvoDevo is: how do developmental systems evolve?  Conversely, we can ask: how does development shape the evolutionary process?  Although EvoDevo has witnessed big progress in the last decade, these central questions are unanswered.  Patrick consequently said, “[grad students], your future is secure!”

Patrick claims that EvoDevo lacks a central theory.  In other fields, there is a unit of study: chemistry examines atoms, biochemistry examines molecules, molecular biology examines DNA, population genetics examines DNA sequences, population biology examines individuals, and community ecology examines species.  For EvoDevo, Patrick asserts the unit of study should be (and is) the cell.

Finally, Patrick talked about experimental barriers for EvoDevo.  The most significant barrier is that the genotype-phenotype map is still not completely understood.  A large proportion of research is focused on simply finding genes, let alone understanding how they affect phenotype.  Patrick used Hopi Hoekstra’s work as an example of successful geneotype-phenotype mapping.  (Hopi’s lab revealed the genetic mechanisms controlling mouse coloration patterns).  Although Hopi’s work is seminal, but we still have a long ways to go towards understanding the genetic mechanisms that control complex phenotypes, such as behavior.

After Patrick’s introduction, PZ Myers gave a talk titled, “Repelled and Fascinated: Coping with the Public Response to Evolution.”  PZ Myers authors a famous (or infamous) blog about evolutionary biology, and has lately become a lightening rod for attacks from the creationist and intelligent design community.

PZ started by showing results from pew polls, suggesting that about 50% of the U.S. public does not believe in evolution.  Furthermore, about 16% of U.S. high school science teachers don’t believe in evolution [citation: Berkman et al, 2008, PLoS Bio].  Although these numbers are alarming, PZ thinks the public is only nominally creationist and confounded by the loud voices of creationists.

PZ next gave a “pocket guide to creationism” in which he explained the history of the creationist movement.  PZ traces creationism’s roots to Archbishop James Ussher, who calculated the age of the earth using dates from the bible.  Until the early 1900’s, most of U.S. public was willing to accept the bible as metaphor.  The *best* slide from PZ’s talk was a phylogeny expressing the history of creationism.  I include it here, but I’m sorry that it’s slightly blurry:

[Note to PZ: if you'd rather I don't share this photo, let me know]

PZ went on to discuss some significant events in the history of creationism: the Scopes trail in 1925, The Genesis Flood in 1961, Edwards vs. Aguillard in 1987, and Kitzmiller vs. Dover in 2005.  PZ claims that “scientific” creationism comes from Seventh Day Adventism, but is has been intellectually laundered to hide or sever it’s Seventh Day Adventist roots.  The most radical change in the creationist movement has been towards portraying evolutionary biologists as “evil.”

In response to the increasing fundamentalism of the creationist movement, PZ asserts that we (evolutionary biologists) should be more active with our outreach.  In particular, we should write blogs!

Journal Club: Structural and Functional Constraints in the Evolution of Protein Families

October 14, 2009

The theme of this year’s IGERT EvoDevo symposium is “Current Frontiers of Evolution, Development, and Genomics.”  Every Friday, starting this week and ending December 4th, our IGERT group is hosting a journal club discussion about our own research in the broader context of paradigm-shifting publications in Evo/Devo/Geno.  This week, I’m leading the discussion about my research in computational methods for ancestral sequence reconstruction in the context of a recent review by Catherine Worth, Sungsam Gong, and Tom L. Blundell titled “Structural and Functional Constraints in the Evolution of Protein Families.” If your campus provides access to the journal Nature Reviews, the paper can be found here: http://www.nature.com/nrm/journal/v10/n10/abs/nrm2762.html

Here are my insights into why this paper is fundamentally relevant for anyone working with genetic sequence data in an evolutionary context. . .

Scientific frontiers appear when we integrate analyses from the micro and the macro scale. Examples of this include how biology is informed by chemistry, chemistry is informed by physics, and classical physics is informed by quantum physics.  This trend is true for EvoDevo: we are rapidly arriving at an understanding of evolution from increasingly scientific first principles.  To be specific, we are beginning to understand how mutations in protein sequence and structure — at the biophysical scale — have consequences for the function and phenotype of cells, species, and individuals — at the macro scale [see Dean and Thornton, Nature Reviews 2007].

In order to reveal the evolutionary trajectory of a particular protein structure, we need to examine ancient forms of that protein.  However, the simple acquisition of ancestral molecules can be a major obstacle when we examine evolutionary histories over millions of years because the ancestral forms are typically extinct.  As a computational alternative, we can time travel via statistical inference [see Thornton, Nature Reviews 2004].

I study computational and phylogenetic methods that make it possible for us to probabilistically infer phylogenies and reconstruct ancestral gene sequences.  One of the most important inventions in the history of phylogenetic methods is the use of Markov models to approximate the evolution of gene sequences.  Markov models are used all over the place in information science: to model natural language, radio transmissions, and white noise.  Markov models are used in speech recognition, your email’s spam filter, and global weather prediction.  Google’s core search algorithm is fundamentally just a complex Markov model.

The core idea of the Markov Model concerns characters transitioning (i.e. mutating) over time.  Suppose we have some character — like a single nucleotide or an amino acid — and it currently is in state X, where X is one of the letters in our nucleotide or amino acid alphabet.  Over time of length t, X will mutate to state Y with probability determined by a matrix of relative substitution ratios.  This model follows the Markov property, where the probability of Y later mutating to state Z over time t2 is independent of its prior state X.

If we calculate transition probabilities for all branches in a phylogenetic tree, we can thus calculate the likelihood of that tree and infer the maximum a posteriori ancestral protein sequence.  In this discussion, I will avoid articulating all the mathematical minutiae of how we calculate probabilities for trees and ancestral sequences; you can learn more by reading this excellent book edited by Oliver Gascuel.  Instead, I want to focus on the substitution matrix: it is an approximation of molecular evolution and it makes critical assumptions about evolutionary forces.

In it’s simplest form (as a 4×4 nucleotide matrix or 20×20 amino acid matrix) substitution matrices assume that all residues with the same state are in a homogenous biophysical environment, and are thus exposed to the same mutational forces.  For example, the WAG matrix assumes that all glutamic acids (E) can be treated equally, and thus the relative substitution rate for any glutamic acid mutating into asparagine (D) is 6.174, while the relative rate of any glutamic acid mutating to cystine (C) is 0.021.  The assumption of structural homogeneity is often invalid; for example, as is illustrated in this week’s review by Worth et al., residues buried in solvent-inaccessible cores of a protein tend to be more conserved than residues located on the exterior of proteins.  This insight implies that we need a secondary substitution matrix expressing relative mutation rates for residues located in protein cores.  As an example, if E stands for an external glutamic acid and E’ stands for a core glutamic acid, we should expect the relative substitution rate for E-to-D to be larger than the relative rate for E’-to-D’.

The article by Worth et al. reviews a large historical body of results concerning protein structure conservation.  The article further describes how we can use environment-specific substitution tables (ESSTs) to explicitly capture information about structural conservation into our Markov model of evolution.  The insights from this paper are fundamental for anyone working with genetic sequence data in an evolutionary context.

Worth CL, Gong S, & Blundell TL (2009). Structural and functional constraints in the evolution of protein families. Nature reviews. Molecular cell biology, 10 (10), 709-20 PMID: 19756040

Sean Carroll, EvoDevo @ U.O.

May 5, 2009

Sean Carroll visited the University of Oregon over the past couple days.  He’s authored hundreds of research papers and several books on the subject of evolutionary biology.  Here is a brief summary of Sean’s visit. . .

Last night, Sean gave the fifth lecture in our Darwin series.  This was a public talk (for scientists and non-scientists alike) and Sean presented material from his latest book “Remarkable Creatures.” Specifically, he focused on the harrowing stories of Wallace, Darwin, and Bates sailing around South America and the Galapagos islands.  The greatest insight from this lecture was that Wallace and Darwin independently converged on the theory of natural selection.  I think their convergence testifies to the strength of the theory.

Today, Sean gave a technical talk (for the EvoDevo crowd) titled “Endless Flies Most Beautiful: Cis-Regulatory Sequences and the Evolution of Animal Form.”  Sean focused on the central EvoDevo question: How do forms (i.e. morphologies) evolve? He thinks an examination of mosaic pleiotropy is the key to answering this question.   Historically, gene duplication was thought to be the primary mechanism by which new forms evolved.  Sean cites Susumu Ohno’s classic book “Evolution by Gene Development.” However, Sean countered Ohno’s thesis by showing evidence that evolution might actually select against gene duplication.  As an example, the evolutionary history of anthropod and tetrapod Hox genes — a gene that is known to drive some morphologies —  is a story of gene loss, not gene duplication.

Later approaches to the EvoDevo question examined the role of protein sequence evolution, and then eventually King and Wilson examined the role of protein sequence expression.  Essentially, King and Wilson reduced the question “how do forms evolve?” to the micro-question of “how do cis-regulatory elements evolve?”  For the remainder of Sean’s talk, he focused on “cis-regulatory elements as the units of evolution.”

Before the EvoDevo community was examining regulatory elements, inter-species genetic analysis was typically occuring over large taxonomic distances.  This approach proved problematic because transcription factor binding sites are rarely conserved over large phylogenetic distances.  Consequently, the EvoDevo community was forced to find new systems for study.  Sean Carroll’s lab — for example — shifted focus away from studying butterflies and began investigating pigmentation diversity in Drosophila (see Nature, Trends in Genetics, and PNAS).  Unlike butterflies, Drosophila studies offered the ability to explore evolutionary mechanisms at a deeper mechanistic/genetic level.  Among many subsequent results, Sean’s lab discovered the Tan gene locus is responsible for  mosaic pleiotropy in Drosophila Santomea’s wing pigmentation.

Based on results from the Tan gene — and several other studies — Sean concluded that regulatory sequence evolution is the more likely mechanism of morphological change than the coding sequence itself (see PLoS Biology 2005).  Sean gave several examples to support this theory, including a story about the Engrailed gene: an ancient regulatory protein that was recently co-opted to control development of Drosophila wing spots.

Overall, this was an enlightening visit and I feel fortunate to be studying at a university that can engage this caliber science.  For more information, check-out The Carroll Lab.


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