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Darwin In the Genome: Molecular Strategies in Biological Evolution

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Even the most convinced evolutionist must struggle with comprehending how life in all its diversity could have arisen from a simple process of random mutation and selection. For perhaps the last 30 years, it has become apparent that DNA can be altered by a variety of processes that can vary it in ways that permit changes of a much more dramatic sort that should permit much more rapid and "effective" evolution. Several years ago, the author of this exceptionally interesting new book organized a conference under the auspices of the New York Academy of Sciences that brought together a wide diversity of scientists concerned with the molecular basis of evolutionary change. Using this meeting as a starting point and combining these discussions with her own original contributions to the field, Dr. Caporale has produced what seems to me to be the first comprehensive albeit preliminary view of how we came to be what we are. Through a series of descriptions of DNA alterations such as "slipping, jumping, repair and modular rearrangement", she convincing argues that the key to understanding evolution is the recognition that the evolutionary process itself is subject to variation, selection and evolution. Like any convincing arguement, after listening to her graceful discussion of example after example from the generation of antibody diversity and pathogen surface changes to the origin of cancer, her hypothesis begins to seem obvious. If you have ever struggled with understanding how evolutionary process could have produced something as complex as a human being, this is the book for you. It is written in a very direct, accessible style and should appeal to anyone from an interested lay person to a scientist (such as myself) who is not an expert in the area. I have a few minor concerns that should not detract in any serious way from the power and impact of this wonderful book. I felt the author over used analogies throughout the work. I often found the analogies more difficult to understand than the actual direct description of the phenomenon being described. I would also like to have seen more simple diagrams illustrating the types of changes in the DNA that were discussed. I also think that most scientists would strongly disagree with the statement that the sequencing of the human genome is/was the "greatest achievement in human intellectual history". While few would disagree that this is a major technical accomplishment, it in of itself pales before quantum mechanics, special and general relativity, recognition of the structure of DNA, etc. Finally, the weakest part of her argument is the reliance upon deleterious changes in DNA to build much of her case. She clearly recognizes this but argues that it is just more difficult to see similar molecular alterations that have had positive evolutionary effects. I tend to think she is probably correct, but only more detailed studies of a variety of genomes will unambiguously reveal this. I was a bit disappointed that she failed to discuss the "entropic DNA hypothesis" since this at least partially resolves some of the uncertainties in her arguments but this is perhaps not unexpected on my part since I am the author of said idea. In summary, this is an exceptional book by any criteria. I hope it is widely read and discussed and the author gives us a second edition in 5-10 years that will keep us updated on a subject of central importance to all of us. If nothing else, read the last chapter and epilogue. The authors views on the philosophical, social and political implications of our new understanding of genomic structure and dynamics seem to me to be both beautiful and profound. The unity of life on earth has never been more eloquently described and elaborated than in this work. The more widely read this book is, the better it will be for all of us, especially in these difficult times.

I am not a trained biologist, but I enjoy reading in this area, and I enjoyed this book a good deal.

Basically, her thesis (which appears most clearly on page 130) is that genetic mutations are not random and are to some degree controlled by a meta-program of the DNA regulators that is subject to selection pressures. She posits an evolutionary theory, but spends most of her time gently explaining the actualities and details. She shows that her theory happens in the immune system and then makes reasonable suppositions that it probably happens on a broader scale. There are a lot of perhaps's and probably's in the book. She acknowledges that parts of her theory are controversial.

She is much clearer and less freighted with philosophical rhetoric than Lenny Moss's "What genes can't do," and she describes the complex genetic interaction with other cellular structures and exterior signals with almost as much subtlety. I liked her description of bacteria using quorum-sensors to decide whether to break apart as plasmids or whether to hunker down in a spore. She also seems to have an eye on the issues raised by IDist Michael Behe and makes a point of discussing the immune system and blood clotting as very much reducible and evolved mechanisms, though she doesn't attack creationism directly.

I give the book a four star because her prose is not as inspired as that of Stephen Jay Gould or Steven Pinker, and her metaphors don't always fly. Her grand gesture at the end did not leave me overwhelmed. There is still a lot of technical vocabulary, so not quite a light read, but much lighter than many. It will allow even smart high schoolers to learn the latest theories on that Mother of All Rube Goldberg Machines: Life.

Imagine you're sitting in the audience at a play, one with a large cast and a complex plot, Les Miserables, say, or Nicholas Nickleby. Only this play isn't presented in the usual way. Sometimes you see the actors but you can't hear them speak. Other times the curtain hides the stage, but you can hear the actors clearly. And sometimes you can both see the actors and hear them deliver their lines. After sitting through this odd drama, you're required to provide a detailed critique of the play to someone who hasn't seen it.

Some of what happened you'd know for certain, some of it you'd try to infer by piecing together partial information, and some of your explanation would be sheer guesswork. This seems to approximate current scientific writing about the human genome: some knowledge, some inference, some guesswork. We've learned a considerable amount about the overall structure of our genome during the past two decades. But there's a lot about the mechanics of how genes duplicate, edit and regulate themselves that remains hidden from us. Molecular biologist Lynn Helena Caporale uses her considerable knowledge of genomic functioning to update us on the current state of play and to buttress some speculative thinking about how genomes mutate. Her conclusions are controversial among evolutionary theorists, but they do provide a possible answer to a particularly bedeviling question: given the trillions of potential pathways and cul de sacs down which random mutation could have taken our genes, how did homo sapiens actually evolve to this level of functioning in the relatively short time we've been on the planet?

Dr. Caporale's thesis is that mutation might not be completely random. Instead, she speculates that genes may have evolved strategies for allowing high levels of variation in targeted areas for targeted purposes - fighting off bacterial infections, for example - in ways that don't disturb the essential functioning of the organism. As she states in the prologue, "a genome evolves a `worldview' of which types of changes, under what types of circumstances, may yield a new function and are less likely to destroy something essential."

Such genomes would have an evolutionary advantage because they could generate diverse offspring or adapt to new circumstances without having to rebuild what already works from scratch. She also demonstrates that our DNA can cut and paste blocks of genetic information, which means that we can take successful subroutines and recombine them to create new functions, similar to the way object oriented programming works in computer software. (We may have acquired some useful code from interactions with our good friends, bacteria, or our close cousins, the mouse and the fruit fly.) If genes work this way, then our evolution may have been more strategic and targeted than purely random mutation would account for, and natural selection would naturally favor the genomes with the most workable strategy for surviving and successfully replicating themselves.

Among the many fascinating glimpses into our functioning that this book provides are the strategies our cells employ to recognize, capture and neutralize viruses. There's an epic conflict going on in your gut at this very moment that makes the climactic battle scenes in Lord of the Rings look tepid and unimaginative. It's also fascinating to realize that our genes enact on the cellular level one of our most profound human dilemmas: how do you decide what should remain stable and what should change in order to secure the best future for yourself? Is the human dilemma just the basic genomic dilemma writ large? As the Irish poet William Butler Yeats put it so memorably, how can you tell the dancer from the dance?

There's a lot of detail in this book, and the non-biologist may struggle to absorb the nomenclature of molecular biology, and to track the splits, slips, swaps, loops, cuts, conversions, transmissions and transpositions that the 3 billion letters of your genome engage in. Dr. Caporale employs some elegant metaphors to make the play more intelligible. The reward for paying close attention is a awe-inspiring glimpse into what we are, along with some well-reasoned ideas about why we turned out this particular way.

Darwin in the Genome is a good Christmas choice for any budding but hesitant scientist on your list. Written by UC Berkeley molecular biologist Lynn Helena Caporale, the book explores the recent mapping of the human genome while adding the overlay of evolution on top of these exciting discoveries.

In the acknowledgements and a forward, Caporale writes about her own discovery that her future lay in the sciences and credits a savvy high school teacher with getting her hooked. After school homework support from her grandparents did not hurt either.
I particularly liked the chapters, "Mixing Up Genes for the CHildren," and "Family Heirlooms: A Framework for Evolution," as they gave me a new way to look at the hereditary traits of those closest to me and to think about the fragility of the individual genome and the need to guard it from invasive bacteria, ultraviolet light, radiation or other environmental triggers that might cause mutations and/or change its inherent integrity.

In fact, throughout the book, Caporale argues for scientific humility and urges would-be cloners to approach the genome with a sense of the sacred.
THere are also two fascinating chapters on Strategies as Targets , which explores the role of pathogens and "Strategies as Targets, Round Two: Cancer" which discusses why it is so difficult to cure cancer without killing the patient.

One reason this book is good for any curious soul, as well as for scientists, is its accessible and often poetic language. Each chapter is preceeded by a quote from a known international scholar, author or philosopher or playwrite. These epigraphs, like the one from Rachel Carson: "When opportunity arises, Life shall be waiting,"
or another by Primo Levi : "We are here for this....to make mistakes and to correct ourselves.. nature is..not impermeable to the intelligence; we must.. look for the opening or make it,"
frame the discussion and are also just plain inspiring in themselves.

I think high school and college readers will also appreciate the glossary in back.
Bravo to Ms. Caporale for giving us something we can bite our teeth into and not despair that the meal is too tough to chew and digest.

Back in 1996 Stuart Kauffman, in "At Home in the Universe: the Search for Laws of Self-Organization and Complexity", postulated convincingly on theoretical grounds that evolution would favor organisms which were good at evolution, i.e. they were more likely to generate favorable changes in their genome. Sex is theorized by many to have arisen as a means of responding to the evolution of disease causing agents, as well as to promote evolutionary adaptation in general. I myself, as I am sure many others, always questioned that organisms would have all this junk DNA, costly (in terms of energy) to maintain, without any use. Caporale's book attempts to gather all the evidence currently available that Kauffman was correct, and finds that junk DNA plays a role in facilitating evolution. Caporale also does a lot of speculating, because the body of experimental evidence is still in its infancy. Incidentally, Caporale gives the impression that the postulate I have ascribed to Kauffman (and which undoubtedly had earlier antecedents), is a new idea.

At times Caporale's book is almost painfully detailed in describing biological processes, albeit always without invoking organic chemistry. Her motivation is good: having gone through some concrete detail, for example about "slippery" DNA, the reader should be better able to appreciate the more general arguments. Caporale loves sustained metaphors; often the metaphors help, sometimes they get in the way. In general, I found the book uneven. The critical chapter on jumping genes left me with too many questions that I attribute to the writing. The final chapter, instead of being a much needed summary, presents material that anyone sophisticated enough to get that far, already knows. On the other hand, the chapter on the immune response was clearer than other accounts I have read, and the general topic of processes favoring successful evolution is fascinating. So my advice is: if you are already conversant with evolution, and willing to deal with some challenging material, perhaps sometimes unnecessarily challenging, read this book. In case you do not, I must point out that I was delighted to learn that there is now evidence that the intron RNA is not immediately destroyed after protein synthesis, and likely has some function to perform.

Darwin postulated that evolution resulted from the accumulation of small variations from generation to generation. Once Watson and Crick described the structure of DNA, many people thought that variation arose mostly from point mutations: changes, insertions, and deletions of single "letters" of the DNA code. Since then, it has become obvious that larger changes are more important. For example, whole segments of DNA, including genes and gene families, are duplicated; the copies are then available to be modified for new purposes while the originals still do their old jobs. A number of other books look at how such large changes promote evolution; this book focuses on molecular mechanisms behind these changes, i.e. where the variation comes from.

For example, there are molecular mechanisms that cut sequences of DNA from a chromosome, and other mechanisms that patch those sequences back into the DNA in other places. Such changes can affect the interactions of genes and so influence evolution. Other mechanisms will copy instead of cutting and will therefore provide the material for creating new genes. This book pays more attention to the molecular processes that make changes happen than to the evolutionary consequences of genetic changes and thus it complements a number of other books on the market.

Caporale, a medical researcher, gives special attention to bacteria and cancer on one side, and our bodies' defenses on the other. This gives examples that are relevant to readers' lives and also gives readers some insight into important medical issues. And, again, it means her book contains a lot of material that some other books don't have.

I see two minor weak points in the book. First, on page 130, she gives the impression that the material is a bit speculative, using such phrases as "I am convinced" and "the idea that I have proposed". In fact, as she says later in the book, specific gene mechanisms that make some mutations more likely than others are well known. Second, she uses "random" to mean that not all events are equally likely, even though there is nothing deterministic involved. I.e. there is no guiding power which says, e.g., "This DNA segment should be duplicated now." I mention these points because the text can easily be cited by creationists to cast doubt on the existence of evolution. But these don't detract from a very good book.

I found this book to be a very easy read and I feel certain that almost anyone who is thinking about buying this book will have no difficulty either. The main thing you need is a modest knowledge about genes. At least that is my judgment and, although my knowledge of evolution is rather extensive for a non-scientist, I think I have a good feel for what others can read. For more about this, click on my name, above, and read the "In My Own Words" section.

You might also be interested in other books about ways in which nature promotes evolution. I have listed several of these, along with some background information, in my Listmania list "Natural Processes That Promote Evolution", a link to which can be found by clicking on my name. These are books which I have reviewed and which I recommend.

[Added 31 Jan 2007] The first time through, I didn't pay close attention to the chapter on cancer. I read it again after I had developed a personal interest in cancer and had read a book entirely on the biology of cancer. Now I see this as an excellent chapter. Because cancer lives in a relatively simple ecosystem (e.g. my insides) and since it goes through a relatively small number of evolutionary steps, it is a good model to start with.

This is a excellent book. I've been fascinated by evolution, particularly after my course of study in Molecular Biology at UCSD. Although I have no doubts about the existance of evolution, I've come to have serious doubts about random mutations and natural selection as its primary driving force.

With the decoding of entire genomes, and the discovery of transposons and various errors in genome duplication, it is clear that far more than point mutation followed by natural sellection is at work.

This work gives an excellent accounting of the theory that mutation of the genome is not random.

Another book which presents a very similar belief is "Evolution:A Case Fot Stating The Obvious" by Derek Hough (Berkeley Pubblishing, 1997).

Together these books put to rest Darwinism and NeoDarwinism.

Contrary to the belief of many who read with glee books which show Darwin's short comings, these books do NOT refute evolution, but strengthen the "theory" of evolution by showing more clearly how evolution can happen. These views rely upon facts Darwin was never privy to.

Darwin's fame and rightful place in the area of natural history and biology is still assured for giving us "evolution." For his contribution to debunking the theory of the permanance of species prevalent in his day, he is owed a debt of gratitude and admiration.

I strongly recommend these books to anyone interested in biology or evolution, especially those neo-Darwinsit who might want to consider jumping ship before its too late.

Most accounts of Darwinism are conventional repetitions of tired phrases, and don't let on there is something new afoot in the specialized work of students of molecular evolution. This engaging work describes the processes of non-random mutation that are being discovered at work in the genome, and the result is an eye-opener.
As the author notes:

"The work described in this book has led me to the conclusion that natural selection must work not just on each individual mutation, but also on the very mechanisms that generate genetic variation-as it does on all bio- logical functions. The research discussed in this book leads to the conclusion that mutations are not all accidents and that mutations are not always random. Our genomes, and those of other life forms, have evolved mechanisms that create different kinds of mutations in their DNA, and they reuse and adapt useful pieces of DNA, even to the point that there are genomic 'interchangeable parts.'
Biochemical mechanisms can arise that tend to focus genetic variation, resulting in "hot spots" of genetic change at certain places in the genome."