biology's next top model
TRANSCRIPT
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the primitive crustacean classBranchipodia, specifically in theclam shrimp Eulimnadia texanaPopulations of these shrimpscomprise males and self-compatible hermaphrodites.
Previous studies havesuggested that the transition toandrodioecy in the clam shrimpmay have been a rather recentevent. But, because of the ancientorigins of the Branchiopodia,other have suggested a moreancient origin.
In the new study, the team hasstudied the reproductivestrategies of a number of speciesof shrimp within the genusEulimnadia from all continentswhere they occur. The actualnumber of species is currentlydebated but thought to bebetween 28 and 44. The teamreport data on 11 species and findthat nine showed definitiveevidence of androdioecy.
“Because these speciesrepresent a random subset of the28–44 species of Eulimnadia andare distributed across allcontinents that contain theshrimp, the most parsimoniousexplanation at present for thepreponderance of this breedingsystem in Eulimnadia is that itarose at or before the origin ofthis genus,” the authors report.
As widespread recent dispersalof these shrimps appears unlikely,the researchers have comparedpopulations with the history ofcontinental movements that mayhave separated previously closelyassociated populations. Suchancient separations, the authorsbelieve, have meant that theseclam shrimp have retainedandrodioecy through multiplespeciation events and across tensto hundreds of millions of years,suggesting “that in this genus,androdioecy has been a highlysuccessful and important mode ofreproduction.”
These results throw up freshfuel for the theoreticians. “Anytruly comprehensive modelseeking to delineate the benefitsof separation of the sexes relativeto hermaphroditism must nowexplain the long-lived coexistenceof males with hermaphrodites inthe Eulimnadia crustacea,” theauthors believe.Bookreview
Magazine R37
Book review
Biology’s next topmodel
Greg Gibson
The Dog and Its Genome —Edited by Elaine A. Ostrander, UrsGiger, and Kerstin Lindblad-Toh.(Monograph 44 of the Cold SpringHarbor Laboratory Press, ColdSpring Harbor, New York 2006).ISBN: 0-87969-742-3 (hardcover)
Anyone who loves dogs andmakes a living studying genomesis sure to enjoy a new collection ofreviews entitled ‘The Dog and ItsGenome’. A wide range of topics iscovered, from the role of dogs in amodern military to clinical trials forgene therapy, and from geneticdissection of congenital hipdysplasia to selection on cognitivefunction in silver foxes. Thequestion is, though, whether or notsomeone not so enamored withdogs is likely to find the subjectmatter interesting and compelling.This question is at the heart of thematter of whether the recentcompletion of the canine genomesequence will see the domesticdog take its place alongside thelaboratory mouse as anindispensable model for humandisease.
I put this question to one of myown shelties, Paddington. Helooked me straight in the eye andfirmly expressed his opinion thatthe real question is whether thehuman is a useful model for caninedisease? There are manyindications that it is, but certaindeficiencies of the human systemlimit their utility for identification ofsusceptibility factors for complexdisease. The first generation of thecanine haplotype map andincreasing interest in caninegenetics suggest that muchprogress is to be expected fromdirect study of a wide range ofbreeds.
The primary advantage of thedog for mapping complexdiseases is that the two-phaserecent history of the species,
involving initial domestication out-of-Asia approximately 40,000years ago, followed by very recentselection of over 200 breeds, hasleft a very convenient haplotypeblock structure. Within mostbreeds, it appears that thegenome can be regarded as amosaic of just ten thousandsegments, and this number oftagging polymorphisms (SNPs)should be sufficient to conduct awhole genome scan forassociation between genotype anddisease. That is about one tenththe number required for humans,though it remains to be seenwhether the density is ascomprehensive as theorysuggests. Subsequently, morefocused sampling across regionsin a collection of breeds promisesto refine 5 Mb intervals toindividual candidate genes, as theboundaries of haplotype blocksare thought to vary among breeds.This scheme is outlined nicely inthe book, in the chapter authoredby Lindblad-Toh and coworkers,who also provide a more detaileddescription of the 7.6X assemblyof the genome of a boxer as wellas initial observations of thecanine hapmap in a recent Naturepaper [1].
It is becoming apparent that thealleles that promote diseasesusceptibility are often unevenlydistributed across humanpopulations. This presents aconsiderable drawback forassociation mapping in humans,because of the so-calledpopulation stratification problem,and considerably reduces theirutility relative to Canis familiaris.The breed structure of domesticdogs not only provides aframework for study designs thatare relatively unaffected byadmixture, but also takesadvantage of the hypothesis thatmost common disease alleles havebeen captured by the inbreedingprocess. The biggest uncertainty,common to both dogs andhumans, is genetic heterogeneity:if different polymorphismscontribute to disease in differentpopulations or breeds,comparisons across these groupsare not informative. But many ofthe alleles of interest likely aroseprior to recent breed formation,
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Current Biology Vol 16 No 2R38
Q & A
Richard JorgensenRichard Jorgensen is in theDepartment of Plant Sciences atthe University of Arizona. Hiscurrent research interests includethe evolutionary diversification ofchromatin-based mechanisms forthe control of gene expression,especially those involving RNAinterference. He also currentlyserves as Editor-in-Chief of ThePlant Cell.
What turned you on to biology inthe first place? As an engineeringstudent in college, my interestswere drifting from nuclear physicsto chemistry to biochemistry when,in my third year, I took my first everbiology class, and suddenly the‘lights came on’. It was the lacoperon that did it, and geneticshas been my passion ever since.Believe it or not, I’d never beenexposed to biology previously,even in high school where theJesuit teachers, mainly interestedin philosophy and logic, pointed ustoward mathematics and physics,and placed a low relative value onbiology. Obviously, this was arather unfortunate miscalculationon their part and I’m sure it robbeda lot of promising students of anopportunity to consider arewarding and worthwhile careerpath in biology.
Do you have a scientific hero?Barbara McClintock, because shenever let anything or anybodystand in the way of pursuingresearch that she believed to beimportant and worthwhile. Herlove of science, heropenmindedness, and the wayshe balanced scientificallyrigorous analysis with intuitionand creative thought have longbeen an inspiration to me.
What paper influenced youmost? Unquestionably that wouldbe R. Alexander Brink’s 1960article ‘Paramutation andchromosome organization’ (Q.Rev. Biol. 35, 120), in which heproposed that chromosomes havea ‘paragenetic’ function in addition
and the well-known tendency ofparticular maladies to show breed-specificity can be used to inferlikely sharing of descent of thecausative alleles. As made clear inthe volume under review, this is astrue of major-gene diseases suchas copper toxicosis and variousretinopathies, as it is of the morecomplex and more prevalentcardiomyopathies, cancers, anddermatitis.
Conduction of clinical trials isalso much more difficult inhumans. Human healthcare isexpensive, and members of thisspecies show a predilectiontoward law suits when things don’tgo quite right. By contrast, dogtrials can be relatively quick toperform, study populations arefairly easily recruited, and it turnsout the physiology andendocrinology of disease is oftenstrikingly similar between the largemammals. Though not discussedin the volume, pharmacogeneticsmay get a boost from dogs, asrefractoriness to drugs oftendisplays similar levels as observedin humans — for example,veterinarians will tell you thatapproximately ten percent ofepileptics are non-responsive tothe commonly usedpharmacological agents — andthere is less of the litigiousdownside to mis-prediction. Genetherapy, too, has definite upsidesin canines as various gene deliveryapproaches can be assessed indogs for many treatable raredisorders that can actually be bredin study colonies.
Why not mice? The simpleanswer is that most of the complexdiseases we see in dogs arenaturally occurring, as opposed tohaving been engineered into cagedanimals. Our pets share ourtoxicological and, to some extent,nutritional environment, and thesimilarities in the time of onset andetiology of so many of the majordiseases is striking. It turns out,too, that our genomes are moresimilar at the level of gene contentand sequence than those ofrodents, even though rodentsshare a more recent commonancestor with Homo sapiens thando dogs. This is because of anaccelerated rate of divergence inthe smaller mammals.
Nevertheless, many biomedicalresearchers, particularly those whoserve on study sections, will pointout that there are few remaininglimits to gene discovery in humans,and what we really need is a modelorganism that we can manipulategenetically in order to test specifichypotheses. Transgenic dogsexpressing GFP-tagged proteinsaren’t likely to be running aroundany time soon — though a dogwith fluorescent green eyes maygo down well with children — whilebiochemistry and molecular cellbiology lag well behind the mouse.Dogs are unlikely ever to become amodel for the annotation of genefunction.
Which brings us back to thereason why there are dogs in thefirst place: they are physicallydiverse and attractive, andbehaviorally fascinating and useful.Another reason to buy The Dogand its Genome is for the superb28-page appendix of paintings of145 breeds. It is remarkable giventhe variety of shapes and sizeshow little attention evolutionarydevelopmental biologists havegiven to the species. Aside from afew groups performing quantitativetrait loci (QTL) mapping withinbreeds, there is little data on thegenetic basis of allometricdifferentiation, despite the fact thatsuch studies are likely to provide aperspective quite distinct from theone derived from comparison ofinvertebrate development [2].Regarding behavior, dogs are evenmore compelling. Whether it isherding tendencies or separationanxiety, the neurochemistry ofseizures, or simply the biology ofunconditional love, dogs presentopportunities for study that aresecond to none.
References1. Lindblad-Toh, K., Wade, C.M., Mikkelsen,
T.S., Karlsson, E.K., Jaffe, D.B., Kamal,M., Clamp, M., Chang, J.L., Kulbokas,E.J., 3rd, Zody, M.C., et al. (2005).Genome sequence, comparative analysis,and haplotype structure of the domesticdog. Nature 438, 803–819.
2. Carroll, S.B. (2005). Endless Forms MostBeautiful: The New Science of Evo Devoand the Making of the Animal Kingdom.Norton and Co., New York.
Department of Genetics, Gardner Hall,North Carolina State University, Raleigh,North Carolina 27695-7614, USA.E-mail: [email protected]