Instead of Cites, a Hot Site for "Cool" Genome Map

Instead of Cites, a Hot Site for "Cool" Genome Map

by Jeremy Cherfas

WHAT'S HOT IN BIOLOGY...

Rank	Paper	Citations This Period Nov-Dec 97	Rank Last Period Sep-Oct 97
1	Y. Feng, et al., "HIV-1 entry cofactor: Functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor," Science, 272(5263):872-7, 10 May 1996. [NIH, NIAID, Bethesda, MD] *UK757	62	1
2	C.J. Bult, et al., "Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii," Science, 273(5278):1058-73, 23 August 1996. [6 U.S. institutions] *VD428	61	2
3	H. Deng, et al., "Identification of a major co-receptor for primary isolates of HIV-1," Nature, 381(6584):661-6, 20 June 1996. [Howard Hughes Med. Inst., New York U. Med. Ctr., NY; Aaron Diamond AIDS Res. Ctr., Rockefeller U., NY; Stanford U. Med. Ctr., CA; U. Louisville Sch. Med., KY; DNAX Res. Inst., Palo Alto, CA] *UR979	55	3
4	T. Dragic, et al., "HIV-1 entry into CD4⁺ cells is mediated by the chemokine receptor CC-CKR-5," Nature, 381(6584):667-73, 20 June 1996. [Aaron Diamond AIDS Res. Ctr., Rockefeller U., NY; Progenics Pharmaceuticals, Inc., Tarrytown, NY] *UR979	55	4
5	C. Dib, et al., "A comprehensive genetic map of the human genome based on 5,264 microsatellites," Nature, 380(6570):152-4, 14 March 1996. [Genethon and CNRS URA 1922, Evry, France; INSERM U358, Hosp. Saint-Louis, Paris, France; CHU Laval, Quebec, Canada] *TZ978	53	†
6	M. Muzio, et al., "FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing sig- naling complex," Cell, 85(6):817-27, 14 June 1996. [U. Michigan Med. Sch., Ann Arbor; German Cancer Res. Ctr., Heidelberg; European Molec. Bio. Lab., Heidelberg; Human Genome Sci., Rockville, MD] *UR604	48	5
7	B.J. Doranz, et al., "A dual-tropic primary HIV-1 isolate that uses fusin and the b-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors," Cell, 85(7):1149-58, 28 June 1996. [U. Pennsylvania, Philadelphia; Free U. Brussels, Belgium; U. Louisville, KY] *UV484	48	10
8	G. Alkhatib, et al., "CC CKR5: A RANTES, MIP-1a, MIP-1b receptor as a fusion cofactor for macrophage-tropic HIV-1," Science, 272(5270):1955-8, 28 June 1996. [NIH, NIAID, Bethesda, MD] *UV294	47	7
9	F. Cocchi, et al., "Identification of RANTES, MIP-1a and MIP-1b as the major HIV-suppressive factors produced by CD8⁺ T cells," Science, 270(5243):1811-5, 15 December 1995. [NCI, Bethesda, MD; Advanced BioScience Labs, Kensington, MD; Inst. Human Virology, Baltimore, MD] *TK476	45	6
10	Z. Xia, et al., "Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis," Science, 270(5240):1326-31, 24 November 1995. [Childrens Hosp., Boston, MA: Harvard Med. Sch., Boston, MA; Howard Hughes Med. Inst, U. Massachusetts, Worcester] *TF899	44	†

SOURCE: ISI's Hot Papers Database. Read the full legend.

There's something very odd happening in our Hot Paper listing. Two things determine popularity: interest and utility. Interest is surely keeping HIV and apoptosis at the forefront. And, probably, the complete gene sequence of the archaeon bacterium Methanococcus jannaschii. But why has one map of the human genome been in the Top Ten almost without exception since it was published (Dib et al., paper #5), while another, older map has only just crept into notice at #14? (See T.J. Hudson, et al., "An STS-based map of the human genome," Science, 270[5244]:1945-54, 22 December 1995; 35 cites this period.)

Both are equally interesting, on the face of it, so it must be something to do with utility. At first sight, the more useful a piece of research is to the community at large, the more often it ought to be cited. But that is clearly not the reason.

The "hot" map, plotted by Jean Weissenbach at Généthon in France and his collaborators, locates 5,264 so-called microsatellites on the human genome. Microsatellites are sequences of DNA that vary considerably among individuals and can be used to identify stretches of chromosome. Généthon has built up a library that contains the entire human genome within about 30,000 volumes, each composed of a yeast artificial chromosome (YAC) that carries part of a human chromosome and some of the marker sequences. Researchers can use the microsatellites and the library to fish for the bits of DNA they are interested in.

The "cooler" map, assembled by Eric Lander (see this issue's lead story on page 1) and Thomas Hudson of the Whitehead-MIT Center for Genome Research, along with about 50 colleagues, consists of more than 15,000 landmarks-three times more than the microsatellite map. How they did it is an astonishing story, admirably described in the Science paper itself and an accompanying commentary (see p. 1919), but neither explains why one map is hot while the other is (relatively) not.

An obvious difference is the number of markers. That alone means the Hudson and Lander map can pinpoint genes with greater accuracy (and so is more useful). But a bigger difference is that the markers on the Hudson and Lander map are sequence-tagged sites (STSs), not microsatellites. An STS is a short sequence of DNA, roughly 200 to 500 base pairs long, which is unique on the genome. Researchers can use the sequence to manufacture primers that can then be used in the polymerase chain reaction (PCR) to amplify the DNA between any two STSs.

And that is crucial. To use microsatellites, researchers have to get their material-microsatellites and YAC library-from the Généthon group. To use STS markers, all they need to do is surf on over to a database on the World Wide Web, download the sequence, and program a primer-maker. Perhaps the need to acknowledge the provision of actual materials is a greater spur to citation than the free availability on the Internet of the sequence required to find a particular stretch of DNA.

The Whitehead Institute has maintained the web site since the project began, and it is certainly very popular: 50,000 visits a week is considered normal. That figure suggests that tracking website visits may soon become a better measure of a research group's worth than tracking citations. As Francis Collins, head of the National Human Genome Research Institute at the National Institutes of Health told Science, "You can't find anyone who is hunting genes who doesn't know the Whitehead World Wide Web address by heart." (In case you aren't one of the select few, it is http://www-genome.wi.mit.edu.)

Science writer Dr. Jeremy Cherfas works with the
Biotechnology and Biological Sciences Research Council of the U.K., Swindon.