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TRENDS in Genetics Vol.17 No.8 August 2001
http://tig.trends.com 0168–9525/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.
443News&Comment
Letter
An ancient cluster ofWnt paraloguesThe recently completed sequences of thehuman and Drosophila genomes reveal aninteresting conserved arrangement of agroup of Wnt genes1. There are seven Wntfamily members in Drosophila and 19 inthe human genome. I aligned their proteinsequences using the ClustalW program(shown on http://www.stanford.edu/~rnusse/genealigns/wntalign.html). The alignment confirmed an earlierphylogenic analysis2 of vertebrate andDrosophilaWnt proteins that indicated anorthologous relationship between WNT1and DrosophilaWingless3 (Wg); betweenWNT7 and DWnt2; and between WNT5 and DWnt5. Three recently identifiedDrosophilaWnt proteins also have orthologsin the human genome and are thereforecalled DWnt6, DWnt8 and DWnt10.
In the Drosophila genome, theparalogous genes wg, DWnt6 and DWnt10
are immediately adjacent to each other atposition 27F on the second chromosome,transcribed in the same orientation andwith no recognizable gene in between them.This order is conserved in the humangenome. Human chromosome 12q13contains WNT1 and WNT10B immediatelyadjacent to one another, although they aretranscribed in the opposite orientation.Human chromosome 2q35 has WNT6 nextto WNT10A, expressed from the samestrand with no gene in between. WNT10Aand WNT10B are closely related to eachother, and the result of recent duplicationsoccurred during the evolution of the jawedvertebrate lineage2. It seems probable,therefore, that there was a commonancestral cluster of Wnt genes containingWNT1, WNT6 and WNT10 pre-dating thelast common ancestor of arthropods anddeuterostomes. This cluster has beenpreserved during arthropod evolution. In the lineage leading to vertebrates, the cluster was duplicated, leading to the WNT1–WNT6–WNT10A and
WNT1–WNT6–WNT10B groups now onhuman chromosomes 12 and 2 (Fig. 1).After this duplication, WNT1 was lost fromone cluster and WNT6 from the other.
This conservation of gene order isreminiscent of the evolutionaryconservation of the Hox complex4 and couldbe similarly ancient (500 Myr old). None ofthe remaining Wnt genes in either the fly orthe human are organized in a similar way.Although the Drosophila Wnt4 gene is closeto wg, there is one gene (CG13785) inbetween. The DWnt2, DWnt8 and DWnt5genes are at separate locations. In thehuman genome, there are some additionalexamples of closely linked Wnt genes(WNT3A–WNT14 on 1q42; WNT2–WNT16on 7q31; and WNT3–WNT15 on 17q21),but there are intervening genes in eachcase. The conservation of theWNT1–WNT6–WNT10 cluster mightimply that these genes are, like Hox geneclusters, coordinately regulated.
Roel Nusse
Howard Hughes Medical Institute, Dept of Developmental Biology, Stanford University Medical School,Stanford, CA 94305-5323, USA.e-mail: [email protected]
References
1 Cadigan, K. and Nusse, R. (1997) Wnt signaling: acommon theme in animal development. GenesDev. 11, 3286–3305
2 Sidow, A. (1992) Diversification of the Wnt genefamily on the ancestral lineage of vertebrates.Proc. Natl. Acad. Sci. U. S. A. 89, 5098–5102
3 Rijsewijk, F. et al. (1987) The Drosophilahomolog ofthe mouse mammary oncogene int-1 is identical tothe segment polarity gene wingless. Cell50,649–657
4 Duboule, D. and Morata, G. (1994) Colinearityand functional hierarchy among genes of thehomeotic complexes. Trends Genet. 10, 358–364
Reawakening the telomeresThe gradual erosion of the ends ofchromosomes (telomeres) during successivecell divisions has long been associated withaging, but possible mechanisms linking thetwo processes have eluded scientists, untilnow. Bits of DNA are lost from telomeresduring each cell division. When their telomeresbecome too short, cells stop dividing. Somecells, including 90% of cancerous cells, possessthe enzyme telomerase that maintains theirtelomeres, allowing them to continue growing.Most cells, however, lack telomerase.
Now, Baur et al. have discovered aninteresting phenomenon in some humancell lines: telomere position effect (TPE),whereby gene expression is turned off inthe regions near telomeres. This TPEsilencing is stronger in cells with longertelomeres. The researchers speculate thatTPE can act as an age-sensing mechanism.As telomeres become shorter, some genesthat were previously silent will becomeexpressed again. Could this reactivationallow the cell to change its behavior beforebecoming senescent? [Baur, J.A. et al.(2001) Science 292, 2075–2077] NJ
TRENDS in Genetics
WNT1
wg DWnt6 DWnt10
WNT1 WNT10B
WNT6 WNT10A
WNT6 WNT10
Primordial cluster
Drosophila 27F
Human 12q13
Human 2q35
Fig.1. A primordial cluster of three Wnt genes is present in the Arthropod lineage and in Drosophila. The human genomecontains duplicated copies of the same cluster but WNT6 is deleted from 12q13 and WNT1 is deleted from 2q35. Becausethe common ancestral cluster pre-dates the last common ancestor of arthropods and deuterostomes, it is ~500 Myr old.
Steven G. Gray
[email protected] Holding
[email protected] Isles
[email protected] Ligoxygakis
[email protected] Pandey
[email protected] Johnson
