Tài liệu Báo cáo khoa học: cN-crystallin and the evolution of the bc-crystallin superfamily in

cN-crystallin and the evolution of the bc-crystallin

superfamily in vertebrates

Graeme Wistow1

, Keith Wyatt1

, Larry David2

, Chun Gao1

, Orval Bateman3

, Steven Bernstein4

,

Stanislav Tomarev1

, Lorenzo Segovia5

, Christine Slingsby3 and Thomas Vihtelic6

1 National Eye Institute, National Institutes of Health, Bethesda, MD, USA

2 Oregon Health Sciences University, Portland, OR, USA

3 Department of Crystallography, Birkbeck College, London, UK

4 Department of Ophthalmology, University of Maryland School of Medicine, Baltimore, MD, USA

5 IBT ⁄ UNAM, Col. Chamilpa, Cuernavaca, Morelos, Mexico

6 Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA

Much of the complexity and diversity of life arises

from the multiplication and evolution of gene famil￾ies, increasing the functional repertoire of the gen￾ome. By gene duplication, a single protein function

(or set of functions) can be expanded into a broader

set of more specialized functions. The c-crystallins

are a gene family with a complex history in verteb￾rate evolution. They encode proteins that are highly

abundant components of the eye lens but are also

expressed at lower levels in other parts of the eye,

perhaps with a stress-like role [1–6]. Together with

the related b-crystallins, the c-crystallins belong to an

ancient superfamily (known as the bc-crystallin super￾family) with members ranging from the prokaryotic

sporulation protein, Protein S of Myxococcus xanthus

[7], to AIM1, a protein implicated in the control of

malignancy in melanoma in man [8,9]. In the verteb￾rate lens, the b and c crystallins together account for

the majority of the soluble proteins (the other major

family being the a-crystallins, members of the small

heat-shock protein superfamily [10,11]). Although it

has been suggested that proteins of this superfamily

may have roles in maintenance of cellular architec￾ture [8], little is known about their function. Like the

c-crystallins, b-crystallins have also been detected in

the retina [12], and both have been identified in Dru￾sen bodies, which form with age in retinal pigment

epithelium (RPE) [13].

Keywords

crystallin; eye; gene structure; intron loss;

lens

Correspondence

G. Wistow, Section on Molecular Structure

and Functional Genomics, National Eye

Institute, Bg 7, Rm 201, National Institutes

of Health, Bethesda, MD 20892-0703, USA

Tel: +1 301 402 3452

Fax: +1 301 496 0078

E-mail: [email protected]

(Received 21 January 2005, revised 23

February 2005, accepted 8 March 2005)

doi:10.1111/j.1742-4658.2005.04655.x

The b and c crystallins are evolutionarily related families of proteins that

make up a large part of the refractive structure of the vertebrate eye lens.

Each family has a distinctive gene structure that reflects a history of succes￾sive gene duplications. A survey of c-crystallins expressed in mammal, rep￾tile, bird and fish species (particularly in the zebrafish, Danio rerio) has led

to the discovery of cN-crystallin, an evolutionary bridge between the b and

c families. In all species examined, cN-crystallins have a hybrid gene struc￾ture, half b and half c, and thus appear to be the ‘missing link’ between

the b and c crystallin lineages. Overall, there are four major classes of

c-crystallin: the terrestrial group (including mammalian cA–F); the aquatic

group (the fish cM-crystallins); the cS group; and the novel cN group. Like

the evolutionarily ancient b-crystallins (but unlike the terrestrial cA–F and

aquatic cM groups), both the cS and cN crystallins form distinct clades

with members in fish, reptiles, birds and mammals. In rodents, cN is

expressed in nuclear fibers of the lens and, perhaps hinting at an ancestral

role for the c-crystallins, also in the retina. Although well conserved

throughout vertebrate evolution, cN in primates has apparently undergone

major changes and possible loss of functional expression.

Abbreviations

EST, expressed sequence tag; RPE, retinal pigment epithelium.

2276 FEBS Journal 272 (2005) 2276–2291 ª 2005 FEBS