Amongst 15 bird species, representative of 7 orders, recurrent breakages evocating the presence of fragile sites were detected in the chromosomes of the 5 species belonging to Passeriformes. These breaks appeared when 5-bromodeoxyuridine (BrdU) was added to the cell culture medium at a dose inefficient for inducing chromosome structure alterations in other birds and mammals. They involved, similarly in male and female, 3 loci on the Z chromosome of 3 Turdus species (Turdidae). Labeling by BrdU antibody confirmed the correlation between BrdU incorporation into DNA and breakage, especially around and in the sites of breakage. Thus, 3 BrdU-sensitive fragile sites were present in the Z chromosomes of these birds. Three fragile sites were also detected at different locations in the Z chromosomes of the European robin (Erithacus rubecula, Muscicapidae), suggesting that a structural rearrangement occurred during the evolution of Turdidae and Muscicapidae. Chromosome banding confirmed this interpretation. Finally, in the more distantly related species Parus major (Paridae), the almost acrocentric Z chromosome displayed a single BrdU-sensitive fragile site in its short arm, and the W appeared to be pulverized by BrdU incorporation. Although it cannot be excluded that the BrdU-sensitive fragile sites may be involved in rearrangements, their conservation in many species, and possibly all Passeriformes, provides evidence that they do not constitute a pejorative character during evolution.

Keywords:
BrdU sensitivity, Erithacus, Fragile sites, Parus, Turdus, Z chromosome
1.
Belterman RHR, De Boer LEM: A karyological study of 55 species of birds, including karyotypes of 39 species new to cytology. Genetica 65:39-82 (1984).
2.
Debatisse M, Le Tallec B, Letessier A, Dutrillaux B, Brison O: Common fragile sites: mechanisms of instability revisited. Trends Genet 28:22-32 (2012).
3.
de Oliveira EHC, Tagliarini MM, dos Santos MS, O'Brien PCM, Ferguson-Smith MA: Chromosome painting in three species of Buteoninae: a cytogenetic signature reinforces the monophyly of South American species. PLoS One 8:e70071 (2013).
4.
Derjusheva S, Kurganova A, Habermann S, Gaginskaya E: High chromosome conservation detected by comparative chromosome painting in chicken, pigeon and passerine birds. Chromosome Res 12:715-723 (2004).
5.
Di Berardino D, Iannuzzi L, Di Meo GP: Localization of BrdU-induced break sites in bovine chromosomes. Caryologia 36:285-292 (1983).
6.
Ellegren H, Smeds L, Burri R, Olason Pl, Backström N, et al: The genomic landscape of species divergence in Ficedula flycatchers. Nature 491:756-760 (2012).
7.
Gripenberg U, Huuhtanen S, Wessman M, Nieminen M: A fragile site in the X chromosome of the reindeer (Rangifer tarandus L). Genet Sel Evol 23, Suppl 1:135s-139s (1991).
8.
Hammar B: The karyotype of thirty-one birds. Hereditas 65:29-58 (1970).
9.
Helmrich A, Stout-Weider K, Hermann K, Schrock E, Heiden T: Common fragile sites are conserved features of human and mouse chromosomes and relate to large active genes. Genome Res 16:1222-1230 (2006).
10.
Hewett DR, Handt O, Hobson L, Mangelsdorf M, Eyre HJ, et al: FRA10B structure reveals common elements in repeat expansion and chromosomal fragile site genesis. Mol Cell 1:773-781 (1998).
11.
Kretschmer R, Gunski RJ, Garnero AV, Furo IO, O'Brien PCM, et al: Molecular cytogenetic characterization of multiple intrachromosomal rearrangements in two representatives of the genus Turdus (Turdidae, Passeriformes). PLoS One 9:e103338 (2014).
12.
Laine VN, Gossmann TI, Schachtschneider KM, Garroway CJ, Madsen O, et al: Evolutionary signals of selection on cognition from the great tit genome and methylome. Nat Commun 7:10474 (2016).
13.
Lin MS, Takabayashi T, Wilson MG, Marchese CA: An in vitro and in vivo study of a BrdU-sensitive fragile site in the Chinese hamster. Cytogenet Cell Genet 38:211-215 (1984).
14.
Nanda I, Schlegelmilch K, Haaf T, Schartl M, Schmid M: Synteny conservation of the Z chromosome in 14 avian species (11 families) supports a role for Z dosage in avian sex determination. Cytogenet Genome Res 122:150-156 (2008).
15.
Nie W, O'Brien PCM, Wang J, Su W, He K, et al: Multidirectional chromosome painting substantiates the occurrence of extensive genomic reshuffling within Accipitriformes. BMC Evol Biol 15:205 (2015).
16.
Nishida-Umehara C, Fujiwara A, Ogawa A, Mizuno S, Abe S, Yoshida MC: Differentiation of Z and W chromosomes revealed by replication banding and FISH mapping of sex-chromosome-linked DNA markers in the cassowary (Aves, Ratitae). Chromosome Res 7:635-640 (1999).
17.
Pentzold C, Shah SA, Hansen NR, Le Tallec B, Seguin-Orlando A, et al: FANCD2 binding identifies conserved fragile sites at large transcribed genes in avian cells. Nucleic Acids Res 46:1280-1294 (2018).
18.
Richard F, Gerbault-Seureau M, Douangboupha B, Keovichit K, Hugot JP, Dutrillaux B: Karyotype diversity suggests that Laonastes aenigmamus (Laotian rock rat) (Rodentia, Diatomyidae) is a multi-specific genus. Chromosome Res 24:379-392 (2016).
19.
Ruiz-Herrera A, Ponsà M, García F, Egozcue J, García M, et al: Fragile sites in human and Macaca fascicularis chromosomes are breakpoints in chromosome evolution. Chromosome Res 10:33-44 (2002).
20.
Schmid M, Enderle E, Schindler D, Schempp W: Chromosomal banding and DNA replication patterns in bird karyotypes. Cytogenet Genome Res 52:139-146 (1989).
21.
Smeets DF, van de Klundert FA: Common fragile sites in man and three closely related primate species. Cytogenet Cell Genet 53: 8-14 (1990).
22.
Stone DM, Stephens KE: Bromodeoxyuridine induces chromosomal fragile sites in the canine genome. Am J Med Genet 46:198-202 (1993).
23.
Sutherland GR, Baker E, Seshadri RS: Heritable fragile site on human chromosomes. V. A new class of fragile site requiring BrdU for expression. Am J Hum Genet 32:542-548 (1980).
24.
Voiculescu I, Back E, Schempp W: Homozygous condition for a BrdU-requiring fragile site on chromosome 12. Hum Genet 86:416-417 (1991).
25.
Warren WC, Clayton DF, Ellegren H, Arnold AP, Hillier LW, et al: The genome of a songbird. Nature 464:757-762 (2010).
26.
Zhang H, Freudenreich CH: An AT-rich sequence in human common fragile site FRA16D causes fork stalling and chromosome breakage in S. cerevisiae. Mol Cell 27:367-379 (2007).
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