Descoberto o mecanismo de DNA 'lixo' que impede o cruzamento de duas espécies

quarta-feira, outubro 28, 2009

Species-Specific Heterochromatin Prevents Mitotic Chromosome Segregation to Cause Hybrid Lethality in Drosophila

Patrick M. Ferree*, Daniel A. Barbash*
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America

Abstract Top
Postzygotic reproductive barriers such as sterility and lethality of hybrids are important for establishing and maintaining reproductive isolation between species. Identifying the causal loci and discerning how they interfere with the development of hybrids is essential for understanding how hybrid incompatibilities (HIs) evolve, but little is known about the mechanisms of how HI genes cause hybrid dysfunctions. A previously discovered Drosophila melanogaster locus called Zhr causes lethality in F1 daughters from crosses between Drosophila simulans females and D. melanogaster males. Zhr maps to a heterochromatic region of the D. melanogaster X that contains 359-bp satellite repeats, suggesting either that Zhr is a rare protein-coding gene embedded within heterochromatin, or is a locus consisting of the noncoding repetitive DNA that forms heterochromatin. The latter possibility raises the question of how heterochromatic DNA can induce lethality in hybrids. Here we show that hybrid females die because of widespread mitotic defects induced by lagging chromatin at the time during early embryogenesis when heterochromatin is first established. The lagging chromatin is confined solely to the paternally inherited D. melanogaster X chromatids, and consists predominantly of DNA from the 359-bp satellite block. We further found that a rearranged X chromosome carrying a deletion of the entire 359-bp satellite block segregated normally, while a translocation of the 359-bp satellite block to the Y chromosome resulted in defective Y segregation in males, strongly suggesting that the 359-bp satellite block specifically and directly inhibits chromatid separation. In hybrids produced from wild-type parents, the 359-bp satellite block was highly stretched and abnormally enriched with Topoisomerase II throughout mitosis. The 359-bp satellite block is not present in D. simulans, suggesting that lethality is caused by the absence or divergence of factors in the D. simulans maternal cytoplasm that are required for heterochromatin formation of this species-specific satellite block. These findings demonstrate how divergence of noncoding repetitive sequences between species can directly cause reproductive isolation by altering chromosome segregation.

Author Summary Top
Speciation is most commonly understood to occur when two species can no longer reproduce with each other, and sterility and lethality of hybrids formed between different species are widely observed causes of such reproductive isolation. Several protein-coding genes have been previously discovered to cause hybrid sterility and lethality. We show here that first generation hybrid females in Drosophila die during early embryogenesis because of a failure in mitosis. However, we have discovered that this is not a general failure in mitosis, because only the paternally inherited X chromosome fails to segregate properly. Our analyses further demonstrate that this mitotic failure is caused by a large heterochromatic region of DNA (millions of base pairs) that contains many repetitive copies of short noncoding sequences that are normally transcriptionally quiescent. Interestingly, this block of heterochromatin is only found in the paternal species. We suggest that a failure of the maternal species to package this paternally inherited DNA region into heterochromatin leads to mitotic failure and hybrid lethality. If this is a general phenomenon it may explain other examples of hybrid lethality in which F1 females die but F1 males survive.

Citation: Ferree PM, Barbash DA (2009) Species-Specific Heterochromatin Prevents Mitotic Chromosome Segregation to Cause Hybrid Lethality in Drosophila. PLoS Biol 7(10): e1000234. doi:10.1371/journal.pbio.1000234

Academic Editor: Mohamed A. F. Noor, Duke University, United States of America

Received: July 2, 2009; Accepted: September 21, 2009; Published: October 27, 2009

Copyright: © 2009 Ferree et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work was supported by National Institutes of Health (NIH) grant R01GM74737 (DAB) and NIH National Research Service Award postdoctoral fellowship F32GM080893 (PMF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Abbreviations: FISH, fluorescent in situ hybridization; HI, hybrid incompatibility; rDNA, ribosomal DNA; TE, transposable element; TopoII, Topoisomerase II

* E-mail: (PMF); (DAB)