Conditions for the Evolution of Gene Clusters in Bacterial Genomes

Genes encoding proteins in a common pathway are often found near each other along bacterial chromosomes. Several explanations have been proposed to account for the evolution of these structures. For instance, natural selection may directly favour gene clusters through a variety of mechanisms, such as increased efficiency of coregulation. An alternative and controversial hypothesis is the selfish operon model, which asserts that clustered arrangements of genes are more easily transferred to other species, thus improving the prospects for survival of the cluster. According to another hypothesis (the persistence model), genes that are in close proximity are less likely to be disrupted by deletions. Here we develop computational models to study the conditions under which gene clusters can evolve and persist. First, we examine the selfish operon model by re-implementing the simulation and running it under a wide range of conditions. Second, we introduce and study a Moran process in which there is natural selection for gene clustering and rearrangement occurs by genome inversion events. Finally, we develop and study a model that includes selection and inversion, which tracks the occurrence and fixation of rearrangements. Surprisingly, gene clusters fail to evolve under a wide range of conditions. Factors that promote the evolution of gene clusters include a low number of genes in the pathway, a high population size, and in the case of the selfish operon model, a high horizontal transfer rate. The computational analysis here has shown that the evolution of gene clusters can occur under both direct and indirect selection as long as certain conditions hold. Under these conditions the selfish operon model is still viable as an explanation for the evolution of gene clusters

Aberrant methylation of the Adenomatous Polyposis Coli (APC) gene promoter is associated with the inflammatory breast cancer phenotype

Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter occurs in about 40% of breast tumours and has been correlated with reduced APC protein levels. To what extent epigenetic alterations of the APC gene may differ according to specific breast cancer phenotypes, remains to be elucidated. Our aim was to explore the role of APC methylation in the inflammatory breast cancer (IBC) phenotype. The status of APC gene promoter hypermethylation was investigated in DNA from normal breast tissues, IBC and non-IBC by both conventional and real-time quantitative methylation-specific PCR (MSP). APC methylation levels were compared with APC mRNA and protein levels. Hypermethylation of the APC gene promoter was present in 71% of IBC samples (n=21) and 43% of non-IBC samples (n=30) by conventional MSP (P=0.047). The APC gene also showed an increased frequency of high methylation levels in IBC (in 74% of cases, n=19) vs non-IBC (in 46% of cases, n=35) using a qMSP assay (P=0.048). We observed no significant association between APC methylation levels by qMSP and APC mRNA or protein expression levels. In conclusion, for the first time, we report the association of aberrant methylation of the APC gene promoter with the IBC phenotype, which might be of biological and clinical importance

HLA antigens in severe pre-eclampsia.

When the HLA types of 80 pre-eclamptic women and their husbands and 83 control couples were compared significantly more pre-eclamptic women had only one identifiable HLA B antigen, and were presumed to be homozygous at this locus. Those who were homozygous for HLA B were more likely to be homozygous for HLA A as well, and more likely to be homozygous for HLA A as well, and to have more severe pre-eclampsia. There was neither increased HLA incompatibility nor greater antigen-sharing between pre-eclamptic women and their husbands, but maternal HLA A and B homozygosity reduced the number of antigenic disparities between pre-eclamptic women and their husbands. The data are consistent with the hypothesis that maternal recessive immune-response genes may contribute to the development of pre-eclampsia. Alternatively maternal HLA homozygosity may predispose to fetal changes comparable to runting

HLA antigens in severe pre-eclampsia.

When the HLA types of 80 pre-eclamptic women and their husbands and 83 control couples were compared significantly more pre-eclamptic women had only one identifiable HLA B antigen, and were presumed to be homozygous at this locus. Those who were homozygous for HLA B were more likely to be homozygous for HLA A as well, and more likely to be homozygous for HLA A as well, and to have more severe pre-eclampsia. There was neither increased HLA incompatibility nor greater antigen-sharing between pre-eclamptic women and their husbands, but maternal HLA A and B homozygosity reduced the number of antigenic disparities between pre-eclamptic women and their husbands. The data are consistent with the hypothesis that maternal recessive immune-response genes may contribute to the development of pre-eclampsia. Alternatively maternal HLA homozygosity may predispose to fetal changes comparable to runting

Reproductive biology of female Amazonian brocket deer in northeastern Peru

The aim of this study was to provide information on the reproductive biology of brocket deer. Hence, we analyzed female reproductive tracts collected by rural hunters from 1991 to 1998 in the Tamshiyacu-Tahuayo Communal Reserve, northeastern Peruvian Amazon. We characterized the basic reproductive biology of brocket deer, analyzed whether the distributions of conceptions and births are aseasonal, and compared their reproductive productivity in two different areas subject to heavy and slight hunting pressures, respectively. We found that: (1) red and gray brocket deer did not differ in ovulation, fertilization, and pregnancy rates; (2) average number of fetuses per birth was 1.2 for red brocket deer and one for gray brocket deer; (3) sex of fetuses suggests a male biased sex ratio for both species; (4) neither species shows reproductive seasonality; and (5) gross productivity does not differ between heavily and slightly hunted areas. Our results indicate that brocket deer exhibit reproductive characteristics similar to their conspecifics in other parts of their native distribution range