Evidence for widespread reticulate evolution within human duplicons.
ABSTRACT Approximately 5% of the human genome consists of segmental duplications that can cause genomic mutations and may play a role in gene innovation. Reticulate evolutionary processes, such as unequal crossing-over and gene conversion, are known to occur within specific duplicon families, but the broader contribution of these processes to the evolution of human duplications remains poorly characterized. Here, we use phylogenetic profiling to analyze multiple alignments of 24 human duplicon families that span >8 Mb of DNA. Our results indicate that none of them are evolving independently, with all alignments showing sharp discontinuities in phylogenetic signal consistent with reticulation. To analyze these results in more detail, we have developed a quartet method that estimates the relative contribution of nucleotide substitution and reticulate processes to sequence evolution. Our data indicate that most of the duplications show a highly significant excess of sites consistent with reticulate evolution, compared with the number expected by nucleotide substitution alone, with 15 of 30 alignments showing a >20-fold excess over that expected. Using permutation tests, we also show that at least 5% of the total sequence shares 100% sequence identity because of reticulation, a figure that includes 74 independent tracts of perfect identity >2 kb in length. Furthermore, analysis of a subset of alignments indicates that the density of reticulation events is as high as 1 every 4 kb. These results indicate that phylogenetic relationships within recently duplicated human DNA can be rapidly disrupted by reticulate evolution. This finding has important implications for efforts to finish the human genome sequence, complicates comparative sequence analysis of duplicon families, and could profoundly influence the tempo of gene-family evolution.
Article: Increasing trends in hospitalization for atrial fibrillation in the United States, 1985 through 1999: implications for primary prevention.[show abstract] [hide abstract]
ABSTRACT: Atrial fibrillation, the most common sustained disturbance of heart rhythm, is associated with a 5-fold increase in the incidence of ischemic stroke. The National Hospital Discharge Survey was used to estimate the annual number and prevalence of hospitalizations with atrial fibrillation among men and women 35 years of age or older. From 1985 through 1999, hospitalizations increased from 154 086 to 376 487 for a first-listed diagnosis and from 787 750 to 2 283 673 for any diagnosis. Prevalence was higher among successive age groups. Age-standardized prevalence was consistently higher among men than women. In 1999, essential hypertension, ischemic heart disease, congestive heart failure, and diabetes were prominent coexisting conditions. The number of male patients discharged home decreased from 77% to 63%, whereas the number of discharges to long-term care increased from 9% to 15%; the corresponding values for women were 72% to 56% and 15% to 23%. A slight increase in discharges to short-term care was indicated, whereas no trends were noted for in-hospital mortality. Hospitalizations for atrial fibrillation have increased dramatically (2- to 3-fold) in recent years. The public health burden of atrial fibrillation is enormous and expected to continue to increase over the next decades. Primary prevention of atrial fibrillation must be recognized and pursued as a complementary management strategy for reducing cardiovascular morbidity and mortality.Circulation 09/2003; 108(6):711-6. · 14.74 Impact Factor
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ABSTRACT: Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6–8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.Nature 05/2004; 429(6990):369-374. · 36.28 Impact Factor