Biomedical subjects

Luigi Viggiano

Publications and source records attributed to Luigi Viggiano.

6 recordsLinked to original sources

PubMed2005

Evidence for widespread reticulate evolution within human duplicons.

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.

Computational Biology↗

PubMed2005

Progressive proximal expansion of the primate X chromosome centromere.

Previous studies of the pericentromeric region of the human X chromosome short arm (Xp) revealed an age gradient from ancient DNA that contains expressed genes to recent human-specific DNA at the functional centromere. We analyzed the finished sequence of this human genomic region to investigate its evolutionary history. Phylogenetic analysis of >1,500 alpha-satellite monomers from the region revealed the presence of five physical domains, each containing monomers from a distinct phylogenetic clade. The most distal domain contains long interspersed nucleotide element repeats that were active >35 million years ago, whereas the four proximal domains contain more recently active long interspersed nucleotide element repeats. An out-of-register, unequal recombination (i.e., crossover) detected at the edge of the X chromosome-specific alpha-satellite array (DXZ1) may reflect the most recent of a series of punctuating events during evolution that resulted in a proximal physical expansion of the X centromere. The first 18 kb of this array has 97-99% pairwise identity among all 2-kb repeat units. To perform more detailed evolutionary comparisons, we sequenced the junction between the ancient DNA of Xp and the primate-specific alpha satellite in chimpanzee, gorilla, orangutan, vervet, macaque, and baboon. The striking conservation found in all cases supports the ancestral nature of the alpha satellite at this location. These studies demonstrate that the primate X centromere appears to have evolved through repeated expansion events occurring within the central, active region of centromeric DNA, with the newly added sequences then conferring centromere function.

Animals↗

PubMed2005

Energy biogenesis: one key for coordinating two genomes.

In metazoan organisms, energy production is the only example of a process that is under dual genetic control: nuclear and mitochondrial. We used a genomic approach to examine how energy genes of both the nuclear and mitochondrial genomes are coordinated, and discovered a novel genetic regulatory circuit in Drosophila melanogaster that is surprisingly simple and parsimonious. This circuit is based on a single DNA regulatory element and can explain both intra- and inter-genomic coordinated expression of genes involved in energy production, including the full complement of mitochondrial and nuclear oxidative phosphorylation genes, and the genes involved in the Krebs cycle.

Animals↗

PubMed2003

Genomic sequence and transcriptional profile of the boundary between pericentromeric satellites and genes on human chromosome arm 10p.

Contiguous finished sequence from highly duplicated pericentromeric regions of human chromosomes is needed if we are to understand the role of pericentromeric instability in disease, and in gene and karyotype evolution. Here, we have constructed a BAC contig spanning the transition from pericentromeric satellites to genes on the short arm of human chromosome 10, and used this to generate 1.4 Mb of finished genomic sequence. Combining RT-PCR, in silico gene prediction, and paralogy analysis, we can identify two domains within the sequence. The proximal 600 kb consists of satellite-rich pericentromerically duplicated DNA which is transcript poor, containing only three unspliced transcripts. In contrast, the distal 850 kb contains four known genes (ZNF248, ZNF25, ZNF33A, and ZNF37A) and up to 32 additional transcripts of unknown function. This distal region also contains seven out of the eight intrachromosomal duplications within the sequence, including the p arm copy of the approximately 250-kb duplication which gave rise to ZNF33A and ZNF33B. By sequencing orthologs of the duplicated ZNF33 genes we have established that ZNF33A has diverged significantly at residues critical for DNA binding but ZNF33B has not, indicating that ZNF33B has remained constrained by selection for ancestral gene function. These results provide further evidence of gene formation within intrachromosomal duplications, but indicate that recent interchromosomal duplications at this centromere have involved transcriptionally inert, satellite rich DNA, which is likely to be heterochromatic. This suggests that any novel gene structures formed by these interchromosomal events would require relocation to a more open chromatin environment to be expressed.

Amino Acid Sequence↗

PubMed2002

Human paralogs of KIAA0187 were created through independent pericentromeric-directed and chromosome-specific duplication mechanisms.

KIAA0187 is a gene of unknown function that maps to 10q11 and has been subject to recent duplication events. Here we analyze 18 human paralogs of this gene and show that paralogs of exons 14-23 were formed through satellite-associated pericentromeric-directed duplication, whereas paralogs of exons 1-9 were created via chromosome-specific satellite-independent duplications. In silico, Northern, and RT-PCR analyses indicate that nine paralogs are transcribed, including four in which KIAA0187 exons are spliced onto novel sequences. Despite this, no new genes appear to have been created by these events. The chromosome 10 paralogs map to 10q11, 10q22, 10q23.1, and 10q23.3, forming part of a complex family of chromosome-specific repeats that includes GLUD1, Cathepsin L, and KIAA1099 pseudogenes. Phylogenetic analyses and comparative FISH indicates that the 10q23.1 and 10q23.3 repeats were created in 10q11 and relocated by a paracentric inversion 13 to 27 Myr ago. Furthermore, the most recent duplications, involving the KIAA1099 pseudogenes, have largely been confined to 10q11. These results indicate a simple model for the evolution of this repeat family, involving multiple rounds of centromere-proximal duplication and dispersal through intrachromosomal rearrangement. However, more complex events must be invoked to account for high sequence identity between some paralogs.

Animals↗

PubMed2001

Human-specific duplication and mosaic transcripts: the recent paralogous structure of chromosome 22.

In recent decades, comparative chromosomal banding, chromosome painting, and gene-order studies have shown strong conservation of gross chromosome structure and gene order in mammals. However, findings from the human genome sequence suggest an unprecedented degree of recent (<35 million years ago) segmental duplication. This dynamism of segmental duplications has important implications in disease and evolution. Here we present a chromosome-wide view of the structure and evolution of the most highly homologous duplications (> or = 1 kb and > or = 90%) on chromosome 22. Overall, 10.8% (3.7/33.8 Mb) of chromosome 22 is duplicated, with an average sequence identity of 95.4%. To organize the duplications into tractable units, intron-exon structure and well-defined duplication boundaries were used to define 78 duplicated modules (minimally shared evolutionary segments) with 157 copies on chromosome 22. Analysis of these modules provides evidence for the creation or modification of 11 novel transcripts. Comparative FISH analyses of human, chimpanzee, gorilla, orangutan, and macaque reveal qualitative and quantitative differences in the distribution of these duplications--consistent with their recent origin. Several duplications appear to be human specific, including a approximately 400-kb duplication (99.4%-99.8% sequence identity) that transposed from chromosome 14 to the most proximal pericentromeric region of chromosome 22. Experimental and in silico data further support a pericentromeric gradient of duplications where the most recent duplications transpose adjacent to the centromere. Taken together, these data suggest that segmental duplications have been an ongoing process of primate genome evolution, contributing to recent gene innovation and the dynamic transformation of genome architecture within and among closely related species.

Animals↗