Patterns of Segmental Duplication in the Human Genome

Abstract

We analyzed the completed human genome for recent segmental duplications (size > or = 1 kb and sequence similarity > or = 90%). We found that approximately 4% of the genome is covered by duplications and that the extent of segmental duplication varies from 1% to 14% among the 24 chromosomes. Intrachromosomal duplication is more frequent than interchromosomal duplication in 15 chromosomes. The duplication frequencies in pericentromeric and subtelomeric regions are greater than the genome average by approximately threefold and fourfold. We examined factors that may affect the frequency of duplication in a region. Within individual chromosomes, the duplication frequency shows little correlation with local gene density, repeat density, recombination rate, and GC content, except chromosomes 7 and Y. For the entire genome, the duplication frequency is correlated with each of the above factors. Based on known genes and Ensembl genes, the proportion of duplications containing complete genes is 3.4% and 10.7%, respectively. The proportion of duplications containing genes is higher in intrachromosomal than in interchromosomal duplications, and duplications containing genes have a higher sequence similarity and tend to be longer than duplications containing no genes. Our simulation suggests that many duplications containing genes have been selectively maintained in the genome.

Timing and mechanism of ancient vertebrate genome duplications – the adventure of a hypothesis

“…The 2R paralogons with an average size of 0.7 Mb [25] are strikingly larger than the recently duplicated segments in the human genome (sequence similarity R90%, average size of 14.7-18.5 kb) [47]. Among the largest paralogons detected are a 41-Mb and 20-Mb region shared on chromosomes 1 and 9.…”

Regulation of mammalian gene expression by retroelements and non‐coding tandem repeats

“…On the other hand, the frequency of segmental duplications along human chromosomes does not correlate at all with density of repeats. (81) Analysis of human LINE1 showed that there is no significant changes of their relative distribution in GC-rich and AT-rich DNA over the past 100 Myr, in contrast to significant changes seen for Alu. (19) Together, these data argue against the hypothesis that explains SINE clustering near genes by an excess of neutral segmental duplications over deletions in gene-rich regions.…”

“…(19,76) This indicates that the clustering of the major Alu subfamilies in gene-rich regions is unlikely to be a consequence of positive selection of their initial insertions (84) but it can arise through secondary genome rearrangements. (79) These rearrangements may have been fixed in populations through random genetic drift (80,81) or because of a population bottleneck (85) but it seems unlikely that similar neutral rearrangements were fixed in the human and mouse lineages. Negative selection of L1 elements in gene-rich segments is found to be a consequence of their ability to mediate ectopic recombination (82) and positive selection of SINEs may be caused by effects of SINE transcripts (86) or by SINE-associated transcription regulatory motifs (see above).…”

Diagnosing duplications – can it be done?

“…Because reports conflict on the gene content of LCRs [20,21,[67][68][69][70], depending on methodology, species and the quality of the data, it is not clear to what extent LCRs have a role in the duplication of entire genes. However, there is substantial evidence that LCRs contain fragments of coding sequence and are likely to be the sites of new gene formation by domain shuffling.…”