Article

Evidence for widespread reticulate evolution within human duplicons.

Institute of Human Genetics, University of Newcastle upon Tyne, International Centre for Life, Newcastle upon Tyne, United Kingdom.
The American Journal of Human Genetics (impact factor: 10.6). 12/2005; 77(5):824-40. DOI:10.1086/497704 pp.824-40
Source: PubMed

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.

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Keywords

24 human duplicon families
 
30 alignments
 
>20-fold excess
 
comparative sequence analysis
 
duplicon families
 
gene conversion
 
gene innovation
 
human duplications
 
human genome sequence
 
includes 74 independent tracts
 
multiple alignments
 
perfect identity >2 kb
 
phylogenetic relationships
 
phylogenetic signal consistent
 
segmental duplications
 
sharp discontinuities
 
span >8 Mb
 
specific duplicon families
 
total sequence shares 100% sequence identity
 
unequal crossing-over