Ultraconserved Elements in the Human Genome

  title={Ultraconserved Elements in the Human Genome},
  author={Gill Bejerano and Michael Pheasant and Igor V. Makunin and Stuart Stephen and W. James Kent and John S. A. Mattick and David Haussler},
  pages={1321 - 1325}
There are 481 segments longer than 200 base pairs (bp) that are absolutely conserved (100% identity with no insertions or deletions) between orthologous regions of the human, rat, and mouse genomes. Nearly all of these segments are also conserved in the chicken and dog genomes, with an average of 95 and 99% identity, respectively. Many are also significantly conserved in fish. These ultraconserved elements of the human genome are most often located either overlapping exons in genes involved in… 

Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants

It is shown that UCEs are significantly depleted among segmental duplications and copy number variants, indicating, along with other findings presented, that U CEs overlapping exons represent a distinct subset.

Highly Constrained Intergenic Drosophila Ultraconserved Elements Are Candidate ncRNAs

It is concluded that Drosophila species are rich with UCEs and that many of them may correspond to novel noncoding RNAs, particularly those within coding sequences likely to correspond to sites of ADAR-dependent RNA editing.

Large-scale appearance of ultraconserved elements in tetrapod genomes and slowdown of the molecular clock.

There was a massive genome-wide acquisition and expansion of UCEs during tetrapod and then amniote evolution, accompanied by a slowdown of the molecular clock, particularly in the amniotes, a process consistent with their functional exaptation in these lineages.

Ultraconserved Elements (UCEs) in the Human Genome

Human genome contains ultraconserved elements (UCEs) that are 200 bp or longer and 100% identical in mouse and rat genomes and UCEs have experienced high purifying selection, possibly due to the ‘multiplexing’ of multiple functions on the same element.

Ultraconserved elements in insect genomes: a highly conserved intronic sequence implicated in the control of homothorax mRNA splicing.

Real-time quantitative PCR analysis of different hth splice isoforms and Northern blotting showed that the conserved element is associated with a high incidence of intron retention in hth pre-mRNA, suggesting that the Conserved intronic element is critically important in the post-transcriptional regulation of hth expression in Diptera.

Multiple organism algorithm for finding ultraconserved elements

The algorithm is significantly faster than BLAST and is designed to handle very large genomes efficiently, and shows how a compromise design with a trade-off of disk space versus memory space allows for efficient computation while only requiring modest computer resources, and at the same time providing benefits not available with other software.

Human Genome Ultraconserved Elements Are Ultraselected

Analysis of the derived allele frequency spectrum shows that ultraconserved regions in the human genome are in fact under negative selection that is much stronger than that in protein coding genes.

Ultraconserved Elements Between the Genomes of the Plants Arabidopsis thaliana and Rice

Compared the genomes of Arabidopsis thaliana and rice, which diverged about 200 million years ago, and identified 25 ultraconserved elements that are longer than 100 bp, but the functions of these plant ultraconserve elements and the reasons why they are practically frozen during the evolution of millions of years remain a mystery.

Identification and characterization of new long conserved noncoding sequences in vertebrates

The results suggest that mutations occur with equal frequency in LCNS but are eliminated by natural selection during the course of evolution.

Highly Conserved Non-Coding Sequences Are Associated with Vertebrate Development

A whole-genome comparison between humans and the pufferfish, Fugu rubripes, is used to identify nearly 1,400 highly conserved non-coding sequences, which are likely to form part of the genomic circuitry that uniquely defines vertebrate development.



Evolutionarily conserved sequences on human chromosome 21.

The utility of high-density oligonucleotide arrays are described as a rapid approach for comparing human sequences with the DNA of multiple species whose sequences are not presently available.

Noncoding sequences conserved in a limited number of mammals in the SIM2 interval are frequently functional.

It is demonstrated that sequences conserved in a limited number of mammals are also frequently functional, suggesting that functional conserved noncoding human sequences can be missing in other mammals, even closely related primate species.

Evolutionary Discrimination of Mammalian Conserved Non-Genic Sequences (CNGs)

It is found that CNGs are significantly more conserved than protein-coding genes and noncoding RNAS (ncRNAs) within the mammalian class from primates to monotremes to marsupials.

Covariation in frequencies of substitution, deletion, transposition, and recombination during eutherian evolution.

It was found that all six measures of evolutionary change in the human genome vary significantly in megabase-sized regions genome-wide, and many vary together, indicating that some regions of a genome change slowly by all processes that alter DNA, and others change faster.

Numerous potentially functional but non-genic conserved sequences on human chromosome 21

The integration of the properties of the conserved components of human chromosome 21 to the rapidly accumulating functional data for this chromosome will improve considerably the understanding of the role of sequence conservation in mammalian genomes.

Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons.

Characterization of the largest element in yeast artificial chromosome transgenic mice revealed it to be a coordinate regulator of three genes, interleukin-4,interleuk in-13, and interleucin-5, spread over 120 kilobases.

Comparison of human chromosome 21 conserved nongenic sequences (CNGs) with the mouse and dog genomes shows that their selective constraint is independent of their genic environment.

It is found that CNGs appear to be randomly arranged in intergenic regions, with no bias to be closer or farther from genes, and models for a global role of C NGs in genome function and regulation, through long-distance cis or trans chromosomal interactions are proposed.

Comparative analyses of multi-species sequences from targeted genomic regions

The generation and analysis of over 12 megabases of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region.

Identification and characterization of multi-species conserved sequences.

Two strategies for MCS identification are reported, demonstrating their ability to detect virtually all known actively conserved sequences but very little neutrally evolving sequence (specifically, ancestral repeats).