An evolutionary approach reveals a high protein-coding capacity of the human genome

Nekrutenko, Anton; Chung, Wen Yu; Li, Wen-Hsiung

doi:10.1016/s0168-9525(03)00114-8

Cited by 32 publications

(25 citation statements)

References 19 publications

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“…Recently, a large proportion of novel noncoding mouse transcripts (Okazaki et al 2002) and nongenic conserved blocks between mouse and human (Dermitzakis et al 2002) have been identified supporting these conclusions. Nevertheless, Nekrutenko et al (2003) identified a large population (14,000) of potential protein-coding exons using an evolutionary comparative genomics approach between mouse and human, with 111 of those on Chromosome 22, and found 89 (∼80%) are expressed in our transcription data (Nekrutenko et al 2003). Additional evolutionary sequence comparisons of the expressed transfrag regions to the genomes of species closer to human are in progress and may indicate a greater degree of conservation.…”

Section: Transcriptome Of Chromosomes 21 and 22mentioning

confidence: 81%

“…Although 30,000 to 40,000 is presently the most favorable estimate, emerging data based on a variety of computational and experimental approaches indicate that these estimates need to be re-evaluated (Chen et al 2002;Okazaki et al 2002;Saha et al 2002;Guigo et al 2003;Nekrutenko et al 2003;Rinn et al 2003). We recently reported the results of an unbiased analysis of human Chromosomes 21 and 22 that systematically interrogated the entire nonrepetitive regions of these chromosomes for the location of transcription using high-density oligonucleotide arrays (Fodor et al 1991(Fodor et al , 1993Pease et al 1994;Kapranov et al 2002).…”

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confidence: 99%

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Novel RNAs Identified From an In-Depth Analysis of the Transcriptome of Human Chromosomes 21 and 22

Kampa¹,

Cheng²,

Kapranov³

et al. 2004

Genome Res.

474

377

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In this report, we have achieved a richer view of the transcriptome for Chromosomes 21 and 22 by using high-density oligonucleotide arrays on cytosolic poly(A) + RNA. Conservatively, only 31.4% of the observed transcribed nucleotides correspond to well-annotated genes, whereas an additional 4.8% and 14.7% correspond to mRNAs and ESTs, respectively. Approximately 85% of the known exons were detected, and up to 21% of known genes have only a single isoform based on exon-skipping alternative expression. Overall, the expression of the well-characterized exons falls predominately into two categories, uniquely or ubiquitously expressed with an identifiable proportion of antisense transcripts. The remaining observed transcription (49.0%) was outside of any known annotation. These novel transcripts appear to be more cell-line-specific and have lower and less variation in expression than the well-characterized genes. Novel transcripts were further characterized based on their distance to annotations, transcript size, coding capacity, and identification as antisense to intronic sequences. By RT-PCR, 126 novel transcripts were independently verified, resulting in a 65% verification rate. These observations strongly support the argument for a re-evaluation of the total number of human genes and an alternative term for "gene" to encompass these growing, novel classes of RNA transcripts in the human genome.

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Section: Transcriptome Of Chromosomes 21 and 22mentioning

confidence: 81%

mentioning

confidence: 99%

Novel RNAs Identified From an In-Depth Analysis of the Transcriptome of Human Chromosomes 21 and 22

Kampa¹,

Cheng²,

Kapranov³

et al. 2004

Genome Res.

474

377

View full text Add to dashboard Cite

show abstract

“…The weak conservation of transcription factor-binding sites and regulatory networks in mammalian genomes would actually fit with the fact that TE sequence and distribution are highly diverse among species. As a global illustration of the effect of TEs on genic composition and regulation, it was estimated that TE-derived sequences are found in the coding region of 4% of human genes, and are contained in 25% of human promoters (Nekrutenko et al, 2003;van de Lagemaat et al, 2003). TE activity can also indirectly generate beneficial novelties, by hijacking cellular mRNAs and catalyzing the insertion of their complementary DNA in new genomic environments.…”

Section: Good Tes Bad Tesmentioning

confidence: 99%

Transposable elements in the mammalian germline: a comfortable niche or a deadly trap?

2010

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Retrotransposable elements comprise around 50% of the mammalian genome. Their activity represents a constant threat to the host and has prompted the development of adaptive control mechanisms to protect genome architecture and function. To ensure their propagation, retrotransposons have to mobilize in cells destined for the next generation. Accordingly, these elements are particularly well suited to transcriptional networks associated with pluripotent and germinal states in mammals. The relaxation of epigenetic control that occurs in the early developing germline constitutes a dangerous window in which retrotransposons can escape from host restraint and massively expand. What could be observed as risky behavior may turn out to be an insidious strategy developed by germ cells to sense retrotransposons and hold them back in check. Herein, we review recent insights that have provided a detailed picture of the defense mechanisms that concur toward retrotransposon silencing in mammalian genomes, and in particular in the germline. In this lineage, retrotransposons are hit at multiple stages of their life cycle, through transcriptional repression, RNA degradation and translational control. An organized cross-talk between PIWIinteracting small RNAs (piRNAs) and various nuclear and cytoplasmic accessories provides this potent and multilayered response to retrotransposon unleashing in early germ cells.

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“…In any event, 99 % of mouse genes have a human homolog and 96 % are true orthologs as they occur on corresponding chromosome loci. Consequently, at most 1200 (4 %), but possibly as little as 300 (1 %), of human genes have arisen de novo since the rodent and primate lineages split from a com-1 Other studies claim, that perhaps as much as half of the 65,000-75,000 transcriptional units had been previously missed (Wright et al, 2001;Nekrutenko et al, 2003;Rinn et al, 2003), or that the genome contains at least 42,000 genes (Hogenesch et al, 2001). Other estimates, however, suggest that the gene number is less than 25,000 (Pennisi, 2003).…”

confidence: 99%

Echoes from the past – are we still in an RNP world?

Brosius¹

2005

Cytogenet Genome Res

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Availability of the human genome sequence and those of other species is unmeasured in their value for a comprehensive understanding of the architecture, function and evolution of genomes and cells. Various mechanisms keep genomes in flux and generate intra- and interspecies variation. The conversion of RNA modules into DNA and their more or less random integration into chromosomes (retroposition) is in many lineages including our own the most pervasive and perhaps the most enigmatic. The proclivity of such events in extant multicellular eukaryotes, even in more recent evolutionary times, gives the impression that the transition period from the RNP (ribonucleoprotein) world to the emergence of modern cells, where DNA became the predominant carrier of genetic information, has lasted billions of years and is an endlessly drawn-out process rather than the punctuated event one might expect. Apart from the impact of such RNA-mediated processes as retroposition, the role of RNA in a wide variety of cellular functions has only recently become more widely appreciated.

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An evolutionary approach reveals a high protein-coding capacity of the human genome

Cited by 32 publications

References 19 publications

Novel RNAs Identified From an In-Depth Analysis of the Transcriptome of Human Chromosomes 21 and 22

Novel RNAs Identified From an In-Depth Analysis of the Transcriptome of Human Chromosomes 21 and 22

Transposable elements in the mammalian germline: a comfortable niche or a deadly trap?

Echoes from the past – are we still in an RNP world?

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