Constraints and plasticity in genome and molecular-phenome evolution

Koonin, Eugene V.; Wolf, Yuri I.

doi:10.1038/nrg2810

Cited by 147 publications

(125 citation statements)

References 157 publications

(198 reference statements)

Supporting

Mentioning

117

Contrasting

Unclassified

Order By: Relevance

“…Ultimately, the true test for function lies in the detailed, mechanistic dissection of the genetic pathways and cellular activities for each individual putative lncRNA (see Figure 4). We must also keep in mind that the genome may not be a streamlined, highly sculpted space honed by natural selection; it could instead be quite noisy, even wasteful, where genomic junk and evolutionary relics accumulate but may yet adopt useful functions eventually (Lynch 2007;Koonin and Wolf 2010). Thus, at present, it may be best to avoid blanket statements about structure, function, and mechanism, as indeed we have barely begun to scratch the surface of the lncRNA world.…”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNAs: Past, Present, and Future

2013

View full text Add to dashboard Cite

Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years as a potentially new and crucial layer of biological regulation. lncRNAs of all kinds have been implicated in a range of developmental processes and diseases, but knowledge of the mechanisms by which they act is still surprisingly limited, and claims that almost the entirety of the mammalian genome is transcribed into functional noncoding transcripts remain controversial. At the same time, a small number of well-studied lncRNAs have given us important clues about the biology of these molecules, and a few key functional and mechanistic themes have begun to emerge, although the robustness of these models and classification schemes remains to be seen. Here, we review the current state of knowledge of the lncRNA field, discussing what is known about the genomic contexts, biological functions, and mechanisms of action of lncRNAs. We also reflect on how the recent interest in lncRNAs is deeply rooted in biology's longstanding concern with the evolution and function of genomes.T HE past several years have witnessed a steep rise of interest in the study of lncRNAs. Almost on a weekly basis, it seems that a new lncRNA is found to be up-or downregulated in a particular disease, or a new class of noncoding transcripts is uncovered by a transcriptomic study, or a new article heralds a paradigm shift that lncRNAs will bring to our understanding of biology. Without a doubt, the advent of sensitive, high-throughput genomic technologies such as microarrays and next-generation sequencing (NGS) has resulted in an unprecedented ability to detect novel transcripts, the vast majority of which seem not to be derived from annotated protein-coding genes. Despite this explosion of data, however, surprisingly little is known about how lncRNAs function, how many different types of lncRNAs exist, or even whether most of them carry biological significance.In this review, we focus on recently discovered lncRNAs of .200 nt, place these new discoveries in historical context, and outline areas where additional work is needed. The review does not cover "classic" ncRNAs such as ribosomal (r) RNAs, ribozymes, transfer (t)RNAs, small nuclear (sn)RNAs, small nucleolar (sno)RNAs, and telomere-associated RNAs (TERC, TERRA); nor does it cover small ncRNAs such as microRNAs (miRNAs), endogenous small interfering (endo-si)RNAs that participate in RNA interference (RNAi), and Piwi-associated (pi)RNAs. We refer readers to the many

show abstract

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNAs: Past, Present, and Future

2013

View full text Add to dashboard Cite

show abstract

“…Both phenomena are widespread (Lynch and Conery 2000;Wang et al 2008), and both provide an increased diversity of protein sequence, structure, and function (Graveley 2001;Chothia et al 2003;Koonin and Wolf 2010). A negative correlation between these two processes has been reported: Genes belonging to large families were found to have fewer alternative splice forms than singletons or genes belonging to small families (Kopelman et al 2005;Su et al 2006;Talavera et al 2007).…”

mentioning

confidence: 99%

Age-dependent gain of alternative splice forms and biased duplication explain the relation between splicing and duplication

Roux

Robinson‐Rechavi

2010

Genome Res.

View full text Add to dashboard Cite

We analyze here the relation between alternative splicing and gene duplication in light of recent genomic data, with a focus on the human genome. We show that the previously reported negative correlation between level of alternative splicing and family size no longer holds true. We clarify this pattern and show that it is sufficiently explained by two factors. First, genes progressively gain new splice variants with time. The gain is consistent with a selectively relaxed regime, until purifying selection slows it down as aging genes accumulate a large number of variants. Second, we show that duplication does not lead to a loss of splice forms, but rather that genes with low levels of alternative splicing tend to duplicate more frequently. This leads us to reconsider the role of alternative splicing in duplicate retention.

show abstract

“…The evolutionary and functional implications of high-order eukaryotic genome structures remain topics of contention, and have inspired some of the most ambitious evolutionary hypotheses of the genetic and genomic eras (e.g., Doolittle 1978;Lynch 2007;Koonin and Wolf 2010). Largely absent from these debates has been the question of the local ordering of genes themselves within a genome, generally reflecting the common assumption that gene position within the genome is mostly a secondary concern and/or is usually not constrained (Koonin and Wolf 2010).…”

mentioning

confidence: 99%

“…Largely absent from these debates has been the question of the local ordering of genes themselves within a genome, generally reflecting the common assumption that gene position within the genome is mostly a secondary concern and/or is usually not constrained (Koonin and Wolf 2010).…”

mentioning

confidence: 99%

Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints

et al. 2012

View full text Add to dashboard Cite

The order of genes in eukaryotic genomes has generally been assumed to be neutral, since gene order is largely scrambled over evolutionary time. Only a handful of exceptional examples are known, typically involving deeply conserved clusters of tandemly duplicated genes (e.g., Hox genes and histones). Here we report the first systematic survey of microsynteny conservation across metazoans, utilizing 17 genome sequences. We identified nearly 600 pairs of unrelated genes that have remained tightly physically linked in diverse lineages across over 600 million years of evolution. Integrating sequence conservation, gene expression data, gene function, epigenetic marks, and other genomic features, we provide extensive evidence that many conserved ancient linkages involve (1) the coordinated transcription of neighboring genes, or (2) genomic regulatory blocks (GRBs) in which transcriptional enhancers controlling developmental genes are contained within nearby bystander genes. In addition, we generated ChIP-seq data for key histone modifications in zebrafish embryos, which provided further evidence of putative GRBs in embryonic development. Finally, using chromosome conformation capture (3C) assays and stable transgenic experiments, we demonstrate that enhancers within bystander genes drive the expression of genes such as Otx and Islet, critical regulators of central nervous system development across bilaterians. These results suggest that ancient genomic functional associations are far more common than previously thought-involving~12% of the ancestral bilaterian genome-and that cis-regulatory constraints are crucial in determining metazoan genome architecture.

show abstract

Constraints and plasticity in genome and molecular-phenome evolution

Cited by 147 publications

References 157 publications

Long Noncoding RNAs: Past, Present, and Future

Long Noncoding RNAs: Past, Present, and Future

Age-dependent gain of alternative splice forms and biased duplication explain the relation between splicing and duplication

Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints

Contact Info

Product

Resources

About