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Noncoding sequences near duplicated genes evolve rapidly.

ABSTRACT: Gene expression divergence and chromosomal rearrangements have been put forward as major contributors to phenotypic differences between closely related species. It has also been established that duplicated genes show enhanced rates of positive selection in their amino acid sequences. If functional divergence is largely due to changes in gene expression, it follows that regulatory sequences in duplicated loci should also evolve rapidly. To investigate this hypothesis, we performed likelihood ratio tests (LRTs) on all noncoding loci within 5 kb of every transcript in the human genome and identified sequences with increased substitution rates in the human lineage since divergence from Old World Monkeys. The fraction of rapidly evolving loci is significantly higher nearby genes that duplicated in the common ancestor of humans and chimps compared with nonduplicated genes. We also conducted a genome-wide scan for nucleotide substitutions predicted to affect transcription factor binding. Rates of binding site divergence are elevated in noncoding sequences of duplicated loci with accelerated substitution rates. Many of the genes associated with these fast-evolving genomic elements belong to functional categories identified in previous studies of positive selection on amino acid sequences. In addition, we find enrichment for accelerated evolution nearby genes involved in establishment and maintenance of pregnancy, processes that differ significantly between humans and monkeys. Our findings support the hypothesis that adaptive evolution of the regulation of duplicated genes has played a significant role in human evolution.

SUBMITTER: Kostka D

PROVIDER: S-EPMC2942038 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Noncoding sequences near duplicated genes evolve rapidly.

Kostka Dennis D Hahn Matthew W MW Pollard Katherine S KS

Genome biology and evolution 20100629

Gene expression divergence and chromosomal rearrangements have been put forward as major contributors to phenotypic differences between closely related species. It has also been established that duplicated genes show enhanced rates of positive selection in their amino acid sequences. If functional divergence is largely due to changes in gene expression, it follows that regulatory sequences in duplicated loci should also evolve rapidly. To investigate this hypothesis, we performed likelihood rati ...[more]

PMID: 20660939

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Project description:Here we focus on identifying conserved elements that are required for Chaserr function, a lncRNA that we recently characterized as being essential for mouse viability (https://doi.org/10.1038/s41467-019-13075-8). Chaserr is highly conserved in different species, and is located in close proximity (<2kb) to the transcription start site of CHD2. It acts in concert with the CHD2 protein to maintain proper Chd2 expression levels. Using the LncLOOM framework we identified AUGG enriched conserved elements which are located in the last exon of mouse Chaserr. In order to identify proteins that potentially bind to these conserved regions, we used in vitro transcription to generate the following biotinylated RNAs; along with their antisense controls: 1) The WT sequence, containing the first 322 nt of the last exon of Chaserr (bases 764–1086 of the NR_037601 isoform). An antisense control fragment was also prepared, labelled as AWT 2) The mutant conserved (MC) sequence, that contained AUGG→UACC mutations in four conserved motifs that were found using LncLOOM. An antisense control fragment was also prepared, labelled as AMC 3) The muatant all (MA) sequence in which all seven of the AUGG sites in the last exon were mutated to UACC. An antisense control fragment was also prepared, labelled as AMA 4) We also included a No Probe Control, which did not contain an RNA fragment. The fragments were incubated with N2a cell lysates followed by RNA-pulldown and Mass Spec analysis. The experiment was performed in triplicate. A total of 938 proteins were found to associate with the WT sequence: 74 of these were enriched ≥3-fold compared to the antisense sequence.We identified 9 proteins that had ≥2-fold higher recovery when using the WT sequence compared to both mutants. Included in these proteins was DHX36, which showed the highest enrichment compared to the mutated sequences. We validated the association of DHX36 with Chaserr through RNA immunoprecipitation experiments.

Dataset Information

Noncoding sequences near duplicated genes evolve rapidly.

Publications

Noncoding sequences near duplicated genes evolve rapidly.

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