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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]

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