Inferring selective constraint from population genomic data suggests recent regulatory turnover in the human brain

Daniel R. Schrider, Andrew D. Kern

Research output: Contribution to journalArticle

10 Scopus citations


The comparative genomics revolution of the past decade has enabled the discovery of functional elements in the human genomevia sequence comparison. While that is so, an important class of elements, those specific to humans, is entirelymissed by searching for sequence conservation across species. Here we present an analysis based on variation data among human genomes that utilizes a supervised machine learning approach for the identification of human-specific purifying selection in the genome. Using only allele frequency information from the complete low-coverage 1000 Genomes Project data set in conjunction with a support vector machine trained from known functional and nonfunctional portions of the genome, we are able to accurately identify portions of the genome constrained by purifying selection. Our method identifies previously known human-specific gains or losses of function and uncovers many novel candidates. Candidate targets for gain and loss of function along the human lineage include numerous putative regulatory regions of genes essential for normal development of the central nervous system, including a significant enrichment of gain of function events near neurotransmitter receptor genes. These results are consistent with regulatory turnover being a key mechanism in the evolution of human-specific characteristics of brain development. Finally, we show that the majority of the genome is unconstrained by natural selection currently, in agreement with what has been estimated from phylogenetic methods but in sharp contrast to estimates based on transcriptomics or other high-throughput functional methods.

Original languageEnglish (US)
Pages (from-to)3511-3528
Number of pages18
JournalGenome biology and evolution
Issue number12
StatePublished - Jan 1 2015

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Genetics


  • Human evolution
  • Natural selection
  • Population genetics

Fingerprint Dive into the research topics of 'Inferring selective constraint from population genomic data suggests recent regulatory turnover in the human brain'. Together they form a unique fingerprint.

  • Cite this