Human‐specific Accelerated Evolution of Noncoding Sequences

Matthew T Webster, Uppsala University, Uppsala, Sweden

Published online: May 2008

DOI: 10.1002/9780470015902.a0020849

Mutations in noncoding elements that regulate gene expression are likely to be responsible for a large fraction of phenotypic evolution. Hundreds of putative regulatory elements have been identified with accelerated evolutionary rates in the human lineage, which could be involved in human-specific adaptations. However, instead of being driven by natural selection, the elevated rates of sequence evolution appear to be largely governed by neutral processes.

Keywords: human evolution; noncoding DNA; natural selection; gene regulation; recombination

Figure 1. Phylogenetic tree of the 17 vertebrates used by Pollard et al. (2006a, 2006b) to identify human-accelerated regions (HARs). Initially, alignments of chimpanzee, rat and mouse genome were compared to identify approximately 35 000 conserved elements. Subsequently, these elements were analysed for evidence of increased substitution rate along the human lineage since the human–chimpanzee split (highlighted in grey). For this analysis, the chimpanzee, rat and mouse genomes were excluded because they were used to infer conservation (along with rabbit and macaque that share internal branches between human and the excluded genomes). A total of 49 HARs were identified with a FDR of 5%.
Figure 2. A proposed model of BGC. The two pairs of lines represent both strands of DNA from two parental chromosomes. (a) Consider homologous chromosomes that are heterozygous for an SNP where one allele is G:C and the other is A:T. (b) A double-stranded break (DSB) occurs in one chromosome. (c) A strand from the unbroken chromosome invades the DSB. A G:T base mismatch is created in a region of pairing between strands from both chromosomes. (d) The unbroken DNA is used as a template to synthesize new DNA (dotted lines) to repair the gap. The G:T mismatch is preferentially replaced by a G:C pair by repair enzymes. (e) The DNA molecules are cut and the Holliday junctions are resolved as either crossing over or a gene conversion event. Both alleles of the SNP are now G:C. This process therefore leads to a bias in transmission of G:C alleles. In addition to this process, DSBs have been observed to preferentially occur at A:T alleles at one hotspot (Jeffreys and Neumann, 2002), which also results in a bias in favour of GC.
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Related Sub-Topics:

Molecular Evolution | Human Evolution | Evolution Rates
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Article Title: Human‐specific Accelerated Evolution of Noncoding Sequences
 
How to Cite close
Webster, Matthew T(May 2008) Human‐specific Accelerated Evolution of Noncoding Sequences. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020849]