Transcription Factor‐binding Sites: Recent Evolution in the Human Lineage


Alteration in transcriptional regulatory mechanisms represents an important platform for evolutionary change yet relatively little is known about the extent to which evolution of transcriptional control mechanisms has contributed to recent human evolution. Recent computational analysis suggests that a significant proportion of functional human–chimpanzee sequence differences may affect regulatory elements thus opening up a fruitful avenue for future research to identify pathways underlying recent human evolution and diversity as well as disease predisposition.

Keywords: transcription; binding sites; human evolution; gene regulation

Figure 1.

Repeated morphological evolution through cis‐regulatory changes in the Drosophila yellow gene locus. For each species, the presence or absence of a wing spot is indicated with a solid filled or an empty box, respectively. Species examined in the study by Prud'homme et al. are indicated by an asterisk.

Figure 2.

Mouse chromosome 18 map of candidate transcription factor binding sites conserved between mouse and chimpanzee but lost in human lineage since the last common ancestor with chimpanzees (‘human mutated sites’). Shown is the distribution of candidate TFBSs plotted against mouse chromosome 18 in the UCSC genome browser. The horizontal line indicates a 10‐fold over median threshold. See (Donaldson and Gottgens, ,b) for more details.

Figure 3.

A regulatory SNP causes a human genetic disease by creating a new transcription factor binding site in the α‐globin gene locus. Shown are the first 250 000 bp of human chromosome 16 containing the α‐globin gene locus (using the UCSC genome browser to display gene structure and sequence conservation). In the normal situation, upstream regulatory elements interact with the promoters of the α‐globin genes. The novel GATA site in variant α thalassaemia patients creates a novel promoter like element (De Gobbi et al., ) which sequesters the upstream regulatory element and thus inhibits transcription of the downstream globin genes.



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Further Reading

Bird CP, Stranger BE, Liu M et al. (2007) Fast‐evolving noncoding sequences in the human genome. Genome Biology 8(6): R118.

Lowe CB, Bejerano G and Haussler D (2007) Thousands of human mobile element fragments undergo strong purifying selection near developmental genes. Proceedings of the National Academy of Sciences of the USA 104(19): 8005–8010.

Wray GA (2007) The evolutionary significance of cis‐regulatory mutations. Nature Reviews Genetics 8(3): 206–216.

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How to Cite close
Göttgens, Berthold(Dec 2007) Transcription Factor‐binding Sites: Recent Evolution in the Human Lineage. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020774]