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Positive selection of a gene family during the emergence of humans and African apes

Abstract

Gene duplication followed by adaptive evolution is one of the primary forces for the emergence of new gene function1. Here we describe the recent proliferation, transposition and selection of a 20-kilobase (kb) duplicated segment throughout 15 Mb of the short arm of human chromosome 16. The dispersal of this segment was accompanied by considerable variation in chromosomal-map location and copy number among hominoid species. In humans, we identified a gene family (morpheus) within the duplicated segment. Comparison of putative protein-encoding exons revealed the most extreme case of positive selection among hominoids. The major episode of enhanced amino-acid replacement occurred after the separation of human and great-ape lineages from the orangutan. Positive selection continued to alter amino-acid composition after the divergence of human and chimpanzee lineages. The rapidity and bias for amino-acid-altering nucleotide changes suggest adaptive evolution of the morpheus gene family during the emergence of humans and African apes. Moreover, some genes emerge and evolve very rapidly, generating copies that bear little similarity to their ancestral precursors. Consequently, a small fraction of human genes may not possess discernible orthologues within the genomes of model organisms.

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Figure 1: Sequence properties of the LCR16a duplication.
Figure 2: Comparative FISH analysis among primates.
Figure 3: Phylogeny of coding and non-coding portions of the LCR16a duplication.

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Acknowledgements

We thank W. E. Kutz and D. Zivkovic for technical assistance and sequencing analyses. This work was supported by grants from the National Institutes of Health and the US Department of Energy to E.E.E., and grants from Progretti di Interesse Nationale (PRIN), Centro Eccelenza (CE), Ministero per la Ricerca Scientifica e Tecnologica (MURST) and Telethon to M.R. We are grateful to C. I. Wu, A. Chakravarti, D. Cutler, D. Locke, G. Matera and H. Willard for comments on this manuscript.

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Correspondence to Evan E. Eichler.

Supplementary information

Supplement Figs. 1 to 6 with legends (DOC 201 kb)

Supplement Fig. 7

Multiple sequence alignment of exon 2 and flanking intronic sequences. (PDF 7 kb)

Supplement Fig. 8

Multiple sequence alignment of exon 4 and flanking intronic sequences. (PDF 6 kb)

Table 1 (XLS 24 kb)

Table 2 (XLS 17 kb)

Table 3 (XLS 16 kb)

Table 4 (XLS 22 kb)

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Johnson, M., Viggiano, L., Bailey, J. et al. Positive selection of a gene family during the emergence of humans and African apes. Nature 413, 514–519 (2001). https://doi.org/10.1038/35097067

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