A genome-wide screen for noncoding elements important in primate evolution - PubMed (original) (raw)

A genome-wide screen for noncoding elements important in primate evolution

Eliot C Bush et al. BMC Evol Biol. 2008.

Abstract

Background: A major goal in the study of human evolution is to identify key genetic changes which occurred over the course of primate evolution. According to one school of thought, many such changes are likely to be found in noncoding sequence. An approach to identifying these involves comparing multiple genomes to identify conserved regions with an accelerated substitution rate in a particular lineage. Such acceleration could be the result of positive selection.

Results: Here we develop a likelihood ratio test method to identify such regions. We apply it not only to the human terminal lineage, as has been done in previous studies, but also to a number of other branches in the primate tree. We present the top scoring elements, and compare our results with previous studies. We also present resequencing data from one particular element accelerated on the human lineage. These data indicate that the element lies in a region of low polymorphism in humans, consistent with the possibility of a recent selective sweep. They also show that the AT to GC bias for polymorphism in this region differs dramatically from that for substitutions.

Conclusion: Our results suggest that screens of this type will be helpful in unraveling the complex set of changes which occurred during primate evolution.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Illustration of methods. A. A phylogeny of the species we used with internal branches labeled. B. An element (green) and repeats (blue) within a 750 kb window. C. Constrained and unconstrained models. For each branch of the phylogeny, the element and the repeats are constrained to be proportional to each other. S is a tree wide scaling factor which accounts for the fact that elements vary in their general level of conservation (i.e. throughout the tree). The unconstrained model is the same as the constrained model, except that for whatever branch we are interested in (here the human terminal branch) we have added another variable F, which allows the element branch to be longer. We calculate the likelihood of the data under these two models. D. The constant of proportionality for each branch is based on the whole genome ratio between element and repeats for a particular branch.

Figure 2

Figure 2

Overlap with previous studies. Venn diagram showing the overlap for human terminal branch elements from this study and two previous studies [6, 7, 39]. The group for the Pollard et al. study has and FDR adjusted p < 0.1, and the group for the Prabhakar study is p < 0.005.

Figure 3

Figure 3

An element on the human terminal branch. Multiple alignment and genomic context for human terminal branch element 2 (HAR2 in Pollard et al. 2006). In the alignment * indicates columns where human is derived.

Figure 4

Figure 4

An element on internal branch 2. Multiple alignment and genomic context for the fourth element on internal branch 2. In the alignment * indicates columns where catarhines are derived.

Similar articles

Cited by

References

    1. King MC, Wilson AC. Evolution at two levels in humans and chimpanzees. Science. 1975;188(4184):107–16. doi: 10.1126/science.1090005. - DOI - PubMed
    1. Rockman MV, Hahn MW, Soranzo N, Zimprich F, Goldstein DB, Wray GA. Ancient and recent positive selection transformed opioid cis-regulation in humans. PLoS Biology. 2005;3(12) - PMC - PubMed
    1. Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Jarvela I. Identification of a variant associated with adult-type hypolactasia. Nat Genet. 2002;30(2):233–237. doi: 10.1038/ng826. - DOI - PubMed
    1. Tishkoff SA, Reed FA, Ranciaro A, Voight BF, Babbitt CC, Silverman JS, Powell K, Mortensen HM, Hirbo JB, Osman M, Ibrahim M, Omar SA, Lema G, Nyambo TB, Ghori J, Bumpstead S, Pritchard JK, Wray GA, Deloukas P. Convergent adaptation of human lactase persistence in Africa and Europe. Nat Genet. 2006;39:31–40. doi: 10.1038/ng1946. - DOI - PMC - PubMed
    1. Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M, Vanderhaeghen P, Haussler D. An RNA gene expressed during cortical development evolved rapidly in humans. Nature. 2006;443(7108):167–172. doi: 10.1038/nature05113. - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources