Changes in Cis-regulatory Elements during Morphological Evolution

Abstract

How have animals evolved new body designs (morphological evolution)? This requires explanations both for simple morphological changes, such as differences in pigmentation and hair patterns between different Drosophila populations and species, and also for more complex changes, such as differences in the forelimbs of mice and bats, and the necks of amphibians and reptiles. The genetic changes and pathways involved in these evolutionary steps require identification. Many, though not all, of these events occur by changes in cis-regulatory (enhancer) elements within developmental genes. Enhancers are modular, each affecting expression in only one or a few tissues. Therefore it is possible to add, remove or alter an enhancer without producing changes in multiple tissues, and thereby avoid widespread (pleiotropic) deleterious effects. Ideally, for a given step in morphological evolution it is necessary to identify (i) the change in phenotype, (ii) the changes in gene expression, (iii) the DNA region, enhancer or otherwise, affected, (iv) the mutation involved, (v) the nature of the transcription or other factors that bind to this site. In practice these data are incomplete for most of the published studies upon morphological evolution. Here, the investigations are categorized according to how far these analyses have proceeded.

Figure 1

Stickleback populations have evolved loss of pelvic fins by loss of a Pitx1 pelvis cis-regulatory element. Pelvic fin-negative populations (b,d) may be restored to an ancestral-like condition (a,c) (Tg1, Tg2) by expression of a Pitx1 transgene that contains 2.5 kilobases of 5′ flanking region taken from a pelvic fin-positive population linked to Pitx1 coding sequence from a pelvic-reduced population. Arrows in a and b show pelvic fin position. In c and d the pelvic apparatus is shown stained with alizarin red. Reprinted with permission from [13], Copyright 2010, AAAS, and D. Kingsley.

Figure 2

Pigmentation in different Ugandan populations of Drosophila melanogaster varies due to mutations in the ebony cis-regulatoryelement. Posterior parts of each abdominal segment are dark due to absence of ebony expression. Segments in the U53 population have higher overall levels of ebony mRNA than in U76 (names indicate the per-cent darkness of the A4 abdominal segment). At least five mutations scattered within a 5′-located regulatory element of ebony decrease ebony expression in the dark population. Reprinted with permission from [24], Copyright 2009, AAAS.

Figure 3

Male-specific pigmentation in Drosophila santomea lost in part by mutations in the tan gene cis-regulatory element. D. santomea and D. yakuba occupy the same island but only D. yakuba retains their shared ancestral condition of intense pigmentation in male abdominal segments A5 and A6. Abdominal cuticles are displayed with the dorsal tergites to the right. Reprinted with permission from [30], Copyright 2008, Elsevier.

Figure 4

Trichome pattern on larvae of Drosophila sechellia lost by mutations in the shavenbaby (svb) gene cis-regulatory element. Confocal micrographs are shown for abdominal segments 1 and 2 of each species. Reprinted with permission from [31], Copyright 2000, National Academy of Sciences, USA, and D. Stern.

Figure 5

Evolution of male-specific wing spot in Drosophila biarmipes involved acquisition of new Engrailed binding motifs in the yellow gene cis-regulatory element which limit expression to the anterior compartment of the wing. Reprinted with permission from [32], Copyright 2005, Macmillan Publishers Ltd.

Figure 6

Male-specific pigmentation in Drosophila melanogaster and D. willistoni differ by ‘molecular remodelling’ of Abd-B and dsx binding motifs within the intron cis-regulatory element of the bric à brac gene, bab1. Reprinted with permission from [26], Copyright 2008, Elsevier.

Figure S1

Retinoic acid response elements (RAREs) in vertebrate Hox gene enhancers. The hexamer repeats are underlined. Yellow highlight, fully conserved bases; red, highly conserved. Sequences, from ENSEMBL or NCBI databases, are aligned using Vector NTI. Lizard is Anole lizard; Armadillo is nine-banded armadillo; Sloth is two-toed sloth.