Do novel complex traits evolve when pre-existent complex developmental networks are recruited into new places in the body? Here we look closely at the genomic fingerprints that are produced as a result of gene network co-option.

Human tumors result from an evolutionary process operating on somatic cells within tissues, whereby natural selection operates on the phenotypic variability generated by the accumulation of genetic, genomic and epigenetic alterations. This somatic evolution leads to adaptations such as increased proliferative, angiogenic, and invasive phenotypes. In this review we outline how cancer genomes are beginning to be investigated from an evolutionary perspective. We describe recent progress in the cataloging of somatic genetic and genomic alterations, and investigate the contributions of germline as well as epigenetic factors to cancer genome evolution. Finally, we outline the challenges facing researchers who investigate the processes driving the evolution of the cancer genome.

Positive Darwinian selection on advantageous point substitutions has been demonstrated in many genes. We here provide empirical evidence, for the first time, that positive selection can also act on insertion͞deletion (indel) substitutions in the evolution of a protein. CATSPER1 is a voltage-gated calcium channel found exclusively in the plasma membrane of the mammalian sperm tail and it is essential for sperm motility. We determined the DNA sequences of the first exon of the CATSPER1 gene from 15 primates, which encodes the intracellular N terminus region of Ϸ400 aa. These sequences exhibit an excessively high frequency of indels. However, all indels have lengths that are multiples of 3 nt (3n indels) and do not disrupt the ORF. The number of indel substitutions per site per year in CATSPER1 is five to eight times the corresponding rates calculated from two large-scale primate genomic comparisons, which represent the neutral rate of indel substitutions. Moreover, CATSPER1 indels are considerably longer than neutral indels. These observations strongly suggest that positive selection has been promoting the fixation of indel mutations in CATSPER1 exon 1. It has been shown in certain ion channels that the length of the N terminus region affects the rate of channel inactivation. This finding suggests that the selection detected may be related to the regulation of the CATSPER1 channel, which can affect sperm motility, an important determinant in sperm competition.T here have been dozens of reports on detection of positive Darwinian selection at the DNA sequence level (1-3) since the pioneering work by Hughes and Nei (4) on mammalian MHC genes. The majority of the positively selected genes are involved in host-pathogen interactions (4-8) or reproduction (9-18), although a small number of the genes are of other functions (19,20). In all these cases, positive selection has been shown to promote nonsynonymous (amino acid-replacing) nucleotide substitutions that are presumably advantageous. In theory, certain insertion͞deletion (indel) mutations in protein-coding regions may also be advantageous and subject to positive selection. Naturally occurring polymorphisms of indels that alter protein function have been reported (21). However, there has been no evidence for the operation of positive selection promoting fixations of indel mutations. This is probably because a large proportion of indel substitutions would disrupt the reading frame of a gene and thus be subject to strong purifying selection, which makes it difficult to detect positive selection. Nevertheless, here we provide evidence for the operation of positive selection on indel substitutions in the primate CATSPER1 gene, and demonstrate that positive selection plays a role in the evolutionary change of protein length.CATSPER1 is a voltage-gated calcium ion channel that is exclusively found in the plasma membrane of the principal piece of the sperm tail (22). It is necessary for cAMP-induced Ca 2ϩ influx, normal sperm motility, and penetration of the egg (22). Targe...

Metallothioneins (MTs) are a class of metal-binding proteins characterized by a high cysteine content and low molecular weight. MTs play an important role in metal metabolism and protect cells against the toxic effects of radiation, alkylating agents and oxygen free radicals. The evidence that individual genetic characteristics of MTs play an important role in physiological and pathological processes associated with antioxidant defense and detoxification inspired targeted studies of genetic polymorphisms in a clinical context. In recent years, common MT polymorphisms were identified and associated with, particularly, western lifestyle diseases such as cancer, complications of atherosclerosis, and type 2 diabetes mellitus along with related complications. This review summarizes all evidence regarding MT polymorphisms of major human MTs (MT1, MT2, MT3 and MT4), their relation to pathological processes, and outlines specific applications of MTs as a set of genetic markers for certain pathologies.

In insects, forewings and hindwings usually have different shapes, sizes, and color patterns. A variety of RNAi experiments across insect species have shown that the hox gene Ultrabithorax (Ubx) is necessary to promote hindwing identity. However, it remains unclear whether Ubx is sufficient to confer hindwing fate to forewings across insects. Here, we address this question by over-expressing Ubx in the butterfly Bicyclus anynana using a heat-shock promoter. Ubx whole-body over-expression during embryonic and larvae development led to body plan changes in larvae but to mere quantitative changes to adult morphology, respectively. Embryonic heat-shocks led to fused segments, loss of thoracic and abdominal limbs, and transformation of head limbs to larger appendages. Larval heat-shocks led to reduced eyespot size in the expected homeotic direction, but neither additional eyespots nor wing shape changes were observed in forewings as expected of a homeotic transformation. Interestingly, Ubx was found to be expressed in a novel, non-characteristic domain - in the hindwing eyespot centers. Furthermore, ectopic expression of Ubx on the pupal wing activated the eyespot-associated genes spalt and Distal-less, known to be directly repressed by Ubx in the fly׳s haltere and leg primordia, respectively, and led to the differentiation of black wing scales. These results suggest that Ubx has been co-opted into a novel eyespot gene regulatory network, and that it is capable of activating black pigmentation in butterflies.