Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

Three strikingly different alternative male mating morphs (aggressive 'independents', semicooperative 'satellites' and female-mimic 'faeders') coexist as a balanced polymorphism in the ruff, Philomachus pugnax, a lek-breeding wading bird. Major differences in body size, ornamentation, and aggressive and mating behaviors are inherited as an autosomal polymorphism. We show that development into satellites and faeders is determined by a supergene consisting of divergent alternative, dominant and non-recombining haplotypes of an inversion on chromosome 11, which contains 125 predicted genes. Independents are homozygous for the ancestral sequence. One breakpoint of the inversion disrupts the essential CENP-N gene (encoding centromere protein N), and pedigree analysis confirms the lethality of homozygosity for the inversion. We describe new differences in behavior, testis size and steroid metabolism among morphs and identify polymorphic genes within the inversion that are likely to contribute to the differences among morphs in reproductive traits.

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A supergene determines highly divergent male reproductive morphs in the ruff

As populations diverge, genetic differences accumulate across the genome. Spurred by rapid developments in sequencing technology, genome-wide population surveys of natural populations promise insights into the evolutionary processes and the genetic basis underlying speciation. Although genomic regions of elevated differentiation are the focus of searches for 'speciation genes', there is an increasing realization that such genomic signatures can also arise by alternative processes that are not related to population divergence, such as linked selection. In this Review, we explore methodological trends in speciation genomic studies, highlight the difficulty in separating processes related to speciation from those emerging from genome-wide properties that are not related to reproductive isolation, and provide a set of suggestions for future work in this area.

Making sense of genomic islands of differentiation in light of speciation.

Chromosomal inversions have long fascinated evolutionary biologists due to their suppression of recombination, which can protect co-adapted alleles. Emerging research documents that inversions are commonly linked to spectacular phenotypes and have a pervasive role in eco-evolutionary processes, from mating systems, social organisation, environmental adaptation, and reproductive isolation to speciation. Studies also reveal that inversions are taxonomically widespread, with many being old and large, and that balancing selection is commonly facilitating their maintenance. This challenges the traditional view that the role of balancing selection in maintaining variation is relatively minor. The ubiquitous importance of inversions in ecological and evolutionary processes suggests that structural variation should be better acknowledged and integrated in studies pertaining to the molecular basis of adaptation and speciation.

Eco-Evolutionary Genomics of Chromosomal Inversions.

Sex chromosomes can evolve once recombination is halted between a homologous pair of chromosomes. Owing to detailed studies using key model systems, we have a nuanced understanding and a rich review literature of what happens to sex chromosomes once recombination is arrested. However, three broad questions remain unanswered. First, why do sex chromosomes stop recombining in the first place? Second, how is recombination halted? Finally, why does the spread of recombination suppression, and therefore the rate of sex chromosome divergence, vary so substantially across clades? In this review, we consider each of these three questions in turn to address fundamental questions in the field, summarize our current understanding, and highlight important areas for future work.

How to make a sex chromosome.

Leif Andersson and colleagues report the genome sequence of the ruff, a bird species with three male morphs with different reproductive strategies. Satellite and faeder morphs differ from the common independent morph by a 4.5-Mb inversion that occurred approximately 3.8 million years ago, and multiple genetic changes within this inverted region are associated with the satellite and faeder morphs. The ruff is a Palearctic wader with a spectacular lekking behavior where highly ornamented males compete for females1,2,3,4. This bird has one of the most remarkable mating systems in the animal kingdom, comprising three different male morphs (independents, satellites and faeders) that differ in behavior, plumage color and body size. Remarkably, the satellite and faeder morphs are controlled by dominant alleles5,6. Here we have used whole-genome sequencing and resolved the enigma of how such complex phenotypic differences can have a simple genetic basis. The Satellite and Faeder alleles are both associated with a 4.5-Mb inversion that occurred about 3.8 million years ago. We propose an evolutionary scenario where the Satellite chromosome arose by a rare recombination event about 500,000 years ago. The ruff mating system is the result of an evolutionary process in which multiple genetic changes contributing to phenotypic differences between morphs have accumulated within the inverted region.

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Structural genomic changes underlie alternative reproductive strategies in the ruff (Philomachus pugnax)

Sex-linked barring is a fascinating plumage pattern in chickens recently shown to be associated with two non-coding and two missense mutations affecting the ARF transcript at the CDKN2A tumor suppressor locus. It however remained a mystery whether all four mutations are indeed causative and how they contribute to the barring phenotype. Here, we show that Sex-linked barring is genetically heterogeneous, and that the mutations form three functionally different variant alleles. The B0 allele carries only the two non-coding changes and is associated with the most dilute barring pattern, whereas the B1 and B2 alleles carry both the two non-coding changes and one each of the two missense mutations causing the Sex-linked barring and Sex-linked dilution phenotypes, respectively. The data are consistent with evolution of alleles where the non-coding changes occurred first followed by the two missense mutations that resulted in a phenotype more appealing to humans. We show that one or both of the non-coding changes are cis-regulatory mutations causing a higher CDKN2A expression, whereas the missense mutations reduce the ability of ARF to interact with MDM2. Caspase assays for all genotypes revealed no apoptotic events and our results are consistent with a recent study indicating that the loss of melanocyte progenitors in Sex-linked barring in chicken is caused by premature differentiation and not apoptosis. Our results show that CDKN2A is a major locus driving the differentiation of avian melanocytes in a temporal and spatial manner.

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Doreen Schwochow Thalmann

Papers

Structural genomic changes underlie alternative reproductive strategies in the ruff (Philomachus pugnax)

The evolution of Sex-linked barring alleles in chickens involves both regulatory and coding changes in CDKN2A.