Most great ape genetic variation remains uncharacterized; however, its study is critical for understanding population history, recombination, selection and susceptibility to disease. Here we sequence to high coverage a total of 79 wild- and captive-born individuals representing all six great ape species and seven subspecies and report 88.8 million single nucleotide polymorphisms. Our analysis provides support for genetically distinct populations within each species, signals of gene flow, and the split of common chimpanzees into two distinct groups: Nigeria-Cameroon/western and central/eastern populations. We find extensive inbreeding in almost all wild populations, with eastern gorillas being the most extreme. Inferred effective population sizes have varied radically over time in different lineages and this appears to have a profound effect on the genetic diversity at, or close to, genes in almost all species. We discover and assign 1,982 loss-of-function variants throughout the human and great ape lineages, determining that the rate of gene loss has not been different in the human branch compared to other internal branches in the great ape phylogeny. This comprehensive catalogue of great ape genome diversity provides a framework for understanding evolution and a resource for more effective management of wild and captive great ape populations.

/pdf/great-ape-genetic-diversity-and-population-history-4rzraosn9b.pdf

Great ape genetic diversity and population history

This protocol describes how to annotate genomic variants using either the ANNOVAR software or the web-based wANNOVAR tool. Recent developments in sequencing techniques have enabled rapid and high-throughput generation of sequence data, democratizing the ability to compile information on large amounts of genetic variations in individual laboratories. However, there is a growing gap between the generation of raw sequencing data and the extraction of meaningful biological information. Here, we describe a protocol to use the ANNOVAR (ANNOtate VARiation) software to facilitate fast and easy variant annotations, including gene-based, region-based and filter-based annotations on a variant call format (VCF) file generated from human genomes. We further describe a protocol for gene-based annotation of a newly sequenced nonhuman species. Finally, we describe how to use a user-friendly and easily accessible web server called wANNOVAR to prioritize candidate genes for a Mendelian disease. The variant annotation protocols take 5–30 min of computer time, depending on the size of the variant file, and 5–10 min of hands-on time. In summary, through the command-line tool and the web server, these protocols provide a convenient means to analyze genetic variants generated in humans and other species.

/pdf/genomic-variant-annotation-and-prioritization-with-annovar-4t4y88v5eo.pdf

Genomic variant annotation and prioritization with ANNOVAR and wANNOVAR

The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three per cent of its ancestral genes survived. We reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes. Our findings indicate that survival was nonrandom, and in two cases, convergent across placental and marsupial mammals. We conclude that the gene content of the Y chromosome became specialized through selection to maintain the ancestral dosage of homologous X–Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability. We propose that beyond its roles in testis determination and spermatogenesis, the Y chromosome is essential for male viability, and has unappreciated roles in Turner’s syndrome and in phenotypic differences between the sexes in health and disease.

Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators

Meiotic drivers are genetic variants that selfishly manipulate the production of gametes to increase their own rate of transmission, often to the detriment of the rest of the genome and the individual that carries them. This genomic conflict potentially occurs whenever a diploid organism produces a haploid stage, and can have profound evolutionary impacts on gametogenesis, fertility, individual behaviour, mating system, population survival, and reproductive isolation. Multiple research teams are developing artificial drive systems for pest control, utilising the transmission advantage of drive to alter or exterminate target species. Here, we review current knowledge of how natural drive systems function, how drivers spread through natural populations, and the factors that limit their invasion.

/pdf/the-ecology-and-evolutionary-dynamics-of-meiotic-drive-1ggvfl1equ.pdf

The Ecology and Evolutionary Dynamics of Meiotic Drive

The association of chromosome rearrangements with speciation is well established, and there is a long history of theory and evidence relating to “chromosomal speciation”. Genomic sequencing has the potential to provide new insights into how reorganization of genome structure promotes divergence, and in model systems has demonstrated reduced gene flow in rearranged segments. However, there are limits to what we can understand from a small number of model systems, which each only tell us about one episode of chromosomal speciation. Progressing from patterns of association between chromosome (and genic) change, to understanding processes of speciation requires both comparative studies across diverse systems and integration of genome-scale sequence comparisons with other lines of evidence. Here we showcase a promising example of chromosomal speciation in a non-model organism, the endemic Australian marsupial genus Petrogale. We present initial phylogenetic results from exon-capture that resolve a history of divergence associated with extensive and repeated chromosome rearrangements. Yet it remains challenging to disentangle gene tree heterogeneity caused by recent divergence and gene flow in this and other such recent radiations. We outline a way forward for better integration of comparative genomic sequence data with evidence from molecular cytogenetics, and analyses of shifts in the recombination landscape and potential disruption of meiotic segregation and epigenetic programming. In all likelihood, chromosome rearrangements impact multiple cellular processes and these effects need to be considered together, along with those of genic divergence. Understanding the effects of chromosome rearrangements together with genic divergence will require development of more integrative theory and inference methods. Together, new data and analysis tools will combine to shed light on long standing questions of how chromosome and genic divergence promote speciation.

/pdf/chromosomal-speciation-in-the-genomics-era-disentangling-4eepbopekk.pdf

Chromosomal Speciation in the Genomics Era: Disentangling Phylogenetic Evolution of Rock-wallabies

The unique inheritance pattern of the X chromosome exposes it to natural selection in a way that is different from that of the autosomes, potentially resulting in accelerated evolution. We perform a comparative analysis of X chromosome polymorphism in 10 great ape species, including humans. In most species, we identify striking megabase-wide regions, where nucleotide diversity is less than 20% of the chromosomal average. Such regions are found exclusively on the X chromosome. The regions overlap partially among species, suggesting that the underlying targets are partly shared among species. The regions have higher proportions of singleton SNPs, higher levels of population differentiation, and a higher nonsynonymous-to-synonymous substitution ratio than the rest of the X chromosome. We show that the extent to which diversity is reduced is incompatible with direct selection or the action of background selection and soft selective sweeps alone, and therefore, we suggest that very strong selective sweeps have independently targeted these specific regions in several species. The only genomic feature that we can identify as strongly associated with loss of diversity is the location of testis-expressed ampliconic genes, which also have reduced diversity around them. We hypothesize that these genes may be responsible for selective sweeps in the form of meiotic drive caused by an intragenomic conflict in male meiosis.

https://www.pnas.org/content/pnas/112/20/6413.full.pdf

Extreme selective sweeps independently targeted the X chromosomes of the great apes

The unique inheritance pattern of X chromosomes makes them preferential targets of adaptive evolution We here investigate natural selection on the X chromosome in all species of great apes We find that diversity is more strongly reduced around genes on the X compared with autosomes, and that a higher proportion of substitutions results from positive selection Strikingly, the X exhibits several megabase long regions where diversity is reduced more than five fold These regions overlap significantly among species, and have a higher singleton proportion, population differentiation, and nonsynonymous to synonymous substitution ratio We rule out background selection and soft selective sweeps as explanations for these observations, and conclude that several strong selective sweeps have occurred independently in similar regions in several species Since these regions are strongly associated with ampliconic sequences we propose that intra-genomic conflict between the X and the Y chromosomes is a major driver of X chromosome evolution

/pdf/strong-selective-sweeps-associated-with-ampliconic-regions-13lqg8y4ha.pdf

Great Ape Genome Diversity Project

Papers

Extreme selective sweeps independently targeted the X chromosomes of the great apes

Strong selective sweeps associated with ampliconic regions in great ape X chromosomes