Genomics – Tutorial Genomics, Ecology, Evolution, etc

Introduction Environmental pollution is a widespread problem that living organisms have to contend with on a global scale. In contaminated sites especially, wild populations undergo intense selective pressure that may result in phenotypic adaptations to pollutants (Hendry et al., 2008). The scientific article (Reid et al., 2016) discussed in this blogpost explores the genetic mechanisms that have allowed the rapid adaptation to industrial pollutants in wild Atlantic killifish populations. Results The genomic landscape of the killifish populations Atlantic killifish (Fundulus heteroclitus) are non-migratory fish that are abundant along the US east coastline (Fig. 1A). Some killifish populations show inherited resistance to lethal levels of industrial pollutants in sites that have been contaminated for decades. For instance, the authors show that the percentage of larva that survive in increasing concentrations of a highly toxic pollutant called PCB 126, is higher in tolerant populations compared to the sensitive populations (Fig. 1B). To understand the genetic adaptations underlying the rapid adaptation to polluted sites in killifish populations, the authors sequenced the complete genomes from eight populations. Four tolerant populations that reside in highly polluted sites were sampled. Each one was paired with a sensitive population from a nearby site (Fig. 1A). The authors combined …

Adaptation / Conservation / Evolution / Genomics

The parallel evolution in amniotes seen through the eye of functional nodal mutations

December 1, 2017November 8, 2021

Introduction In this article the authors describe an evolutionary convergence in mammals, birds, and reptiles, based on genomic data from NCBI. The evolution of different species and lineages is due to mutations that can appear and accumulate in organisms over time. Those mutations need a high functional potential and have to be conserved in time in order to form new species. The conservation of mutations can occur via selection pressure, mutational compensation, and/or by the separation of members from the same species by geological and environmental events. In this comprehensive study, the authors describe, a genomic landscape of the parallel evolution by analysing functional nodal mutations (fNMs) by using different types of DNA (mitochondrial and nucleic), the thermostability of mtDNA encoding RNA genes, and the structural proximity of proteins, using the available 3D structures from PDB database. Functional nodal mutations (fNMs) can be separated in single nodal (fSNMs), recurrent nodal mutations (fRNMs), occured independently in unrelated lineages and recurrent combinations of nodal mutations (fRCNMs) recurred independently along with other nodal mutations in combinations in more than a single lineage. The recurrent ones can be taken in consideration the most when we are talking about the convergent adaptive responses, that means …

Genomics / Human

Reconstructing prehistoric African population structure

November 21, 2017November 8, 2021

INTRODUCTION The highest genetic diversity in humans is found in Africa, in line with Africa being the cradle of humanity. While the three articles we discussed previously during this tutorial (1,2,3) mainly focused on determining the most parsimonious “out-of-Africa” scenarios based on genetic diversity data, this article (Skoglund et al. 2017 4) investigates the population structure of Africa prior to the expansion of food producers (i.e. herders and farmers). In order to reconstruct the prehistoric population structure, the authors analyzed the genomes from 16 ancient African individuals who lived up to 8100 years ago (including 15 newly sequenced genomes), as well as SNP genotypes from 584 present-day Africans, and 300 high coverage genomes from 142 worldwide populations. This is the first study to gather and analyze such a high number of ancient genomes, thereby providing an unpreceded insight into the prehistoric human population structure. RESULTS An ancient cline of southern and eastern African hunter-gatherers The authors used principal component analysis (PCA) and automated clustering in order to relate the 16 ancient individuals to present-day sub-Saharan Africans. This reveals that while the two ancient South African individuals share ancestry with present-day South Africans (Khoe-San), 11 of the 12 ancient individuals living …

Genomics / Human

A journey through the The Simons Genome Diversity Project: more genomes sequenced, more diverse populations

November 13, 2017November 8, 2021

Introduction Since the first genome of Bacteriophage MS21 was completely sequenced, in 1976, until 2001 when the first draft of human genome2 was released, a lot of work was done to improve and to make accessible different methods to get inside of the genetics of various organisms. For human genome, this step was a very important one and the Human Genome Project was declared complete in 20033. During the last years, more and more projects are involved in deciphering the human wanderlust. To all of previous studies, we can add The Simons Genome Diversity Project, that brought us more information by sequencing 300 new genomes from 142 diverse populations. One of the aim was to chose populations that differ in genetics, language and culture. The study shows that some of the populations separated 100000 years ago and reveals more information about the ancestors of Australian, New Guinean and Andamanese people. Results One of the most important thing in discovering the real human peopling of the Earth is to sequence as many as possible genomes, but from individuals coming from diverse populations, that could differ in many aspects. In this study, the 300 samples were prepared by using PCR-free library, through …

Genomics / Human

Genomic analyses inform on migration events during the peopling of Eurasia

October 25, 2017November 8, 2021

Introduction In the past two decades, considerable research effort has been made to sequence the human genome and subsequently trying to unveil the demographic history underlying the genetic patterns of diversity we observe today across the globe. Here we discuss a recent research article by Pagani et al. 1 that addresses genomic diversity and historic migration patterns of human populations in Eurasia. The first human genome was sequenced in 2003 by the Human Genome Project2 and larger projects rapidly followed, such as HAPMAP3 and the 1000 Genomes Project4, largely due to the considerable technological improvement of sequencing technologies. Despite being extremely useful tools for a number of studies, these genome databases have some important sampling caveats that limit their use to address some particular topics. Indeed, HAPMAP sampled a reduced number of populations whereas the 1000 Genomes sampled a large number of populations but did not attempt to sample individuals of “pure” ancestry. For instance, the sampling in North America focused considerably on city-based individuals that were found to have a very diverse recent ancestry thus blurring the signal of ancient colonisation history. Importantly, in the studied paper, a considerable effort was made on sampling a broad panel of 447 …

Evolution / Genomics / Human

ExAC presents a catalogue of human protein-coding genetic variation

December 8, 2016November 8, 2021

Exploration of variability of human genomes represents a key step in the holy grail of human genetics – to link genotypes with phenotypes, it also provides insights to human evolution and history. For this purpose Exome Aggregation Consortium (ExAC) have been founded; to capture variability of human exomes using next-generation sequencing. The first ExAC dataset of 63,358 individuals was released 20th of October 2014. Recently, a paper describing updated version of the dataset was published : Analysis of protein-coding genetic variation in 60,706 humans. Authors made a great work on the reproductibility of the downstream analyses they have performed and generally on the availability of data. All the code is well documented in blogpost and available in GitHub repository. All figures in this blogpost I plotted by my own! Dataset ExAC is composed of almost ten fold more individuals and previous dataset of the similar kind Fig 1a. 91,000 individuals were sequenced, of which 60,706 have been kept after quality filtering. Finnish population was excluded from European due to bottleneck they have gone though. ExAC was targeting individuals with various genetic background. Principal component analysis have shown very strong geographical pattern in the dataset (Fig 1b). I expected a continuum …

Genomics / Human

Identification of a large set of rare complete human knockouts

May 16, 2016November 8, 2021

High throughput genotyping and sequencing has led to the discovery of numerous sequence variants associated to human traits and diseases. An important type of variants involved are Loss of Function (LoF) mutations (frameshift indels, stop-gain and essential sites variants), which are predicted to completely disrupt the function of protein-coding genes. In case of Mendelian recessive diseases, for the condition to occur, the LoF variants must be biallelic, i.e. affecting both copies of a gene. The affected gene is then defined as “knockout”. By studying the Icelandic population, authors aim to identify rare LoF mutations (Minor Allele Frequency, MAF < 2%) present in individuals participating in various disease projects. They then investigate at which frequency in the population these LoF mutations are homozygous (i.e. knockout) in the germline genome. The Icelandic population Iceland is well-suited for genetic studies for three main reasons. The island was colonized by human population around the 9th century by 8-20 thousand settlers. Since then the population grew to around 320’000 inhabitants today. The initial founder effect and rare genetic admixture make the Icelandic population a genetic isolate. In addition to an unusual genetic isolation, Iceland’s population benefits of a genealogical database containing family histories reaching centuries …

Evolution / Genomics / Tutorial

Supergenes and social organization in a bird species

May 6, 2016November 8, 2021

Cindy Dupuis, Xinji Li, Casper van der Kooi The development of new molecular mechanisms and next generation sequencing techniques have advanced our knowledge on the genetic basis underlying phenotypic polymorphism. Over the coarse of recent years, scientific studies have documented large genomic regions with drastic phenotypic effects, the so-called supergenes. A supergene is a set of genes on the same chromosome that exhibit close genetic linkage and thus inherits as one unit. The evolution of a supergene requires that multiple loci with complementary effects become linked (i.e. they are genetically clustered and recombination between the loci is suppressed) and that optimal alleles at the linked loci are combined. Genetic clustering of different loci can occur when, via mutation, an adaptive interaction between two closely placed loci is created. In addition, gene duplications or translocations that generate a series of (novel) complementary genes can give rise to supergenes. The probability of a recombination event occurring in between loci depends on various factors. The chance of a recombination event occurring in between two loci will be small when the loci are located closely together, as the chance of a recombination event in between two loci generally decreases with …

Genomics / Human / PNAS

Reconstructing human population history : ancestry and admixture

March 31, 2016November 8, 2021

Understanding the evolutionary history of our own species, how migration and mixture of ancestral populations have shaped modern human populations is a key question in evolutionary biology. Here we present three articles related to this topic, the first two dealing with India and the third one focusing on a single Ethiopian group : 1) Moorjani et al 2013 Genetic Evidence for Recent Population Mixture in India AJHG 93,: 422–438 2) Basu et al 2016 Genomic reconstruction of the history of extant populations of India reveals five distinct ancestral components and a complex structure PNAS online before print 3) Van Dorp et al 2016 Evidence for a Common Origin of Blacksmiths and Cultivators in the Ethiopian Ari within the Last 4500 Years: Lessons for Clustering-Based Inference PLOS Genetics 11(8): e1005397 All of them use genome wide data from micro array. After a brief abstract of each paper, showing their similarities and differences, we discuss their methodological approaches. Ancestral populations of India The aim of the first two articles is to understand the history of the populations of the Indian subcontinent. The first one (Moorjani et al 2013) reports data from 73 groups living in India for more than 570 individuals sampled. …

Adaptation / Conservation / Evolution / Genomics

Evolution of Darwin’s finches and their beaks revealed by genome sequencing

May 28, 2015November 8, 2021

Introduction Darwin’s finches from Galapagos and Cocos Island are classic example of young adaptive radiation, entirely intact because none of the species having become extinct as a result of human activity. They have diversified in beak sizes and shapes, feeding habits and diets in adapting to different food resources. Although traditional taxonomy of Darwin’s is based on morphology and has been largely supported by observations of breeding birds finches, in this paper, authors showed the results of whole-genome re-sequencing of 120 individuals representing all of the Darwin’s finch species inhabiting Galapagos archipelago (Fig. 1a) and two close relatives, trying to analyse patterns of intra-and interspecific genome diversity and phylogenetic relationships among the species. Figure 1a. Sample location of Darwin’s finches Summary and comments of the paper The authors analyzed location and phylogeny of Darwin’s finches and found widespread evidence of interspecific gene flow that may have enhanced evolutionary diversification throughout phylogeny. They also reported discovery of a locus with the major effect on beak shape. They generated 10x sequence coverage per individual bird and using 2×100 base-pair (bp) paired-end reads and found evidence of introgression from three sources: ABBA-BABA tests, discrepancies between phylogenetic trees based on autosomal and sex linked …