Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

Neandertals, the closest evolutionary relatives of present-day humans, lived in large parts of Europe and western Asia before disappearing 30,000 years ago. We present a draft sequence of the Neandertal genome composed of more than 4 billion nucleotides from three individuals. Comparisons of the Neandertal genome to the genomes of five present-day humans from different parts of the world identify a number of genomic regions that may have been affected by positive selection in ancestral modern humans, including genes involved in metabolism and in cognitive and skeletal development. We show that Neandertals shared more genetic variants with present-day humans in Eurasia than with present-day humans in sub-Saharan Africa, suggesting that gene flow from Neandertals into the ancestors of non-Africans occurred before the divergence of Eurasian groups from each other.

/pdf/a-draft-sequence-of-the-neandertal-genome-4nrrmzdsiy.pdf

A Draft Sequence of the Neandertal Genome

Recent scientific discoveries that resulted from the application of nextgeneration DNA sequencing technologies highlight the striking impact of these massively parallel platforms on genetics. These new methods have expanded previously focused readouts from a variety of DNA preparation protocols to a genome-wide scale and have fine-tuned their resolution to single base precision. The sequencing of RNA also has transitioned and now includes full-length cDNA analyses, serial analysis of gene expression (SAGE)-based methods, and noncoding RNA discovery. Next-generation sequencing has also enabled novel applications such as the sequencing of ancient DNA samples, and has substantially widened the scope of metagenomic analysis of environmentally derived samples. Taken together, an astounding potential exists for these technologies to bring enormous change in genetic and biological research and to enhance our fundamental biological knowledge.

/pdf/next-generation-dna-sequencing-methods-1mt1qtnesz.pdf

Next-Generation DNA Sequencing Methods

Here we present a draft genome sequence of the common chimpanzee (Pan troglodytes). Through comparison with the human genome, we have generated a largely complete catalogue of the genetic differenc ...

/pdf/initial-sequence-of-the-chimpanzee-genome-and-comparison-l1qcac6z1b.pdf

Initial sequence of the chimpanzee genome and comparison with the human genome

The revolution that wasn't: a new interpretation of the origin of modern human behavior.

The expansion of premodern humans into western and eastern Europe ∼40,000 years before the present led to the eventual replacement of the Neanderthals by modern humans ∼28,000 years ago1. Here we report the second mitochondrial DNA (mtDNA) analysis of a Neanderthal, and the first such analysis on clearly dated Neanderthal remains. The specimen is from one of the eastern-most Neanderthal populations, recovered from Mezmaiskaya Cave in the northern Caucasus2. Radiocarbon dating estimated the specimen to be ∼29,000 years old and therefore from one of the latest living Neanderthals3. The sequence shows 3.48% divergence from the Feldhofer Neanderthal4. Phylogenetic analysis places the two Neanderthals from the Caucasus and western Germany together in a clade that is distinct from modern humans, suggesting that their mtDNA types have not contributed to the modern human mtDNA pool. Comparison with modern populations provides no evidence for the multiregional hypothesis of modern human evolution.

Molecular analysis of Neanderthal DNA from the northern Caucasus

LINE-1 (L1) elements play an important creative role in genomic evolution by distributing both L1 and non-L1 DNA in a process called retrotransposition. A large percentage of the human genome consists of DNA that has been dispersed by the L1 transposition machinery. L1 elements are not randomly distributed in genomic DNA but are concentrated in regions with lower GC content. In an effort to understand the consequences of L1 insertions, we have begun an investigation of their genomic characteristics and the changes that occur to them over time. We compare human L1 insertions that were created either during recent human evolution or during the primate radiation. We report that L1 insertions are an important source for the creation of new microsatellites. We provide evidence that L1 first strand cDNA synthesis can occur from an internal priming event. We note that in contrast to older L1 insertions, recent L1s are distributed randomly in genomic DNA, and the shift in the L1 genomic distribution occurs relatively rapidly. Taken together, our data indicate that strong forces act on newly inserted L1 retrotransposons to alter their structure and distribution.

/pdf/genomic-characterization-of-recent-human-line-1-insertions-x61tk0mwv2.pdf

Genomic characterization of recent human LINE-1 insertions: evidence supporting random insertion.

The amplification of DNA by LINE-1 (L1) retrotransposons has created a large fraction of the human genome. To better understand their role in human evolution we endeavored to delineate the L1 elements that have amplified since the emergence of the hominid lineage. We used an approach based on shared sequence variants to trace backwards from the currently amplifying Ta subfamily. The newly identified groups of insertions account for much of the molecular evolution of human L1s. We report the identification of a L1 subfamily that amplified both before and after the divergence of humans from our closest extant relatives. Progressively more modern groups of L1s include greater numbers of insertions. Our data are consistent with the hypothesis that the rate of L1 amplification has been increasing during recent human evolution.

https://www.pnas.org/content/pnas/99/16/10522.full.pdf

Tracing the LINEs of human evolution

Editor—Wilson disease (WD), or hepatolenticular degeneration, is an autosomal recessive disorder of copper transport characterised by toxic accumulation of copper in a number of organs, principally the liver, brain, and kidney.1 An effective treatment strategy in patients with WD is based on removal of excess copper by chelating agents or zinc salts.

The gene for WD, originally assigned to chromosome 13 by linkage studies,2 was recently cloned and encodes a putative copper transporting P type ATPase (ATP7B).3 4 To date, more than 50 disease specific mutations have been identified in a number of WD patients from different countries.5 6 Some of these mutations were reported to be frequent in specific populations, which may help to introduce rapid diagnostic procedures based on direct DNA analysis into routine clinical practice. One of the most common mutations, His1069Gln, accounts for 22-31% of the WD chromosomes in European and American …

The His1069Gln mutation in the ATP7B gene in Russian patients with Wilson disease.

The genomic evolution and causes of phenotypic variation among humans and great apes remain largely unknown, although the phylogenetic relationships among them have been extensively explored. Previous studies that focus on differences at the amino acid and nucleotide sequence levels have revealed a high degree of similarity between humans and chimpanzees, suggesting that other types of genomic change may have contributed to the relatively large phenotypic differences between them. For example, the activity of long interspersed element 1 (LINE-1) retrotransposons may impose significant changes on genomic structure and function and, consequently, on phenotype. Here we investigate the relative rates of LINE-1 amplification in the lineages leading to humans, bonobos (Pan paniscus), and chimpanzees (P. troglodytes). Our data indicate that LINE-1 insertions have accumulated at significantly greater rates in bonobos and chimpanzees than in humans, provide insights into the timing of major LINE-1 amplification events during great ape evolution, and identify a Pan-specific LINE-1 subfamily.

https://www.cell.com/ajhg/pdf/S0002-9297(07)60591-6.pdf

Igor V. Ovchinnikov

Papers

Molecular analysis of Neanderthal DNA from the northern Caucasus

Genomic characterization of recent human LINE-1 insertions: evidence supporting random insertion.

Tracing the LINEs of human evolution

The His1069Gln mutation in the ATP7B gene in Russian patients with Wilson disease.

Large Differences between LINE-1 Amplification Rates in the Human and Chimpanzee Lineages