Chimp Genome Research Articles

Insertion-Deletion Events Are Depleted in Protein Regions with Predicted Secondary Structure.

A fundamental goal in evolutionary biology and population genetics is to understand how selection shapes the fate of new mutations. Here, we test the null hypothesis that insertion-deletion (indel) events in protein-coding regions occur randomly with respect to secondary structures. We identified indels across 11,444 sequence alignments in mouse, rat, human, chimp, and dog genomes and then quantified their overlap with four different types of secondary structure-alpha helices, beta strands, protein bends, and protein turns-predicted by deep-learning methods of AlphaFold2. Indels overlapped secondary structures 54% as much as expected and were especially underrepresented over beta strands, which tend to form internal, stable regions of proteins. In contrast, indels were enriched by 155% over regions without any predicted secondary structures. These skews were stronger in the rodent lineages compared to the primate lineages, consistent with population genetic theory predicting that natural selection will be more efficient in species with larger effective population sizes. Nonsynonymous substitutions were also less common in regions of protein secondary structure, although not as strongly reduced as in indels. In a complementary analysis of thousands of human genomes, we showed that indels overlapping secondary structure segregated at significantly lower frequency than indels outside of secondary structure. Taken together, our study shows that indels are selected against if they overlap secondary structure, presumably because they disrupt the tertiary structure and function of a protein.

The Cumulative Indel Model: Fast and Accurate Statistical Evolutionary Alignment.

Sequence alignment is essential for phylogenetic and molecular evolution inference, as well as in many other areas of bioinformatics and evolutionary biology. Inaccurate alignments can lead to severe biases in most downstream statistical analyses. Statistical alignment based on probabilistic models of sequence evolution addresses these issues by replacing heuristic score functions with evolutionary model-based probabilities. However, score-based aligners and fixed-alignment phylogenetic approaches are still more prevalent than methods based on evolutionary indel models, mostly due to computational convenience. Here, I present new techniques for improving the accuracy and speed of statistical evolutionary alignment. The “cumulative indel model” approximates realistic evolutionary indel dynamics using differential equations. “Adaptive banding” reduces the computational demand of most alignment algorithms without requiring prior knowledge of divergence levels or pseudo-optimal alignments. Using simulations, I show that these methods lead to fast and accurate pairwise alignment inference. Also, I show that it is possible, with these methods, to align and infer evolutionary parameters from a single long synteny block (n}{}approx530 kbp) between the human and chimp genomes. The cumulative indel model and adaptive banding can therefore improve the performance of alignment and phylogenetic methods. [Evolutionary alignment; pairHMM; sequence evolution; statistical alignment; statistical genetics.]

What makes humans human? a review of important genetic differences between chimpanzees and humans

What makes humans human? Genomic comparisons of humans and chimpanzees provide a new tool for addressing this interesting question. Genetic comparisons show remarkable similarity between chimpanzees and humans; indeed, the human and chimp genome are 96% similar, with only a 1% difference in nucleotide substitutions and a 3% difference in chromosomal insertions and deletions. But even modest differences in genomes can have profound biological effects. In this review, we tackle this formidable topic by summarizing the effects of transposon mobility, uniquely human genes and small nucleotide changes in conferring important phenotypic changes from chimpanzee to human.

A complex genome-microRNA interplay in human mitochondria.

Small noncoding regulatory RNA exist in wide spectrum of organisms ranging from prokaryote bacteria to humans. In human, a systematic search for noncoding RNA is mainly limited to the nuclear and cytosolic compartments. To investigate whether endogenous small regulatory RNA are present in cell organelles, human mitochondrial genome was also explored for prediction of precursor microRNA (pre-miRNA) and mature miRNA (miRNA) sequences. Six novel miRNA were predicted from the organelle genome by bioinformatics analysis. The structures are conserved in other five mammals including chimp, orangutan, mouse, rat, and rhesus genome. Experimentally, six human miRNA are well accumulated or deposited in human mitochondria. Three of them are expressed less prominently in Northern analysis. To ascertain their presence in human skeletal muscles, total RNA was extracted from enriched mitochondria by an immunomagnetic method. The expression of six novel pre-miRNA and miRNA was confirmed by Northern blot analysis; however, low level of remaining miRNA was found by sensitive Northern analysis. Their presence is further confirmed by real time RT-PCR. The six miRNA find their multiple targets throughout the human genome in three different types of software. The luciferase assay was used to confirm that MT-RNR2 gene was the potential target of hsa-miR-mit3 and hsa-miR-mit4.

Jocks versus geeks--the downside of genius?

Jocks versus geeks--the downside of genius?

Genes & cells: Going ape offers better family tree: Gorilla, chimp genomes suggest twists in primate evolution

Science NewsVolume 181, Issue 8 p. 16-16 In the News Genes & cells: Going ape offers better family tree: Gorilla, chimp genomes suggest twists in primate evolution Tina Hesman Saey, Tina Hesman SaeySearch for more papers by this author Tina Hesman Saey, Tina Hesman SaeySearch for more papers by this author First published: 12 April 2012 https://doi.org/10.1002/scin.5591810820Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume181, Issue821 April 2012Pages 16-16 RelatedInformation

Clinical implications of human population differences in genome-wide rates of functional genotypes.

There have been a number of recent successes in the use of whole genome sequencing and sophisticated bioinformatics techniques to identify pathogenic DNA sequence variants responsible for individual idiopathic congenital conditions. However, the success of this identification process is heavily influenced by the ancestry or genetic background of a patient with an idiopathic condition. This is so because potential pathogenic variants in a patient’s genome must be contrasted with variants in a reference set of genomes made up of other individuals’ genomes of the same ancestry as the patient. We explored the effect of ignoring the ancestries of both an individual patient and the individuals used to construct reference genomes. We pursued this exploration in two major steps. We first considered variation in the per-genome number and rates of likely functional derived (i.e., non-ancestral, based on the chimp genome) single nucleotide variants and small indels in 52 individual whole human genomes sampled from 10 different global populations. We took advantage of a suite of computational and bioinformatics techniques to predict the functional effect of over 24 million genomic variants, both coding and non-coding, across these genomes. We found that the typical human genome harbors ∼5.5–6.1 million total derived variants, of which ∼12,000 are likely to have a functional effect (∼5000 coding and ∼7000 non-coding). We also found that the rates of functional genotypes per the total number of genotypes in individual whole genomes differ dramatically between human populations. We then created tables showing how the use of comparator or reference genome panels comprised of genomes from individuals that do not have the same ancestral background as a patient can negatively impact pathogenic variant identification. Our results have important implications for clinical sequencing initiatives.

Non-B DB: a database of predicted non-B DNA-forming motifs in mammalian genomes

Although the capability of DNA to form a variety of non-canonical (non-B) structures has long been recognized, the overall significance of these alternate conformations in biology has only recently become accepted en masse. In order to provide access to genome-wide locations of these classes of predicted structures, we have developed non-B DB, a database integrating annotations and analysis of non-B DNA-forming sequence motifs. The database provides the most complete list of alternative DNA structure predictions available, including Z-DNA motifs, quadruplex-forming motifs, inverted repeats, mirror repeats and direct repeats and their associated subsets of cruciforms, triplex and slipped structures, respectively. The database also contains motifs predicted to form static DNA bends, short tandem repeats and homo(purine•pyrimidine) tracts that have been associated with disease. The database has been built using the latest releases of the human, chimp, dog, macaque and mouse genomes, so that the results can be compared directly with other data sources. In order to make the data interpretable in a genomic context, features such as genes, single-nucleotide polymorphisms and repetitive elements (SINE, LINE, etc.) have also been incorporated. The database is accessed through query pages that produce results with links to the UCSC browser and a GBrowse-based genomic viewer. It is freely accessible at http://nonb.abcc.ncifcrf.gov.

The fickle Y chromosome

Chimp genome reveals rapid rate of change.

Stepwise evolution of two giant composite LTR-retrotransposon-like elements DA and Xiao

BackgroundWe recently discovered two composite long terminal repeat (LTR)-retrotransposon-like elements which we named DA (~300 kb) and Xiao (~30 kb), meaning big and small in Chinese respectively. Xiao and DA (three types of DA identified) were found to have been derived from several donor sites and have spread to 30 loci in the human genome, totaling to 5 Mb. Our bioinformatics analyses with the released human, chimp, rhesus macaque, orangutan, and marmoset genomic sequences indicate that DA and Xiao emerged ~25 million years (Myr) ago.ResultsTo better understand the evolution of these two complex elements, we investigated various internal junctions of DA and Xiao as well as orthologous genomic sites of the 30 DA/Xiao loci in non-human primates including great apes, lesser apes, Old World monkeys, New World monkeys, and a prosimian. We found that Xiao and type I DA first emerged in the genome between 25 and 18 Myr ago, whereas type II and Type III DAs emerged between 14 and 7 Myr ago. Xiao and DA were most active in great apes, with their amplification peaking during 25-14 and 14-7 Myr ago, respectively. Neither DA nor Xiao seem to have been active in the human and chimp genomes during last 6 Myr.ConclusionThe study has led to a more accurate age determination of the DA and Xiao elements than our previous bioinformatics analyses, and indicates that the amplification activity of the elements coincided with that of group I HERV-Es during evolution. It has also illustrated an evolutionary path with stepwise structural changes for the elements during past 25 Myr, and in doing so has shed more light on these two intriguing and complex elements that have reshaped our genome.

The Longest (A+T) and (G+C) Blocks in the Human and Other Genomes

We analysed complete or almost complete nucleotide sequences of the human, chimp, mouse, rat, chicken, dog, and other genomes to find that they contain extremely long (A+T) a (G+C) blocks that do not occur at all in the corresponding randomized sequences. The longest is an (A+T) block containing 1040 consecutive AT pairs that occurs in the 16th human chromosome. The longest human (G+C) block has 261 bp in length. About a half of the longest blocks occur in introns. The (A+T) blocks are discrete units whereas the (G+C) blocks are diffuse. They are embeeded in the genome through connectors longer than 1 kilobase where the (G+C) content gradually decreases to the value of 50%. Remarkably, the (A+T) as well as (G+C) blocks are substantially shorter in the chimp genome. Chicken is characteristic by very long (G+C) blocks that are even longer than in the human genome. Though much shorter, long (G+C) and especially (A+T) blocks occur in lower organisms as well, which means that AT and GC pair clustering is an ancient property that has evolved into large scales in higher eukaryote genomes and the human genome in particular. Very long (A+T) and (G+C) blocks confer specific biophysical properties on DNA that are likely to influence genome folding in cell nuclei and its functional properties.

The Joint Allele-Frequency Spectrum in Closely Related Species

We develop the theory for computing the joint frequency spectra of alleles in two closely related species. We allow for arbitrary population growth in both species after they had a common ancestor. We focus on the case in which a single chromosome is sequenced from one of the species. We use classical diffusion theory to show that, if the ancestral species was at equilibrium under mutation and drift and a chromosome from one of the descendant species carries the derived allele, the frequency spectrum in the other species is uniform, independently of the demographic history of both species. We also predict the expected densities of segregating and fixed sites when the chromosome from the other species carries the ancestral allele. We compare the predictions of our model with the site-frequency spectra of SNPs in the four HapMap populations of humans when the nucleotide present in the Neanderthal DNA sequence is ancestral or derived, using the chimp genome as the outgroup.

Neanderthal genome sees first light

Initial sequences sheds light on common ancestor. Neanderthal traits appear in the human fossil record of Europe and western Asia about 400,000 years ago and vanish about 30,000 years ago. The Neanderthals are our closest extinct relatives, so as DNA technology advances the tantalizing prospect of identifying genetic changes characteristic of fully modern humans comes closer. A 38,000-year-old Neanderthal bone of sufficiently high quality to allow the extraction of more than a million base pairs has now been identified: it was originally found Vindija cave in Croatia (pictured on the cover) in 1980. Comparison of its DNA with the chimp and human genomes reveals that Neanderthal and human ancestors — like humans but unlike apes — had a small effective population size. The technology used in this work offers the prospect of a draft Neanderthal genome within two years.

The Jewels of Our Genome: The Search for the Genomic Changes Underlying the Evolutionarily Unique Capacities of the Human Brain

The recent publication of the initial sequence and analysis of the chimp genome allows us, for the first time, to compare our genome with that of our closest living evolutionary relative. With more primate genome sequences being pursued, and with other genome-wide, cross-species comparative techniques emerging, we are entering an era in which we will be able to carry out genomic comparisons of unprecedented scope and detail. These studies should yield a bounty of new insights about the genes and genomic features that are unique to our species as well as those that are unique to other primate lineages, and may begin to causally link some of these to lineage-specific phenotypic characteristics. The most intriguing potential of these new approaches will be in the area of evolutionary neurogenomics and in the possibility that the key human lineage–specific (HLS) genomic changes that underlie the evolution of the human brain will be identified. Such new knowledge should provide fresh insights into neuronal development and higher cognitive function and dysfunction, and may possibly uncover biological mechanisms for information storage, analysis, and retrieval never previously seen.

Positive Selection, Relaxation, and Acceleration in the Evolution of the Human and Chimp Genome

For years evolutionary biologists have been interested in searching for the genetic bases underlying humanness. Recent efforts at a large or a complete genomic scale have been conducted to search for positively selected genes in human and in chimp. However, recently developed methods allowing for a more sensitive and controlled approach in the detection of positive selection can be employed. Here, using 13,198 genes, we have deduced the sets of genes involved in rate acceleration, positive selection, and relaxation of selective constraints in human, in chimp, and in their ancestral lineage since the divergence from murids. Significant deviations from the strict molecular clock were observed in 469 human and in 651 chimp genes. The more stringent branch-site test of positive selection detected 108 human and 577 chimp positively selected genes. An important proportion of the positively selected genes did not show a significant acceleration in rates, and similarly, many of the accelerated genes did not show significant signals of positive selection. Functional differentiation of genes under rate acceleration, positive selection, and relaxation was not statistically significant between human and chimp with the exception of terms related to G-protein coupled receptors and sensory perception. Both of these were over-represented under relaxation in human in relation to chimp. Comparing differences between derived and ancestral lineages, a more conspicuous change in trends seems to have favored positive selection in the human lineage. Since most of the positively selected genes are different under the same functional categories between these species, we suggest that the individual roles of the alternative positively selected genes may be an important factor underlying biological differences between these species.

When Less Is More: Losing Genes on the Path to Becoming Human

Students of human evolution got a big boost when the draft sequence of the chimp genome was published in 2005. Now their challenge is to comb through the combined 6 billion nucleotides for clues to the evolutionary forces that made humans odd man out in the primate family tree. Chimp and human DNA nucleotides differ by just 1.23%, sufficient genetic variation for natural selection to create a bipedal, big-brained primate lineage but small enough to suggest that every mutation has an evolutionary tale to tell.

Evolution: Natural Selection in the Evolution of Humans and Chimps

We now have more or less full sequences of both human and chimp genomes, allowing comparison that sheds light on their evolution. A few hundred genes show significant evidence for adaptive evolution in the two lineages, but the actual number might be much higher. Natural selection has eliminated about 75% of amino acid changes in coding sequence since the split of the human and chimpanzee genomes.

Chimp Genome Catalogs Differences With Humans

GENOMICSInternational teams of researchers have produced a rough draft of the chimpanzee DNA sequence, aligned it with the human one, and made an intimate comparison of the chimp and human genomes.

Thoughts on the Future of Great Ape Research

In their Perspective, [McConkey and Varki][1] discuss the sequencing of the chimp genome, reported this week in the journal Nature . Although it is a notable accomplishment, it only marks the end of the beginning. The hard work of understanding how the genome generates the chimp phenome is still ahead of us, as is clarification of the precise differences between chimps and humans. [1]: http://www.sciencemag.org/cgi/content/full/309/5740/1499

Evolution of the spermadhesin gene family

Spermadhesins belong to a novel family of secretory proteins of the male genital tract. They are major proteins of the seminal plasma and have been found peripherally associated to the sperm surface. So far, they have only been detected in ungulates, specifically in pig, cattle, and horse, respectively. Spermadhesins form a subgroup of the superfamily of proteins with a CUB-domain that has been found in a variety of developmentally regulated proteins. The structure and function of the spermadhesins have been investigated in the pig. They are multifunctional proteins showing a range of ligand-binding abilities, e.g. to carbohydrates, phospholipids, and protease inhibitors, suggesting that they may be involved in different steps of fertilization. We report here the genomic organization of the porcine spermadhesin gene cluster as well as a detailed comparative analysis with respect to other mammalian species. The porcine spermadhesin genes are located on SSC 14q28–q29 in a region syntenic to HSA 10q26. The pig contains five closely linked spermadhesin genes, whereas only two spermadhesin genes are present in the cattle genome. Inactive copies of spermadhesin genes are still detectable in the human, chimp, and dog genome while the corresponding region was lost from the rodent genomes of mouse and rat. Within the pig, the five spermadhesin genes contain both highly diverged and highly conserved regions. Interestingly, the pattern of divergence does not correlate with the position of the exons. Evolutionary analyses suggest that the pattern of diversity is shaped by ancestral variation, recombination, and new mutations.