HEREDITY AND VARIABILITY
(see also paleoanthropology)

The oldest verified sample of DNA has been pulled from soil deep within the permafrost of Siberia. The DNA belonged to grasses, sedges and shrubs estimated to be between 300,000 and 400,000 years oldref.
The most ancient identified animal genetic material is about 50,000 years old. Although there is evidence of plants and animals dating back hundreds of millions of years, DNA from such specimens has not been identified because it has degraded.
Palaeomicrobiology is an emerging field that is devoted to the detection, identification and characterization of microorganisms in ancient remains. Data indicate that host-associated microbial DNA can survive for almost 20,000 years, and environmental bacterial DNA preserved in permafrost samples has been dated to 400,000-600,000 years. In addition to frozen and mummified soft tissues, bone and dental pulp can also be used to search for microbial pathogens. Various techniques, including microscopy and immunodetection, can be used in palaeomicrobiology, but most data have been obtained using PCR-based molecular techniques. Infections caused by bacteria, viruses and parasites have all been diagnosed using palaeomicrobiological techniques. Additionally, molecular typing of ancient pathogens could help to reconstruct the epidemiology of past epidemics and could feed into current models of emerging infections, therefore contributing to the development of appropriate preventative measuresref

Evolution : a process of development in which an organ or organism becomes more and more complex by the differentiation of its parts; a continuous and progressive change according to certain laws and by means of resident forces

Heredity arises from inherited ... Variability among species and among individuals of a same species arises from ... Genes that were thought to have evolved in vertebrates have been found in the flatworm Schmidtea mediterranearef. About 500 out of 1,300 ESTs from the coral Acropora millepora are shared : 90% are present in humans (including genes that contribute to the specialized tissues of vertebrate nervous systems, even though coral has only a simple nerve net), and about 10% are found in humans but not in the fruitfly Drosophila melanogaster or the nematode worm Caenorhabditis elegans. This finding suggests that many genes thought to be vertebrate-specific may in fact have much older origins, and have been lost during the evolution of the fly and worm. But the idea that some animals may discard genes as they become more sophisticated is still controversial. The finding means that although fly and worm models are useful for studying gene function in development and cellular processes, they may be of limited value in studies of the evolution of human genes. We need to look at many other animal genomes that haven't undergone the same degree of gene loss to understand the evolution and function of human genes, and how they generate complexity.

Males continually evolve novel adaptations to entice females to mate with them rather than with other males, and females continually evolve novel strategies to resist these manipulations. It is suggested that this sexual conflict could be the strongest driver of speciation. In larger, denser populations with more sexual conflict there is a very rapid evolution of female willingness to mate and of male traits that promote mating. In pairings between different populations (within conflict treatments), females show greater resistance and copulate less than within populations, indicating female preference for males from their own population.

With about 180 million years of independent evolution separating humans from the jumping marsupials, there are few mammals that are more distant from us than kangaroos (Macropus sp.) : the platypus (Ornithorhynchus anatinus) is even more distantly related, and they're going to be important too, but the platypus isn't your normal experimental animal as they are nearly impossible to breed in captivity.

The human and chimpanzees (Pan troglodytes) genomes are about 98.5-99.2% identical. In the most important bits of the genome, this figure rises to 99.5%. Despite their high degree of genomic similarity, reminiscent of their relatively recent separation from each other (approximately 5-6 million years ago), the molecular basis of traits unique to humans vs. their closest relative, the chimpanzee, is largely unknown. So the old idea was that all the things that differentiate us from apes, such as highly developed cognitive functions, walking upright and the use of complex language, should come from the other 1.5%. But the detailed sequences of chimp chromosome 22 and human chromosome 21 are roughly equivalent : out of the bits that line up, 1.44% of the individual base pairs were different, settling a debate based on previous, less accurate studies. Because chimps and humans appear broadly similar, some have assumed that most of the differences would occur in the large regions of DNA that do not appear to have any obvious function. But many of the differences were within genes : 83% of the 231 genes compared had differences that affected the amino acid sequence of the protein they encoded. And 20% showed significant structural changes. In addition, there were nearly 68,000 regions that were either extra or missing between the 2 sequences, accounting for around 5% of the chromosome. 20% of the genes showed significant differences in their pattern of activity. Chromosome 22 makes up only 1% of the genome, so in total there could be thousands of genes that significantly differ between humans and chimps : this could make it much harder than scientists had hoped to find the key changes that made us humanref. About 1,500 genes seem to have been affected by selection :

Only 9 AluYb8 DNA repeats are found in the chimpanzee genome compared to over 2200 repeats in the human, which represents a 250-fold increase in the rate of change in the human lineage and far outweighs the 99% sequence similarity between the two species. It is estimated that the average age of the human Yb8Alus is about 3.3 million years (My); almost 10% of them are identical in sequence, and hence are of recent origin. Genomic variations of this magnitude, distinguishing humans from great apes have not been realized. This explosive Alu expansion must have had a profound effect on the organization of our genome and the architecture of our chromosomes, inferentially altering profiles of gene expression and chromosome choreography in cell division. This major evolutionary process of Alu proliferation is driven by internal forces, written in the chemistry of DNA, rather than by external selectionref.
Despite 99% identity between human and chimpanzee DNA sequences, there is virtually no overlap between these two species in the locations of their recombination hotspots. Traditionally, gene mapping in humans has relied on the direct observation of recombination events in families (linkage analysis). This approach, while enormously successful, is limited by the small number of generations during which meiosis can be observed in humans. An alternative approach, based on the once-obscure concept of linkage disequilibrium (LD), has gained widespread attention during the past couple of decades. To understand LD, imagine that a disease-causing mutation has just occurred in a population. The chromosome on which this mutation occurred contains specific DNA variants (alleles) in neighboring polymorphic (variable) loci. At first, the mutation will be observed only in conjunction with these alleles, so the association (or LD) between the mutation and the surrounding variants will be high. Through time, these associations will dissipate because of recombinations between the mutation and nearby loci, and LD will drop. The closest loci will experience the fewest recombinations and hence retain higher levels of LD with the mutation. Thus, LD patterns can reveal the approximate locations of disease- causing mutations. LD analysis, in contrast to linkage analysis, reflects the effects of dozens or hundreds of past generations of recombination and may therefore confer improved resolution and statistical power to localize mutations. Although its merits are still debatedref, LD analysis may be especially useful in the detection of mutations that underlie complex diseases, and it has yielded some recent successesref1, ref2. As with all explorations, gene hunting based on LD benefits from a good map. The principal goal of the much-discussed International Haplotype Map (HapMap) Projectref is to generate such a map and to identify chromosomal regions, or "haplotype blocks," in which LD is maintained at a high level in populations. By knowing which polymorphic loci are highly correlated with one another, investigators can avoid the wasteful collection of redundant information when searching for disease-causing mutations. The LD patterns revealed by the HapMap Project and other studies have shown that recombinations appear to be concentrated in specific regions known as hotspots, which are found once every 50 to 200 kb in the human genomeref1, ref2. A hotspot is defined as a 1- to 2-kb region in which the recombination rate, estimated here by LD, is at least 10 times that in the surrounding regionref. A better understanding of hotspots could have important implications for our ability to discover and exploit haplotype blocks (for example, determining how often haplotype blocks are defined by hotspots).  Mapping recombination hotspots. (A) Hypothetical ancestral chromosomes contain a series of polymorphic loci with alleles A, a; B, b; C, c and so on. If recombination occurs in a relatively uniform fashion, markers that are close to one another will maintain high levels of linkage disequilibrium (for example, loci A and B). In contrast, markers that are more distant will have low levels of linkage disequilibrium because of multiple intervening recombinations (for example, loci A and N). A mutation that occurs on the ancestral chromosome near loci L and M will be found in association only with those alleles in a chromosome sampled from the present population. (B) If recombination is concentrated in hotspots, linkage disequilibrium will be preserved over longer distances across the chromosome (haplotype blocks). Thus, loci A, B, C, and D will retain a high degree of linkage disequilibrium, but between loci D and E linkage disequilibrium will break down rapidly because of multiple recombinations that occur at the hotspot. The mutation located between loci L and M is associated with polymorphic loci over a longer chromosome distance (K, L, M, and N). In their new work, Winckler et al.ref have addressed this goal by using LD-based methods to compare hotspot locations in 1.5 megabases (Mb) of orthologous DNA sequences from the human and chimpanzee genomes. Human and chimpanzee DNA sequences are almost 99% identical. Thus, if hotspots are sequence-dependent, one might expect a high degree of concordance in their locations. Instead, Winckler et al. found that 18 recombination hotspots revealed in the human genome were absent from the chimpanzee genome. Hotspots in the human -globin and human leukocyte antigen gene regions were also found to be absent in chimpanzees. The three recombination hotspots found in chimpanzees were absent in humans. Another recent study revealed the same lack of concordanceref. What could account for this? One possibility is that LD, which can be affected by evolutionary processes such as natural selection, genetic drift, and admixtureref, is not a reliable indicator of recombination hotspots. Indeed, it is possible to generate haplotype blocks through genetic drift aloneref. However, Winckler et al. show that European and African populations, which have quite different demographic histories, reveal a high degree of concordance in the locations of hotspots (although, as in all such studies, there is generally more LD in the European than in the African sample). Other studies report generally similar findingsref1, ref2. Even more convincingly, LD-based methods are quite successful in detecting hotspots previously documented by the direct assessment of recombination events in sperm cellsref1, ref2. Although the effects of human population history appear not to account for hotspot locations, it is possible that hotspot discordance could result from the substantial differences seen in the demographic histories or population structures of humans and chimpanzeesref. Winckler et al. used the well-known STRUCTURE algorithm to demonstrate a lack of population structure in the chimpanzee sample, but the number of loci they used (40) may be insufficient to detect meaningful population subdivisionref. Sperm typing in chimpanzees would allow a direct examination of recombination hotspots (at least in males) and would more conclusively exclude population structure and demographic history as explanatory factors. As with any statistical analysis, the power to detect hotspots should be considered. Whereas the sample sizes on which most of the analyses are based are reasonably large (90 European-derived and 90 African individuals), the sample of 38 western chimpanzees is relatively small, as is the amount of DNA sequence (3 500-kb regions in the primary analysis). The authors have addressed this issue extensively and have shown that a lack of power would be unlikely to account for the startling absence of hotspot concordance. Also supporting their findings are the congruent results of Ptak et al.ref, which were based on an assessment of 14 Mb of DNA sequence in 71 humans but only eight chimpanzees. Still another possible explanation for these results lies in genomic factors that are known to correlate with recombination rates. Recombination is elevated in GC-rich regions of the genome, and human recombination rates tend to be lower near centromeres and higher near telomeresref1, ref2. In addition, the overall human recombination rate is about 60% greater in female than in male meiosis. These factors, while related to recombination rates over relatively large regions, do not appear to correlate strongly with recombination hotspots in humansref1, ref2. Lacking evidence that population history or local DNA sequence variation can account for hotspot location, Winckler et al. suggest that epigenetic factors that influence chromatin configuration (for example, acetylation and methylation) may be the key. Here it is useful to consider the budding yeast Saccharomyces cerevisiae, which has provided much of our knowledge about eukaryotic recombination. In yeast, meiotic recombination is initiated by DNA double-strand breaks, which occur in relatively open chromatin regionsref1, ref2. The same appears to be true of mammalian recombination. Furthermore, many of the proteins necessary for this process, such as the DNA topoisomerase-related enzyme Spo11, are highly conserved from yeast to mammalsref. Yeast recombination hotspots occur roughly once every 50 kbref, and, as in mammals, they do not appear to be consistently associated with specific DNA sequence motifsref. These comparisons suggest a number of potentially useful studies. Although technically challenging, it may prove fruitful to examine regional variation in chromatin accessibility in mammalian meiotic cells. How does this affect the action of recombination-related proteins such as Spo11? In addition to Spo11, at least 11 other proteins are involved in the initiation of double-strand breaks and recombination in yeastref, and many of the responsible genes have orthologs in humans (such as, RAD50, RAD51, and MRE11). Comparisons of these genes in humans and chimpanzees could reveal differences that affect recombination patterns. In yeast, recombination hotspots can be eliminated by the insertion of the Ty transposable element, which suppresses recombination in nearby sequencesref. Thousands of Alu and LINE1 mobile elements have been differentially inserted in humans and chimpanzees since their divergence 5 million to 6 million years agoref. Could these elements act in a fashion similar to yeast Ty, contributing to the rapid divergent evolution of recombination hotspots in humans and chimpanzees? Studies such as that by Winckler et al. demonstrate the value of comparative genomic analysis for understanding basic biological processes such as recombination, and for potentially improving the design of genetic association studies. Their work also demonstrates the utility of analyses of within-species diversity and underscores the need for DNA sequence information from large samples of humans and other species. As this information accumulates, our understanding of biology, as well as our ability to design well-conceived gene-mapping studies, will continue to evolve and improveref.

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