Nature Genetics pp 127 - 128

Sheep, mice, cows and goats have now been successfully cloned by transferring nuclei from different types of cells into separate cells, and the techniques of cloning are becoming more widely available for a variety of biotechnological applications. But despite its successes, the technology is still inefficient, because many of the factors that affect cloning are not well understood. For example, it is unclear why only the nuclei from certain adult cell types, typically those from the female reproductive system, have produced viable clones. The result? Only female animals have been reported in the scientific literature.

Until now, that is. Teruhiko Wakayama and Ryuzo Yanagimachi (of the University of Hawaii) - who cloned the first mouse (a female, Cumulina) from female 'cumulus' cells in 1997 - now report the cloning of the first male mouse. The authors explored the efficacy of cloning mice using different cell types, including some from the tails of male mice, from which the first male, nicknamed "Fibro" (short for "fibroblast", the type of cell from which he probably was derived) was cloned. He is completely normal in all respects, including body weight, growth and fertility. These findings show that cloning of mammals from adult cells is not restricted to those from females, and males' (and females') tails may serve as a ready source of DNA for future mouse cloning experiments.

Nature Genetics pp 164 - 167 and pp 119 - 120

Some of us look at a chimpanzee, and think (a bit anthropocentrically) that humans, chimpanzees and gorillas are nothing alike. But looks can be deceiving. The genomes of chimps, humans and gorillas are very similar, with only 1.5% of the total DNA bases differing between chimps and humans and only 2.1% differing between gorillas and humans. Still, the known variances in DNA sequence have not been very informative for determining how closely related we are to chimps and gorillas, because the precise distribution of sequence differences between species, and individuals within species, is poorly understood. Technological advances, such as microarray analysis, offer researchers a new possibility: the ability to survey a large amount of DNA simultaneously in many individual humans and apes.

Some DNA bases vary between individuals; this small degree of DNA variation is the reason why you don't look exactly like anyone else (assuming you don't have an identical twin). Now, Joseph Hacia and Francis Collins (of the National Human Genome Research Institute) and colleagues have extended the analysis to chimps and gorillas. In cases where two possible bases could occupy a single site in the DNA sequence, one of the two is typically shared with close primate relatives and is therefore considered 'ancestral'. The frequency with which the ancestral base appears in populations of two species indicates the amount of time that has elapsed since two given species diverged on the evolutionary tree. Using microarrays, Hacia and colleagues found that, at the majority of sites examined, the same base was common to human, chimp and gorilla.

These findings will allow us to re-evaluate estimates of how different (or similar) humans and close primate relatives really are in terms of DNA sequence, as well as helping to refine existing models of when species evolved from common ancestors. As pointed out by Andrew Clark (of the Pennsylvania State University) in an accompanying News & Views article, knowing the 'ancestral genome' may also provide insight into human migration, population expansion and the origin of mutations associated with diseases that afflict modern day humans.

Nature Genetics pp 145 - 150 and pp 120 - 121

Malaria is one of the most deadly infectious diseases, killing up to one million people each year. The disease is caused by the parasite Plasmodium falciparum, which infects red blood cells. But not everyone is equally susceptible to infection by the malarial parasite. Mutant versions of some genes, such as the haemoglobin gene, which is mutated in sickle-cell anaemia, can protect against malarial infections by altering the ability of the parasite to successfully infect the host. More recently, variants of genes that actually make the carriers more susceptible to malarial infection have been characterized. But exactly why these gene variants lead to greater malarial susceptibility has remained a mystery.

Dominic Kwiatkowski (of the Institute of Molecular Medicine) and colleagues now present an explanation for why at least one gene variant leads to increased susceptibility to malaria. A single DNA base change in the TNF gene is associated with greater risk of disease in an African population in the Gambia. The TNF gene encodes tumour necrosis factor, one of the cytokines, a class of factors involved in mediating the immune response. Surprisingly, the base change does not alter the sequence of the protein encoded by the gene; rather, the change is in the 'promoter' region of TNF, which is responsible not only for controlling when the gene is turned on and off, but also how much product is made. This base change results in increased levels of TNF, which in turn appear to predispose to malarial infection.

But the story is not quite that simple. Individuals with the first base change always have a second base change in TNF, also in the promoter region. This second change appears to ameliorate the effects of the first change in the Kenyan, but not Gambian, population. Mats Wahlgren (of the Karolinska Institute), in an accompanying News & Views article, speculates that the 'first' change might actually have arisen in response to a detrimental effect caused by the 'second', with the undesired consequence of bestowing greater susceptibility to malaria on carriers. These findings point out the complexities of the evolutionary relationship between host and parasite, and provide an example of how a gene variant that is beneficial under some conditions might prove harmful under others.