Unformatted text preview: n. The expansion of the various Alu subfamilies is colour coded to denote the times of peak amplification. The approximate copy numbers of each Alu subfamily are also noted. Mya, million years ago. ORTHOLOGOUS GENES Loci in two species that are derived from a common ancestral locus by a speciation event. This is different from paralogous members of a gene family that are derived from duplication events.
GENETIC DRIFT Random changes in allele frequency that result from the sampling of gametes from generation to generation. they were polymorphic with respect to their presence or absence in diverse human genomes35,50–52. Almost all of the recently integrated human Alu elements belong to one of several small and closely related ‘young’ Alu subfamilies, known as Y, Yc1, Yc2, Ya5, Ya5a2, Ya8, Yb8 and Yb9 (REFS 35,44–46,52–55). With the exception of the Alu Y-family elements, and of a small number of elements from the other ‘young’ subfamilies43,56–58, individual members of these young Alu subfamilies that are present in the human genome are not found at ORTHOLOGOUS positions in the genomes of other great apes. These largely human-specific Alu subfamilies represent only ~0.5% of all the Alu repeats in the human genome and have amplified in the human genome in an overlapping time frame, as shown in FIG. 3. Although some newly integrated Alu elements result in detrimental mutation events in the human genome (see below), the vast majority of recently integrated Alu elements have had no apparent negative impact on the genome and represent new, essentially neutral, mutation events. After a new, neutral Alu insertion integrates into the genome, it is subjected to GENETIC DRIFT. So, the probability that it will be lost from the population is initially quite high, depending on the size of the population (the greater the population size, the more likely it is to be lost). But, over a short period of time, the Alu element will increase in frequency in the population. Because the amplification of Alu repeats is a continuing process, a series of Alu elements must have integrated into the ke y Bu (G sh ala b go ab )y Hu m an lm on 5 Mya 15 Mya 25 Mya 35 Mya ~55 Mya Dimeric phase The analysis of human Alu-insertion polymorphisms has been used to address several questions about human origins and demography59,60,62–71. In several instances, many types of genetic variation (such as mitochondrial DNA sequences or restriction-fragment length polymorphisms (RFLPs)) have been examined in overlapping, diverse human populations and have provided largely congruent results with respect to the history of the human population62,65,70. Alu-insertion polymorphisms have several characteristics that make them unique reagents for the study of human population genetics51,59–61. Individuals that share Alu-insertion polymorphisms have inherited the Alu elements from a common ancestor, which makes the Alu-insertion alleles identical by descent. The identical-by-descent nature of SINE insertions that are used in phylogenetic studies72–75 has previously been questioned76, and several examples of SINE insertions that have occurred at or near the same genomic region have recently been reported77,78. However, variation in the presence or absence of SINE insertions seems to be quite rare, and is a function of both evolutionary time and retrotransposition rate. This is particularly true with respect to Alu-insertion polymorphisms, as the probability of two independent Alu insertions occurring in the same genomic region in the human population, given the current rate of Alu retrotransposition and the relatively short evolutionary time frame that is involved, is essentially zero59,78. Therefore, N ATURE REVIEWS | GENETICS VOLUME 3 | MAY 2002 | 3 7 3 © 2002 Nature Publishing Group REVIEWS
Alu-insertion polymorphisms are essentially HOMOPLASYfree characteristics that can be used to study human population genetics59,78. In addition, there is no evidence for any type of process that specifically removes Alu elements from the genome; even when a rare deletion occurs, it leaves behind a molecular signature79. By contrast, other types of genetic polymorphism, such as variable numbers of tandem repeats80, RFLPs81 and single-nucleotide polymorphisms (SNPs)82–84, are merely identical by state; that is, they have arisen as the result of several independent parallel mutations at different times and have not been inherited from a common ancestor. Alleles that are identical by descent have been directly inherited from a common ancestor. Alleles that are identical by state have the same character state, but have not been inherited from a common ancestor. The ancestral state of Alu-insertion polymorphisms is known to be the absence of the Alu element at a particular genomic location51,59,60. Precise knowledge of the ancestral state of a genomic polymorphism allows us to draw trees of population relationships without making too many assumptions59,60,63,69.
Alu elements as insertion mutations An insertion of an Alu element might alter the transcription of a gene by changing the methylation status of its promoter, by disrupting its promoter or by introducing additional r...
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