Alu family classification

The human specific Alu are further classified as sub families according to diagnostic nucleotide substitution along their sequence. Due to this characteristic, they can serve as unique evolutionary milestones. Phylogenetic studies of Alu elements suggest that only a small number of Alu elements deemed "master" or source genes are retropositionally competent, overtime the eventual accumulation of new mutations within the master or source genes created the hierarchy of Alu subfamilies. Diagnostic mutation sites can be used to classify each individual element according to subfamily. Alu classification is based upon age which is:

1. The oldest (J) 2. Intermediate (S) 3. Youngest (Y).

Some young Alu subfamilies have amplified so recently that they are virtually absent from the genome of nonhuman primates, as the result of the recent integration of young

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Alu subfamily members with in the human genome, individual human can be polymorphic for the presence of Alu element at particular loci. Almost all of the recently integrated human Alu elements belong to one of the several small and closely related young Alu subfamilies known as Y, Yel, Yc2, Ya5,Ya5a2, Ya8, Yb8, Yb9 and Yd (Roy-Angel et al. 2001 and Batzer et al. 1995).Although some newly integrated Alu elements result in detrimental mutation events in the human genome, 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 Alu-insertion polymorphisms are essentially homoplasy free characteristics that can be used to study human population genetics. 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 signature. By contrast, other types of genetic polymorphism, such as variable numbers of tandem repeats, RFLPs and single-nucleotide polymorphisms (SNPs), 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.

Alu insertion polymorphisms have several attractive features that make them unique elements for the study of human population genetics. First of all, the genotypes of Alu insertion polymorphisms are easy to determine by typing with rapid, nonradioactive, simple PCR based assays. They are biallelic polymorphisms with three possible genotypes: homozygous for the presence of the Alu element, heterozygous with one chromosome having the Alu element and the other lacking it and homozygous for the absence of the Alu element (Batzer et al. 1995).

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Figure 7

Expansion of recently integrated human Alu subfamilies.

Several subfamilies of Alu elements have expanded simultaneously in the human genome primarily from three Y-subfamily lineages, termed ‘Ya’, ‘Yb’ and ‘Yc’ in accordance with standard Alu nomenclature on the basis of commonly shared mutations. The approximate copy number of each subfamily is given as estimated from computational analysis of the draft sequence of the human genome. The percentage of insertion polymorphisms in each family is given In brackets. Alu subfamilies with smaller copy numbers and higher levels of insertion polymorphism are generally thought to be more recent in origin in the human genome (Batzer, 2002)

Secondly, once inserted into a new location, an Alu element is rarely subject to deletion. Even if deleted, it would not be an exact excision, but instead it would leave behind a molecular signature of the original insertion event by either retaining a part of the Alu element and/or deleting some of the flanking region (Novick et al.

1992).Therefore, Alu insertion polymorphisms are stable markers that reflect a unique evolutionary event, which is the insertion of an Alu element into a new chromosomal location.

Thirdly, Alu insertion polymorphisms display unique events that occurred during human evolution. Since there are 3 billion nucleotides in the haploid human genome, the probability that an Alu element would insert between the exact same two nucleotides at two different times during evolution is insignificant. Therefore, there is no parallel gain or loss of Alu elements at a particular chromosomal location, so all chromosomes that carry a polymorphic Alu element must be identical by descent.

Hence, polymorphic Alu insertions reflect population relationships more accurately than

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other genetic markers, such as RFLP, SNPs, STRs, microsatellites, mtDNA markers, etc. The disadvantage of these latter genetic markers lies in the fact that they have arisen as the result of several independent parallel mutations at different times. Therefore, they are identical by state rather than descent and thus may have not been inherited from a common ancestor. This is because the same allele could arise independently at different times during human evolution (Edwards et al. 1992).

Lastly, the ancestral state of Alu insertion polymorphisms is known to be the absence of the Alu element at a particular chromosomal location and the derived state is the presence of the Alu element. The precise knowledge of the ancestral state of a genomic polymorphism, which is very important in phylogenetic analyses, permits the construction of phylogenetic trees without making too many assumptions (Batzer et al.

2002; Batzer et al. 1994; Batzer et al. 1996a; Stoneking et al. 1997).

III- X Chromosome: properties and relevance in human identification and